Cleavage‐stage versus blastocyst‐stage embryo transfer in assisted reproductive technology

Demián Glujovsky; Andrea Marta Quinteiro Retamar; Cristian Roberto Alvarez Sedo; Agustín Ciapponi; Simone Cornelisse; Deborah Blake

doi:10.1002/14651858.CD002118.pub6

Transferencia de embriones en el estadio de división versus estadio de blastocisto en la tecnología de reproducción asistida

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Referencias adicionales

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Referencias de otras versiones publicadas de esta revisión

Ir a:

estudios incluidos
estudios excluidos
estudios a la espera de valoración
estudios en curso
otras referencias

Blake D, Jones G, Johnson NP, Olive D, Wilson ML. Cleavage stage versus blastocyst stage embryo transfer in assisted conception (In vitro fertilisation, Intracytoplasmic sperm injection). Cochrane Database of Systematic Reviews 2000, Issue 2. Art. No: CD002118. [DOI: 10.1002/14651858.CD002118]

Blake D, Proctor M, Johnson N, Olive D. Cleavage stage versus blastocyst stage embryo transfer in assisted conception. Cochrane Database of Systematic Reviews 2002, Issue 2. Art. No: CD002118. [DOI: 10.1002/14651858.CD002118]

Blake D, Proctor M, Johnson N, Olive D. Cleavage stage versus blastocyst stage embryo transfer in assisted conception. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No: CD002118. [DOI: 10.1002/14651858.CD002118.pub2]

Blake DA, Farquhar CM, Johnson N, Proctor M. Cleavage stage versus blastocyst stage embryo transfer in assisted conception. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No: CD002118. [DOI: 10.1002/14651858.CD002118.pub3]

Glujovsky D, Blake D, Farquhar C, Bardach A. Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database of Systematic Reviews 2012, Issue 7. Art. No: CD002118. [DOI: 10.1002/14651858.CD002118.pub4]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

estudios excluidos
estudios a la espera de clasificación
estudios en curso

Aziminekoo 2015

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Iran
Participants	Number of participants randomised: 118 Age: BS 34.9 and CS 35.1 Number of previous treatments: BS 3.7 and CS 3.1 Infertility duration: BS 10.3 and CS 8.5 years Prognosis: poor prognostic factors Inclusion criteria: infertile women with at least two previous failures of implantation Exclusion criteria: females aged more than 40 years old with severe untreated uterus abnormalities, and couples with severe male factor infertility, such as severe oligospermia
Interventions	BS group: N = 57 CS group (day 3): N = 61 Description of the cycles: Long protocol (down‐regulation with GnRH agonist and stimulation with rFSH) Injected oocytes were transferred to culture dish with cleavage medium (Sydney IVF cleavage medium, Cook Medical) In blastocyst group, on day 3, embryos were transferred to blastocyst medium (Sydney IVF blastocyst medium) for 48 h extended culture. Then, the day 5 embryos (blastocysts) were transferred to uterus. All embryo transfers were performed using the Sydney IVF catheter (K‐JETS‐7019‐SIVF; Cook Medical) To support luteal phase, all participants received progesterone suppository.
Outcomes	Clinical pregnancy rate Multiple pregnancy rate Miscarriage rate Cancellation
Notes

Brugnon 2010

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: France
Participants	Number of participants randomised: 107 Age: BS and CS: not stated Number of previous treatments: not stated Infertility duration: not stated Prognosis: good prognosis Inclusion criteria: if more than five oocytes were retrieved and three top‐quality embryos (4 blastomeres, < 20% fragmentation without multinuclear blastomeres) were observed at day two, the couples were included in the study. Exclusion criteria: Not described
Interventions	BS group: N = 52 CS group (day 3): N = 56 Description of the cycles: Sequential media was used in both groups. The freezing method was standard slow freezing method at day 3(FreezeKit, Vitrolife) and at day 5/6 (G‐ FreezeKit Blast, Vitrolife)
Outcomes	Cumulative pregnancy rate Clinical pregnancy rate per embryo transfer
Notes

Bungum 2003

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Denmark
Participants	Number of participants randomised: 118 Age: BS 31.2 and CS 31.3 Number of previous treatments: not stated Infertility duration: not stated Prognosis: good prognosis patients Inclusion criteria: D3 3 or more 8‐cell embryos < 20% fragmentation, eligible participants under 40 years of age, BMI < 30, FSH < 12 Exclusion criteria: not stated
Interventions	BS group: N = 61 CS group (day 3): N = 57 Description of the cycles: Long protocol (down‐regulation with GnRH agonist and stimulation with rFSH) HEPES‐buffered medium, was used to rinse the oocytes(Vitrolife, Gothenburg,Sweden) Embryos cultured for either 3 or 5 days in the sequential media system used in the standard IVF/ICSI programme (G1/G2 Vitrolife, Gothenburg, Sweden). All embryo transfers were performed with a Cook Soft 5000catheter (Cook, Australia) To support luteal phase, all participants received progesterone suppository
Outcomes	Clinical pregnancy rate Multiple rate Miscarriage Embryo freezing rate Implantation rate
Notes	3 or more 8‐celled D3 Lower blast rate in ICSI than IVF Letter sent and reply received

Coskun 2000

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Israel
Participants	Number of participants randomised: 201 Age: BS 30.4 and CS 30.7 Number of previous treatments: not stated Infertility duration: not stated Prognosis: good prognosis Inclusion criteria: all IVF/ICSI cycles from consenting patients with four or more fertilized oocytes. Exclusion criteria: no exclusion criteria
Interventions	BS group: N = 100 CS group (day 3): N = 101 Description of the cycles: Long protocol (down‐regulation with GnRH agonist and stimulation with rFSH) IVF medium(Medi‐Cult) was used to rinse the oocytes. Embryos cultured for day 3 were cultured in IVF medium(Medi‐cult). Embryos for day 5 were cultured in the sequential media system (G1/G2 Vitrolife, Gothenburg, Sweden). To support luteal phase, all participants received progesterone suppository(100mg/daily i.m)
Outcomes	Clinical pregnancy rate Multiple pregnancy rate High‐order multiple pregnancy rate Miscarriage rate
Notes	Prognosis: good 4 or more zygotes Young women Good ET policy Mixture of media brands Low blast rate High implantation rate considering No dropouts unusual

Devreker 2000

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Belgium
Participants	Number of participants randomised: 23 Age: not stated Number of previous treatments: not stated Infertility duration: not stated Prognosis: poor prognostic Inclusion criteria: age < 40 years old and > four previous cycles Exclusion criteria: not stated
Interventions	BS group: N = 11 CS group (day 2): N = 12 Description of the cycles: not stated
Outcomes	Live birth rate Clinical pregnancy rate Miscarriage rate
Notes	Prognosis: poor Abstract only Letter sent regarding randomisation

Elgindy 2011

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Egypt
Participants	Number of participants randomised: 200 Age: BS 28.47 and CS 27.7 Number of previous treatments: not stated Infertility duration: BS 6.22 and CS 6.84 years Prognosis: not stated Inclusion criteria: participants under 35 years of age, with regular cycles, serum day‐3 FSH concentration < 9.5 IU/L and antral follicle count > 6. At least four good‐quality embryos on day 3 Exclusion criteria: not described
Interventions	BS group: N = 100 CS group (day 2): N = 100 Description of the cycles: Long protocol (down‐regulation with GnRH agonist and stimulation with rFSH and HCG) Embryos were cultured in sequential media (Sage; Cooper Surgical, USA)
Outcomes	Live birth rate per fresh embryo transfer Clinical pregnancy rate Miscarriage rate Failure rate to transfer embryos
Notes

Emiliani 2003

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Belgium
Participants	Number of participants randomised: 171 Age: BS 32 and CS 31 Number of previous treatments: BS 2.0 and CS 1.7 Infertility duration: not stated Prognosis: mixed unselected Inclusion criteria: participants under 39 years of age, 3 or fewer previous cycles, 4 or more 2PN on day 1 Exclusion criteria: not described
Interventions	BS group: N = 82 CS group (day 2): N = 89 Description of the cycles: Ovarian stimulation was performed using GnRH analogue (buserelin acetate: Suprefact spray; Hoechst, Germany), hMG (Humegon; Organon, The Netherlands) and hCG (Pregnyl; Organon). For culture between day 3 and day 5 after insemination, similar dishes were prepared, containing blastocyst medium (in‐house sequential media).
Outcomes	Live birth rate per fresh embryo transfer Cumulative pregnancy rate Clinical pregnancy rate Multiple pregnancy rate Failure rate to transfer embryos
Notes	Prognosis: mixed unselected Outcome: discontinued blast culture Gives cumulative fresh thawed rates Not all different women ‐ per cycle data only

Fernandez‐Shaw 2015

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Spain
Participants	Number of participants randomised: 120 Age: BS 35.2 and CS: 36.3 Number of previous treatments: BS 0 and CS 0 Infertility duration: BS 23.9 months and CS 27.7 months Prognosis: mixed unselected Inclusion criteria: first IVF or ICSI cycle; presence of normal uterine cavity; ejaculated sperm origin; absence of any contraindications to pregnancy Exclusion criteria: oocyte donation cycles; vitrified oocytes cycles; non‐ejaculated sperm; PGD
Interventions	BS group: N = 60 CS group (day 3): N = 60 Description of the cycles: Three ovarian stimulation protocols were used for the 120 participants in the study depending on their age and diagnosis: long GnRH agonist protocol with intranasal nafarelin; short GnRH agonist protocol with nafarelin; GnRH antagonist protocol where the ganirelix was started on day 6 of the stimulation. All with recombinant daily FSH. Some participants were given added hMG when needed. Oocytes and embryos were cultured in sequential media of Vitrolife Sweden (G5 series, Kungsbacka, Sweden) using IVF, G1 and G2 medium as recommended by the manufacturer. All embryo transfers were performed using a Wallace catheter with EmbryoGlue media. To support luteal phase, all participants received progesterone suppository. Frozen embryos were vitrified in the day 3 and day 5 groups respectively. The vitrification followed the Irvine Scientific procedure.
Outcomes	Cumulative live birth rate* Live birth rate* Cumulative pregnancy rate Clinical pregnancy rate Multiple pregnancy rate Miscarriage rate The percentage of participants with embryos that were vitrified Three participants from the day 3 group and 2 from the day 5 group (with a mean number of 3 vitrified embryos) had not done a frozen embryo transfer cycle at the time of closing our interim analysis.
Notes	*Additional unpublished data received from contact author May 2016 in personal communication (email) to Demián Glujovsky. This is source of data on live births (analysis 1.1)

Fisch 2007

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: USA
Participants	Number of participants randomised: 20 Age: BS 31.2 and CS: 31.3 Number of previous treatments: BS 0 and CS 0 Infertility duration: BS 23.9 months and CS 27.7 months Prognosis: good prognosis Inclusion criteria: women under 41 years of age, with ≤ 2 prior fresh cycles with at least one embryo on day 3 with graduated embryo score ≥ 70 and soluble human leukocyte antigen‐G (sHLA‐G): 0.148–0.210 Exclusion criteria: not described
Interventions	BS group: N = 12 CS group (day 3): N = 8 Description of the cycles: not stated
Outcomes	Clinical pregnancy rate
Notes

Frattarelli 2003

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Hawaii
Participants	Number of participants randomised: 57 Age: BS 30.2 ± 3.2 and CS 31.0 ± 2.8 Number of previous treatments: BS 0 and CS 0 Infertility duration: not stated Prognosis: good prognosis Inclusion criteria: women under 35 years of age, no previous cycles, a day 3 FSH < 12 mIU/ml, ten or more follicles of 14mm or more on the day of hCG administration, and six or more high‐grade embryos on day 3 Exclusion criteria: not described
Interventions	BS group: N = 26 CS group (day 3): N = 23 Description of the cycles: In both groups they used the same media: sequential culture media. More information about the cycle is not available.
Outcomes	Live birth rate per fresh embryo transfer Clinical pregnancy rate Multiple pregnancy rate Miscarriage rate Failure rate to transfer embryos
Notes	Prognosis: good 6 or more high‐grade embryos D3, 1st cycle, young, high numbers of oocytes No dropouts due to lack of blasts High blast implantation rate

Gaafar 2015

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Egypt
Participants	Number of participants randomised: 326 Age: not stated Number of previous treatments: not stated Infertility duration: not stated Prognosis: unselected Inclusion criteria: couples suffering from male infertility, with indication for ICSI Exclusion criteria: not described
Interventions	BS group: N = 126 CS group (day 2): N = 126 Description of the cycles: Long agonist protocol was used followed by ICSI procedure. More information about the cycle is not available.
Outcomes	Clinical pregnancy rate Miscarriage rate
Notes

Gardner 1998a

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: USA
Participants	Number of participants randomised: 92 Age: BS 33.6 and CS 34.5 Number of previous treatments: BS 0.61 and CS 0.21 Infertility duration: not stated Prognosis: good prognosis patients Inclusion criteria: the female age must be under 45 years of age, FSH < 15 mIU/ml, presence of normal uterine cavity, adequate semen for IVF or ICSI. In addition, at least 10 follicles 12 or more mm in diameter were required on day of hCG trigger Exclusion criteria: any contraindications for pregnancy
Interventions	BS group: N = 45 CS group (day 3): N = 47 Description of the cycles: Ovarian hyperstimulation was initiated with leuprolide acetate. Embryos were cultured until day 3 in Ham's F10+ (Flow Laboratories,McLean, VA,USA) fetal cord serum (FCS), until D5 in Vitrolife G1 /G2 All embryo transfers were performed using a Wallace catheter (Edwards‐Wallance catheter; Marlow Technologies) To support luteal phase, all participants received steroids and tetracycline for 4 days post‐OPU and progesterone suppository, 50 mg IM in oil.
Outcomes	Clinical pregnancy rate Embryo freezing rate Implantation rate
Notes	Prognosis: good < 1 previous cycle and > 10 follicles Different media used for each arm of study Excluded participants not mentioned 'Number of ET' policy change partway through Unblinded interim analysis: initially participants received three blastocysts.

Hatirnaz 2017

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Turkey
Participants	Number of participants randomised: 201 Age: BS 30.4 and CS 29.4 Number of previous treatments: not stated Infertility duration: BS 8.1 and CS 7.8 years Prognosis: unselected participants Inclusion criteria: the retrieval of at least four fertilized oocytes was set up as a criterion for eligibility to keep the risk for treatment discontinuation and cycle cancellation at a minimum. Exclusion criteria: high risk for ovarian hyperstimulation.
Interventions	BS group: N = 95 CS group (day 3): N = 95 Description of the cycles: Long protocol (down‐regulation with GnRH agonist and stimulation with rFSH) Embryos for day 3 were cultured in the standard culture medium, blastocysts for day 5 were moved into G1.2 and G2.2 media (Scandinavian IVF Sciences, Gothenburg, Sweden) on day 1 and day 3, respectively. The luteal phase was supported by 50 mg intramuscular progesterone in oil once daily (Progestan®, Koçak Farma, İstanbul, Turkey) and estradiol, two 100 µg transdermal patches (Estraderm TTS®, Novartis Pharma AG, Basel, Sweden) with daily replacements.
Outcomes	Live birth rate Clinical pregancy rate Miscarriage rate Multiple rate Implantation rate
Notes

Hreinsson 2004

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Sweden
Participants	Number of participants randomised: 144 Age: BS 32.1 and CS 33.1 Number of previous treatments: not stated Infertility duration: not stated Prognosis: good; excluded poor responders Inclusion criteria: women undergoing IVF or ICSI treatment cycles, who had at least six follicles as observed at the final ultrasound scan before hCG administration were allocated to the study, after they had given informed consent. Exclusion criteria: not described
Interventions	BS group: N = 64 CS group (day 3): N = 80 Description of the cycles: Long protocol (down‐regulation with GnRH agonist and stimulation with rFSH) or short protocol with Cetrorelix Injected oocytes were collected into IVF‐medium (Vitrolife, Gothenburg, Sweden). The embryos were cultured from day 1 to day 3 in IVF‐medium and from D3 to D5‐6 in CCM‐medium'(Vitrolife). In the first 50 cases, sequential media was used( G1/G2 Vitrolife).
Outcomes	Clinical pregnancy rate
Notes	Prognosis: good; excluded poor responders Mixture of media types and ET policy change over course of study Outcome no advantage of blast culture Letter sent and reply received

Karaki 2002

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Jordan
Participants	Number of participants randomised: 162 Age: BS 30.0 and CS 29.0 Number of previous treatments: BS 0.9 and CS 1.1 Infertility duration: BS 6.8 and CS 6.7 years Prognosis: unselected participants Inclusion criteria: all patients needed at least five two‐pronuclei embryos. Exclusion criteria: not described
Interventions	BS group: N = 80 CS group (day 3): N = 82 Description of the cycles: Ovarian stimulation with GnRH agonist administrated in either long (down‐regulation) or short(flare) protocol in addition to HP‐FSH or recFSH. Embryos in the day 3 group were cultured in IVF medium (Medi‐Cult, Jyllinge, Denmark). Embryos for the blastocyst group were transferred to G1.2 and G2.2 media(Scandinavian IVF Sciences, Gothenburg, Sweden). All embryo transfers were performed using the Edward‐Wallace catheter. To support luteal phase, all participants received progesterone suppository.
Outcomes	Clinical pregnancy rate Multiple rate Miscarriage rate Failure rate to transfer embryos Implantation rate
Notes	Prognosis: moderate, young women, moderately high oocyte numbers. Large difference in embryo ET# between groups Sent letter

Kaser 2017

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: USA
Participants	Number of participants randomised: 163 Age: BS 34.4 and CS 34.6 years Number of previous treatments: not stated Infertility duration: not stated Prognosis: good prognosis Inclusion criteria: all participants aged 18 to 40 years with a planned fresh single embryo transfer Exclusion criteria: more than three prior retrievals without an intervening clinical pregnancy; use of donor oocytes, a gestational carrier, PGD, or in‐vitro maturation; and presence of uninterrupted hydrosalpinx or intrauterine adhesions. Participants were excluded if all embryos were frozen due to ovarian hyperstimulation, or if they had fewer than four zygotes.
Interventions	BS group: N = 107 CS group (day 3): N = 56 Description of the cycles: Three groups. D3 + time‐laps system/ D5 + time laps system/ D5 conventional. After fertilisation check, zygotes were placed in a 12 well Eeva dish(Global total with HSA, LifeGlobal, CT, USA) within a time‐lapse system.
Outcomes	Clinical pregnancy rate Cumulative pregnancy rate was not evaluated as the randomization was broken after the first transfer, and all embryos were cryopreserved at the blastocyst stage.
Notes	This study was funded by Progyny, Inc, which participated in the initial study design and approved the final embryo selection algorithms. All data handling, statistical analyses, and interpretation was performed independent of Progyny. The sponsor solely provided comments on the manuscript, and did not have editorial control in the manuscript preparation or submission. The trial was terminated prematurely in February 2016 by the sponsor due to a change in funding priorities. Enrolment opened in August 2014 and closed in February 2016. Clinicaltrials.gov NCT02218255

Kaur 2014

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: India
Participants	Number of participants randomised: 300 Age: BS 32.0 and CS: 34.4 Number of previous treatments: not stated Infertility duration: BS 7.7 and CS 8.9 years Prognosis: good prognosis group Inclusion criteria: participants aged 25‐40 years with 2‐20 years of infertility; having minimum five oocytes at oocyte pick up and endometrial thickness of 7 mm and more indicating good ovarian response; having normal uterine cavity and basal FSH < 10 mIU/mL; availability of minimum three good quality embryos Exclusion criteria: not described
Interventions	BS group: N = 150 CS group (day 3): N = 150 Description of the cycles: Long protocol (down‐regulation with GnRH agonist and stimulation with rFSH) Retrieved oocytes were incubated in IVF‐30 media. The fertilised oocytes were transferred into cleavage medium. In the blastocyst group extended culture till day 5 in G2 plus media. All transfers were performed using Edward–Wallace catheter. Luteal support was given in the form of micronised vaginal progesterone in dose of 200 mg twice a day. Injection HCG 2000 IU was given IM on days 5th, 8th, and 11th after retrieval
Outcomes	Clinical pregnancy Multiple pregnancy Miscarriage rate Implantation rate
Notes	Attempt to contact authors for more details of randomisation methods was not successful

Kolibianakis 2004

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Belgium
Participants	Number of participants randomised: 460 Age: BS 31.5 and CS 31.1 years Number of previous treatments: BS 0.8 and CS 0.7 Infertility duration: not stated Prognosis: unselected participants Inclusion criteria: women under 43 years of age and an indication for IVF Exclusion criteria: preimplantation genetic screening and azoospermia.
Interventions	BS group: N = 226 CS group (day 3): N = 234 Description of the cycles: Two ovarian stimulation protocols were used in the present study. Initially, the long protocol (down‐regulation with GnRH agonist and stimulation with rFSH). A combination of GnRH antagonist and recombinant gonadotropins was introduced in turn, and gradually replaced the long agonist protocol. Embryos were cultured in sequential media G1/G2 (Vitrolife, Goethenburg,Sweden). To support luteal phase, all participants received progesterone suppository.
Outcomes	Clinical pregnancy rate Miscarriage rate Embryo freezing rate Failure to transfer embryos
Notes	Prognosis: mixed unselected

Levi‐Setti 2018

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Italy
Participants	Number of participants randomised: 388 Age: BS 33.5 and CS 33.4 years Number of previous treatments: BS 2.05 and CS 2.06 Infertility duration: BS 3.96 and CS 4.42 years Prognosis: good prognosis Inclusion criteria: couples with a diagnosis of primary or secondary infertility with a clinical indication for IVF/intracytoplasmic sperm injection (ICSI), and under 39 years of age were enrolled, if they had more than three fertilised oocytes (zygotes) the day after insemination/injection. Exclusion criteria: couples with three or more failed previous IVF/ICSI cycles. Couples involved in other clinical or embryological trials or at high risk for ovarian hyperstimulation syndrome (OHSS) were also excluded.
Interventions	BS group: N = 188 CS group (day 3): N = 188 Description of the cycles: All enrolled patients underwent a stimulation treatment for IVF/ICSI. For patients in the cleavage stage group, two embryos were transferred, while for the ones in the blastocyst group, two blastocysts were transferred, when available. Embryo transfer was performed under ultrasound guidance using a soft catheter by a professional with at least 6 months of training
Outcomes	Live birth rate Clinical pregnancy rate Multiple pregnancy rate Miscarriage rate Implantation rate
Notes

Levitas 2004

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Israel
Participants	Number of participants randomised: 54 Age: BS 29.1 years and CS:31.2 years Number of previous treatments: BS 4.9 and CS 4.3 Infertility duration: BS 7.1 and CS 7.0 years Prognosis: Poor prognosis, multiple IVF failures Inclusion criteria: females aged younger than 37 years who were being treated mainly for tubal or male infertility, who had evidence of a normal uterine cavity, and who had no contraindication to pregnancy. Exclusion criteria: women with poor response on previous IVF cycles (peak estradiol level below 500 pg/mL or retrieval of fewer than three oocytes). Also patients with embryo transfer from donor oocytes or frozen‐thawed embryos
Interventions	BS group: N = 23 CS group (day 2 or 3): N = 31 Description of the cycles: Long protocol (down‐regulation with GnRH agonist and stimulation with rFSH) In blastocyst group, embryos cultured according to the sequential media system: the first 72 hours of culture in G1.2 medium (IVF Science, Scandinavia) followed by G2.2 medium (Scandinavia IVF Science, Gothenburg, Sweden) to day 5–7. To support luteal phase, all participants received five injections of hCG1,250 U every other day starting 48 hours after oocyte retrieval or daily IM administration.
Outcomes	Live birth rate Clinical pregnancy rate Multiple pregnancy rate Miscarriage rate Failure rate to transfer embryos Implantation rate
Notes	Note: young women with large numbers of failed cycles Uneven number in each group Similar figures to the 2001 abstract Letter sent and reply received

Levron 2002

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Israel
Participants	Number of participants randomised: 90 Age: BS 30.9 years and CS 31.5 Number of previous treatments: not stated Infertility duration: not stated Prognosis: good prognosis Inclusion criteria: maternal age less than 38 years, fewer than five previous IVF attempts, and presence of more than five zygotes on day 1 Exclusion criteria: not described
Interventions	BS group: N = 46 CS group (day 3): N = 44 Description of the cycles: Gamete and embryo handling procedures were done by using a commercial sequential IVF medium (Cook, Eight‐Miles Plains, Queensland, Australia).
Outcomes	Live birth rate Clinical pregnancy rate Multiple pregnancy rate Embryo freezing rate Failure to transfer emvryos Implantation rate
Notes	Prognosis: moderate Young women Moderately high numbers of oocytes Clarification letter sent Same ET policy

Livingstone 2002

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Australia
Participants	Number of participants randomised: 59 Age: BS 30 and CS 29 Number of previous treatments: not stated Infertility duration: BS 4.1 and CS 3.8 years Prognosis: good prognosis Inclusion criteria: participants under 38 years of age, 3 or fewer previous cycles Exclusion criteria: not described
Interventions	BS group: N = 30 CS group (day 3): N = 29 Description of the cycles: Long protocol (down‐regulation with GnRH agonist and stimulation with rFSH) All embryos were placed in media( Sydney IVF sequential) Fertilised oocytes were transferred to culture dish with cleavage medium (Sydney IVF cleavage medium, Cook Medical) To support luteal phase, all participants received progesterone suppository.
Outcomes	Live birth rate Clinical pregnancy rate Multiple pregnancy rate Miscarriage rate
Notes	Prognosis: good prognosis Data from thesis 2002 and not abstract 2001 Low fertilisation rate Aim to reduce twinning

Motta 1998

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Brazil
Participants	Number of participants randomised 83, in 116 cycles Age: not stated Number of previous treatments: not stated Infertility duration: not stated Prognosis: unselected participants Inclusion criteria: unselected Exclusion criteria: not described
Interventions	BS group: N = 58 CS group (day 2): N = 58 Description of the cycles: Long protocol (down‐regulation with GnRH agonist and stimulation with rFSH) The media used was sequential media P1 or Irvines Blast.
Outcomes	Clinical pregnancy rate Multiple pregnancy rate Embryo freezing rate Failure to transfer
Notes	Prognosis: moderate to good. No letter sent

Pantos 2004

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Greece
Participants	Number of participants randomised: 243 Age: BS 33.1 and CS D2 32.4; D3 31.3 Number of previous treatments: not stated Infertility duration: not stated Prognosis: unselected participants Inclusion criteria: primary infertility, fewer than 4 previous unsuccessful ART attempts. Female age under 41 years of age. Exclusion criteria: not described
Interventions	BS group: N = 81 CS group (day 3) N = 81 D2; N = 81 D3 Description of the cycles: Ovarian stimulation with long or short protocol, using GnRH agonist and rFSH. All oocytes and embryos were cultured in sequential media from Vitrolife (IVF‐20, G1.2, and G2.2; Scandinavian IVF Science AB, Goteborg, Sweden).
Outcomes	Clinical pregnancy rate Embryo freezing rate
Notes

Papanikolaou 2005

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Belgium
Participants	Number of participants randomised: 164 Age: BS 29.9 and CS 29.6 Number of previous treatments: BS 1.4 and CS 1.3 Infertility duration: BS 2.9 and CS 2.7 years Prognosis: good prognosis Inclusion criteria: female age ≤ 37 years; three or fewer previous treatments, FSH on day 3 of the cycle ≤ 12IU/ml, ejaculated sperm origin, IVF or ICSI cycles with having at least four good‐quality embryos on day 3 of embryo culture. Exclusion criteria: oocyte donation cycles; non‐ejaculated sperm (testicular sperm aspiration, fine needle aspiration, micro‐epididymal sperm aspiration, percutaneous epididymal sperm aspiration); and pre genetic screening.
Interventions	BS group: N = 80 CS group (day 3): N = 84 Description of the cycles: Long protocol (down‐regulation with GnRH agonist and stimulation with rFSH), or short protocol (stimulation with rFSH and start with GnRH antagonist) Oocytes and embryos were cultured in sequential media of Vitrolife Sweden AB, Kungsbacka, Sweden, (GII or GIII series). On the morning of day 3, embryos were transferred from cleavage medium to blastocyst medium.
Outcomes	Live birth rate Clinical pregnancy rate Miscarriage rate Multiple pregnancy rate Failure to transfer
Notes	Prognosis: high, 4 high‐quality embryos D3, young women Letter sent regarding concealment 100% ET rate

Papanikolaou 2006

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Belgium
Participants	Number of participants randomised: 351 Age: BS 30.5 and CS 30.4 Number of previous treatments: not stated Infertility duration: BS 3.7 and CS 3.5 years Prognosis: good prognosis Inclusion criteria: women under 36 years of age who were undergoing a first or second trial of in vitro fertilization or intracytoplasmic sperm injection, whose serum follicle‐stimulating hormone level on day 3 of the menstrual cycle was 12 IU per liter or less, and who were undergoing transfer of one embryo. Exclusion criteria: the use of preimplantation genetic diagnosis
Interventions	BS group: N = 176 CS group (day 3): N = 175 Description of the cycles: Short protocol with GnRH antagonist and stimulation with rFSH) On the morning of day 3, the embryos were removed from cleavage medium and placed in blastocyst medium (sequential medium). To support luteal phase, all participants received progesterone suppository.
Outcomes	Live birth rate Clinical pregnancy rate Multiple pregnancy rate Miscarriage rate Embryo freezing rate Failure to transfer embryos
Notes	Prognosis: high, young women Letter sent regarding concealment, media and freezing

Rienzi 2002

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Italy
Participants	Number of participants randomised: 98 Age: BS 32.2 and CS 31.6 Number of previous treatments: not stated Infertility duration: not stated Prognosis: good prognosis Inclusion criteria: couples with female age of <38 years who were treated by ICSI and who had ≥ 8 two‐pronucleated zygotes on the day following ICSI. Exclusion criteria: not described
Interventions	BS group: N = 50 CS group (day 3): N = 48 Description of the cycles: Long protocol (down‐regulation with GnRH agonist and stimulation with rFSH) Normally fertilized oocytes (zygotes) were cultured in G1.2 medium up to day 3 after ICSI and in G.2.2 medium (both media purchased from Vitrolife) from day 3 to day 5 where applicable. Day 3 and day 5 embryo cryopreservation was performed with freeze‐kit 1 and freeze‐kit 2 (both purchased from Vitrolife) respectively, according to the manufacturer's instructions. To support luteal phase, all participants received progesterone suppository.
Outcomes	Live birth rate Clinical pregnancy rate Miscarriage rate Multiple pregnancy rate Embryo freezing rate Failure to transfer embryos
Notes	Prognosis: good; > 8 zygotes Letter sent and reply received

Schillaci 2002

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Italy
Participants	Number of participants randomised: 110 Age: not stated Number of previous treatments: not stated Infertility duration: not stated Prognosis: unselected participants Inclusion criteria: indication for ICSI treatment, with eight or more metaphase II oocytes and at least three zygotes Exclusion criteria: not described
Interventions	BS group: N = 60 CS group (day 3): N = 60 Description of the cycles: The media used in the CS group was IVF‐20, media used in the BS group was G1‐G2(Vitrolife)
Outcomes	Clinical pregnancy rate
Notes	Prognosis: unclear Abstract only

Singh 2017

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: NA
Participants	Number of participants randomised: 438 Age: not stated Number of previous treatments: not stated Infertility duration: not stated Prognosis: good prognosis Inclusion criteria: participants under 40 years of age, if more than 6 oocytes were retrieved and three top quality embryos (6‐8 blastomeres & less than 20% fragmentation without multinucleation) were observed at day 2 Exclusion criteria: not described
Interventions	BS group: N = 243 CS group (day 3): N = 195 Description of the cycles: not described
Outcomes	Clinical pregnancy rate
Notes

Ten 2011

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Spain
Participants	Number of participants randomised: 55 Age: BS 33.4 and CS 33.1 Number of previous treatments: not stated Infertility duration: not stated Prognosis: good prognosis Inclusion criteria: women with on day three after ovarian punction at least one embryo type A and two type B, according to the ASEBIR classification Exclusion criteria: not described
Interventions	BS group: N = 28 CS group (day 3): N = 27 Description of the cycles: not described
Outcomes	Clinical pregnancy rate but cumulative pregnancy rate later Number of frozen embryos
Notes	Abstract only

Van der Auwera 2002

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: Belgium
Participants	Number of participants randomised: 136 Age: BS 31.5 and CS 31.7 Number of previous treatments: BS 1.7 and CS 1.7 Infertility duration: BS 3.4 and CS 3.3 years Prognosis: unselected participants Inclusion criteria: IVF and ICSI patients Exclusion criteria: not described
Interventions	BS group: N = 70 CS group (day 2): N = 66 Description of the cycles: Long protocol (down‐regulation with GnRH agonist and stimulation with rFSH) Oocytes and embryos were cultured in either sequential media from Cook (Fertilization, Cleavage and Blastocyst medium; Cook IVF, Queensland, Australia) or sequential media from Vitrolife (IVF‐500, G1.2 and G2.2, Scandinavian IVF Science AB, Göteborg, Sweden) Luteal supplementation was given either by 1500 IU HCG, every 3 days, starting on the third day after oocyte retrieval, or by vaginal progesterone (600 mg/day, Utrogestan^®; Piette International, Drogenbos, Belgium)
Outcomes	Live birth rate Cumulative clinical pregnancy rate Clinical pregnancy rate Multiple pregnancy rate Miscarriage rate Embryo freezing rate Failure to transfer embryos
Notes	Prognosis: mixed ‐ unselected Aim to reach highest cryoaugmented pregnancy rate Smaller cohort of embryos to choose from in D2 group due to freezing on day 1 New policy women with > 5 zygotes go to D5 transfer with 79% pregnancy rate

Yang 2018

*Study characteristics*
Methods	Study type: randomised controlled trial in parallel groups Country: China
Participants	Number of participants randomised: 600 Age: BS 28.0 and CS 28.3 Number of previous treatments: not stated Infertility duration: BS 3.8 and CS 3.8 years Prognosis: good prognosis Inclusion criteria: participants under 37 years of age, who were undergoing their first or second fresh IVF cycle using their own oocytes, and who had FSH levels ≤ 12 IU/mL on Day 3 of the cycle and 10 or more oocytes retrieved. IVF and ICSI patients Exclusion criteria: underlying uterine conditions including endometriosis, untreated unilateral or bilateral hydrosalpinx, and uterine myoma (multiple, submucous or intramural myoma > 3 cm), or had cycles planned for oocyte donation or PGD, or had recurrent pregnancy loss. Also people with significantly abnormal oocytes, or < 6 normally fertilised embryos (2PN) or who were considered unlikely to complete the study based on the investigator’s judgement.
Interventions	Conventional blastocyst stage: N = 300 TLS cleavage stage (day 3): N = 300 Description of the cycles: Ovarian stimulation protocols were carried out according to the subject’s ovarian reserve. All the oocytes were placed in fertilisation medium (G‐IVF; Vitrolife, Goteborg, Sweden)
Outcomes	Clinical pregnancy rate Multiple pregnancy rate Miscarriage rate
Notes

2PN: two‐pronuclear zygote
AHA: assisted hatching
ART: assisted reproductive technology
Blast: blastocyst
Blastocyst rate: number of blastocysts developed divided by number of 2PN embryos available
BMI: body mass index
BS: blastocyst stage
CS: cleavage stage
D2: embryo transfer on day 2 post‐OPU (i.e. early cleavage stage)
D3: embryo transfer on day 3 post‐OPU
D5: embryo transfer on day 5 post‐OPU (i.e. blastocyst stage)
ET: embryo transfer
FCS: foetal chord serum
FSH: follicle stimulating hormone
G1/G2: sequential media from Vitrolife
GnRH: gonadotropin‐releasing hormone
h: hour(s)
high‐order: high‐order multiple pregnancy
HCG: human chorionic gonadotropin (trigger injection that initiates ovulation and maturation of oocytes)
ICSI: intracytoplasmic sperm injection
IM: intramuscular injection
IU/L: international units per litre
IVF: in vitro fertilisation
MII: metaphase II
mIU/m: milli international units per millilitre
morula: embryonic stage prior to blastocysts (usually embryos with delayed development on day 5)
NS: not stated
OPU: oocyte pick up
Ov stim: ovarian stimulation regimen
PGD: preimplantation genetic diagnosis
rFSH: recombinant follicle stimulating hormone (fertility ovarian stimulation drug)
#: number
US: ultrasound

Characteristics of excluded studies [ordered by study ID]

Ir a:

estudios incluidos
estudios a la espera de clasificación
estudios en curso

Study	Reason for exclusion
Bungum 2002	Used co‐culture
Cornelisse 2018	Non‐RCT; letter to the editor
Green 2016	Ineligible study design: a retrospective cohort
Guerin 1991	Used co‐culture
Holden 2017	Ineligible study design: retrospective review
Levron 2001	Quasi‐randomised RCT
Loup 2009	Included transfer of embryos on two separate days within the same cycle
Menezo 1992	Used co‐culture
Utsonomiya 2004	Non‐randomised study (sequentially numbered)
Zech 2007	Non‐randomised study; according to even or odd year of birth

RCT: randomised controlled trial

Characteristics of studies awaiting classification [ordered by study ID]

Ir a:

estudios incluidos
estudios excluidos
estudios en curso

Clua Obrado 2020

Methods	Single center randomised controlled trial
Participants	Recipients between 18 and 50 years old in their first or second synchronous cycle Exclusion criteria: implantation failure and PGT‐A
Interventions	D3 or D5 embryo transfer
Outcomes	Clinical pregnancy rate and cumulative live birth rate
Notes	March 2017 ‐ August 2018 NCT 03088735 Barcelona, Spain The authors were contacted but they did not want to provide the missing information until the study was published in a peer‐reviewed journal.

PGT‐A: preimplantation genetic testing for aneuploidies

Characteristics of ongoing studies [ordered by study ID]

Ir a:

estudios incluidos
estudios excluidos
estudios a la espera de clasificación

ChiCTR‐ICR‐15006184

Study name	Cumulative live birth rates after cleavage‐stage versus blastocyst‐stage embryo transfer: a multicenter, prospective, randomized controlled trial
Methods	Study type: Randomised controlled trial in parallel groups Country: China
Participants	Number of participants to be randomised: 600 Age: 20 to 39 years old Number of previous treatments: NA Infertility duration: NA Prognosis: NA Inclusion criteria: infertility, ≥ 4 top‐quality embryos (≥ 8‐cell, < 20% fragments) Exclusion criteria:NA
Interventions	Blastocyst transfer group: extending embryo culture 2‐3 days in vitro to the blastocyst stage Cleavage transfer group: no intervention
Outcomes	Cumulative birth rates within one year; embryo freezing rate; cumulative pregnancy rate per woman; miscarriage rate; neonatal outcomes; monozygotic twinning; multiple pregnancy rate per transfer; live birth rate/per embryo
Starting date	May 2015
Contact information	Telephone:+86 025 68302608 Email: [email protected]
Notes	ChiCTR‐ICR‐15006184 Recruitment: From2018‐09‐29To 2019‐08‐31 Jiangsu, China

Cornelisse 2021

Study name	Three or Five Trial (ToF Trial)
Methods	For randomisation, all cases that subsequently meet all inclusion criteria will be randomised by the local laboratory staff, on the second day after fertilisation using the online software program Castor (V.2018.3.11, Castor Electronic Data Capture, Amsterdam, the Netherlands). Laboratory staff can access the online randomisation program using a unique password for this study. The laboratory staff is unable to access forthcoming random assignments prior to randomisation. Allocation to the cleavage‐stage embryo transfer arm or the blastocyst‐stage embryo transfer arm transfer will be based on a 1:1 randomisation with randomly selected block sizes of 2, 4 and 6 and stratification for age (≥ 36 years or < 36 years). Laboratory staff, clinicians and the participants cannot be blinded, due to the nature of the intervention. Participating clinicians, laboratory staff and investigators will not be able to access the randomisation sequence.
Participants	Women between 18 and 43 years of age, aiming to start an IVF treatment, are being selected for inclusion in this study. For inclusion and randomisation, at least four embryos should be available on culture day 2 (an embryo is defined as an oocyte with cell division on day 2 after insemination; ≥ three pronucleus embryos are excluded). A woman can participate in the study in her first, second or third IVF treatment, and can participate in only one treatment cycle. Women are excluded if they meet any of the following criteria: use of preimplantation genetic diagnosis or use of vitrified oocytes. No cycles with preimplantation genetic testing for aneuploidy will be part of this study as this procedure is not allowed in the Netherlands.
Interventions	(1) The control group, with embryo transfer on day 3 after oocyte retrieval and with cryopreservation of supernumerary good‐quality embryos on day 3 or 4 according to the local protocol and criteria, or (2) the intervention group, with embryo transfer on day 5 after oocyte retrieval with cryopreservation of supernumerary good‐quality embryos on day 5 or 6. Cryopreserved embryos on day 6 will only be transferred after all frozen–thawed embryo transfer(s) on day 5 have been transferred without an ongoing pregnancy.
Outcomes	The primary outcome is the cLBR per oocyte retrieval, which includes the results of the fresh and frozen–thawed embryo transfers. Endpoints of the study are live birth, no pregnancy leading to live birth after transfer of all available embryos or after a follow‐up time of 12 months after the oocyte retrieval.
Starting date	28 August 2018
Contact information	Ms Simone Cornelisse; simone.cornelisse@ radboudumc.nl
Notes	Netherlands Inclusions completed, results expected in 2023

ISRCTN48090543

Study name	Trial comparing blastocyst transfer with cleavage stage transfer in women with increased maternal age
Methods	Prospective randomised double‐blinded study
Participants	Inclusion criteria Female participants aged between 37 and 42 years undergoing an IVF/ICSI attempt at the GENERA Centre for Reproductive Medicine in Rome History of less than 3 failed IVF/ICSI cycles ≥ 6 MII retrieved Signed consent form
Interventions	Participants will be randomised on the day of ovum pick up by an independent operator to: 1. Blastocyst transfer: 1.1. Ovarian stimulation by agonist or antagonist protocol 1.2. Ovum pick up performed 36 hours after human chorionic gonadotropin (HCG) administration 1.3. In vitro fertilization performed by intracytoplasmic sperm injection (ICSI) 1.4. In vitro culture performed with sequential media in 6% CO2 and 5% O2 atmosphere 1.5. Embryo transfer on day 5 two best quality blastocyst. Remaining blastocyst preserved by vitrification procedure 1.6. Luteal support by progesterone 200 mg vaginally three times a day from oocyte retrieval plus one day 2. Cleavage stage transfer: 2.1. Ovarian stimulation by agonist or antagonist protocol 2.2. Ovum pick up performed 36 hours after human chorionic gonadotropin (HCG) administration 2.3. In vitro fertilization performed by intra‐cytoplasmic sperm injection (ICSI) 2.4. In vitro culture performed with sequential media in 6% CO2 and 5% O2 atmosphere 2.5. Embryo transfer on day 3 two best quality embryos. Remaining embryos preserved by vitrification procedure 2.6. Luteal support by progesterone 200 mg vaginally three times a day from oocyte retrieval plus one day
Outcomes	Cumulative live birth rate after blastocyst or cleavage stage strategy including pregnancies from fresh + cryoembryos transferred within 6 months after the end of the treatment
Starting date	01 November 2011
Contact information	Dr. Laura Rienzi: [email protected]
Notes

NCT01107002

Study name	Comparison of 5 day embryo transfer with 2‐3 day transfer in patients who failed to conceive in two or more day 2‐3 embryo transfer cycle in Royan Institute
Methods	Prospective randomised clinical trial divided into two groups. Random permuted blocks with a block size of 4 was used and complete allocation concealment Single‐blind (outcomes assessor)
Participants	200 participants with infertility Inclusion criteria: two or more previous failed IVF/ICSI cycles; 18 to 40 years
Interventions	Experimental: day 5 embryo transfer group Other group (day 2‐3) not described (only mentioned in the title and objectives)
Outcomes	Clinical pregnancy rate; live birth rate; implantation rate; miscarriage rate
Starting date	July 2008
Contact information	www.royaninstitute.org
Notes	Sponsor: Royan Institute Study completion date: August 2010 ClinicalTrials.gov ID: NCT01107002

NCT02639000

Study name	Effects of blastocyst stage embryo transfer compared with cleavage stage embryo transfer in women ≤ 38 years
Methods	Study type: randomised controlled trial in parallel groups Country: Italy
Participants	Number of participants to be randomised: 388 Age: 18 to 37 years Inclusion criteria: women with infertility undergoing an IVF cycle, with at least 4 fertilised eggs
Interventions	Experimental: blastocyst: embryo transfer of at maximum 2 embryos at blastocyst stage Active comparator: cleavage: embryo transfer of at maximum 2 embryos at cleavage stage
Outcomes	Pregnancy rate; multiple pregnancy rate; implantation rate
Starting date	July 2010
Contact information	Paolo Emanuele Levi‐Setti +39‐0282244505 [email protected]
Notes	Study completion: April 2016 Sponsor: Istituto Clinico Humanitas ClinicalTrials.gov ID: NCT02639000

NCT04210414

Study name	Cleave‐stage transfer on day 3 versus day 5 transfer when only one embryo available (Cleave‐blast)
Methods	Study type: interventional (clinical trial) Estimated enrollment: 1100 participants Allocation: randomised Intervention model: parallel assignment Masking: triple (care provider, investigator, outcomes assessor)
Participants	Inclusion criteria: infertile couple with only one embryo available for transfer
Interventions	Experimental: day 3 transfer Transfer on day 3 when only one embryo is available Experimental: day 5 transfer Transfer on day 5 when only one embryo is available
Outcomes	Ongoing pregnancy rate [Time frame: within 20 weeks of gestation]
Starting date	10 January 2020
Contact information	Muhammad Fawzy [email protected]
Notes

Neuhausser 2020

Study name	Day 3 vs Day 5 Embryo Transfer for Patients With Low Embryo Numbers Going Through in Vitro Fertilization
Methods	Phase 2. Allocation: dandomized Intervention model: parallel assignment Intervention model description: non‐inferiority Masking: none (open label) Primary purpose: treatment
Participants	18 to 44 years old Inclusion criteria First autologous IVF cycle Written, informed consent Exclusion Criteria Planned gestational carrier Planned donor egg Morbid obesity: BMI > 40 History of recurrent pregnancy loss (≥ 2 spontaneous abortions) Presence of uterine factor infertility Treatment plan includes embryos cultured 'out of protocol' Planned preimplantation genetic testing
Interventions	‐ uterine transfer of embryo on day 3 after fertilisation (cleavage stage) ‐ uterine transfer of embryo on day 5 after fertilisation (blastocyst stage) Procedure: day 3 uterine transfer Procedure: day 5 uterine transfer
Outcomes	Live birth [Time frame: 9 months] defined as delivery of a live born infant ≥ 22 weeks of gestation
Starting date	1 January 2021
Contact information	Werner Neuhausser, MD PhD (646) 510‐4825 [email protected]
Notes

PACTR201402000773124

Study name	Blastocyst versus day 2 transfer in low responders
Methods	Parallel: different groups receive different interventions at same time during study Randomised: permuted block randomisation (block size = 4) and the block size was not variable Sealed opaque envelopes
Participants	Inclusion criteria: poor response to ovarian stimulation as defined by European Society of Human Reproduction and Embryology (ESHRE) consensus (the Bologna criteria) (2011) Exclusion criteria: only one immature oocyte retrieve
Interventions	Blastocyst versus day 2 embryo transfer
Outcomes	Clinical pregnancy with cardiac pulsation
Starting date	25 June 2013
Contact information	[email protected]
Notes

PACTR201709002592834

Study name	A randomized controlled trial of pregnancy outcome of sequential versus day 3 and day 5 embryo transfer in cases with recurrent implantation failure
Methods	RCT: simple randomisation using a randomised table created by a computer software program Sealed opaque envelopes
Participants	Age 35 years or less Normal endometrial cavity on hysteroscopy Recurrent (2 or more) implantation failure Negative thrombophilia screening No hydrosalpinx No endometriosis Day 3 FSH < 10 IU/L and Estradiol < 80 pg/mL Antimullerian hormone 1‐3 ng/mL Availability of at least 5 embryos on postfertilisation check
Interventions	Day 3 vs day 5 embryo transfer
Outcomes	Live birth rate
Starting date	15 April 2015
Contact information	[email protected]
Notes

cLBR: cumulative live birth rate
FSH: follicle‐stimulating hormone
HCG: human chorionic gonadotropin
ICSI: intracytoplasmic sperm injection
IU: international units
IVF: in vitro fertilisation
LBR: live birth rate
MII: metaphase II
NA: not available

Riesgo de sesgo

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Risk of bias for analysis 1.1 Live birth per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 1.2 Live birth per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.2.1 More cleavage‐stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Subgroup 1.2.2 Single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 1.2.3 Equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 1.3 Live birth rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.3.2 poor prognostic factors
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 1.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.4 Live birth rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 1.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.4.3 randomised day 2 to 3 post‐OPU
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 1.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.

Open in table viewer

Risk of bias for analysis 2.1 Cumulative pregnancy rate from fresh and frozen transfers

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.2 Cumulative pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.2.1 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Subgroup 2.2.2 equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.3 Cumulative pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 2.3.2 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.4 Cumulative pregnancy rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.

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Risk of bias for analysis 2.5 Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.5.1 slow freezing
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.5.2 vitrification
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.

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Risk of bias for analysis 3.1 Clinical pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is some risk of bias due to the randomisation process, to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.2 Clinical pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.2.1 equal number of embryo transfers
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.2.2 more cleavage stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 3.2.3 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.3 Clinical pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.3.2 poor prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 3.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.4 Clinical pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.4.1 randomised start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 3.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 3.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.5 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.6 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus TLS (with algorithm) blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.1 Multiple pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.2 Multiple pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.2.1 equal number of embryos transferred
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.2.2 more cleavage stage than blastocyst embryos transferred
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 4.2.3 single embryo transfer
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.3 Multiple pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.3.1 good prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.3.2 poor prognostic factors
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 4.3.3 unselected
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.4 Multiple pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.4.1 randomised start of cycle
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 4.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 4.4.4 day of randomisation unstated
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.5 High‐order pregnancies (more than 2 gestational sacs) per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to randomisation process, deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.6 Multiple pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 5.1 Miscarriage rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to randomization process and selection of the reported result
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concearns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 6.1 Embryo freezing per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 7.1 Failure to transfer any embryos (per couple)

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.1 Live birth per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.2 Live birth per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.2.1 More cleavage‐stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Subgroup 1.2.2 Single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 1.2.3 Equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.3 Live birth rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.3.2 poor prognostic factors
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 1.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 1.4 Live birth rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 1.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.4.3 randomised day 2 to 3 post‐OPU
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 1.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.

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Risk of bias for analysis 2.1 Cumulative pregnancy rate from fresh and frozen transfers

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.2 Cumulative pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.2.1 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Subgroup 2.2.2 equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.3 Cumulative pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 2.3.2 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.4 Cumulative pregnancy rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.

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Risk of bias for analysis 2.5 Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.5.1 slow freezing
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.5.2 vitrification
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.1 Clinical pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is some risk of bias due to the randomisation process, to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.2 Clinical pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.2.1 equal number of embryo transfers
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.2.2 more cleavage stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 3.2.3 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.3 Clinical pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.3.2 poor prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 3.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.4 Clinical pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.4.1 randomised start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 3.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 3.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.5 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.6 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus TLS (with algorithm) blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.1 Multiple pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.2 Multiple pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.2.1 equal number of embryos transferred
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.2.2 more cleavage stage than blastocyst embryos transferred
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 4.2.3 single embryo transfer
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.3 Multiple pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.3.1 good prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.3.2 poor prognostic factors
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 4.3.3 unselected
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.4 Multiple pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.4.1 randomised start of cycle
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 4.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 4.4.4 day of randomisation unstated
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.5 High‐order pregnancies (more than 2 gestational sacs) per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to randomisation process, deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.6 Multiple pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 5.1 Miscarriage rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to randomization process and selection of the reported result
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concearns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 6.1 Embryo freezing per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 7.1 Failure to transfer any embryos (per couple)

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.1 Live birth per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.2 Live birth per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.2.1 More cleavage‐stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Subgroup 1.2.2 Single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 1.2.3 Equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.3 Live birth rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.3.2 poor prognostic factors
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 1.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.4 Live birth rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 1.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.4.3 randomised day 2 to 3 post‐OPU
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 1.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.

Open in table viewer

Risk of bias for analysis 2.1 Cumulative pregnancy rate from fresh and frozen transfers

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.2 Cumulative pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.2.1 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Subgroup 2.2.2 equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.3 Cumulative pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 2.3.2 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.4 Cumulative pregnancy rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.

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Risk of bias for analysis 2.5 Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.5.1 slow freezing
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.5.2 vitrification
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.

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Risk of bias for analysis 3.1 Clinical pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is some risk of bias due to the randomisation process, to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.2 Clinical pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.2.1 equal number of embryo transfers
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.2.2 more cleavage stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 3.2.3 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.3 Clinical pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.3.2 poor prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 3.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.4 Clinical pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.4.1 randomised start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 3.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 3.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.5 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.6 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus TLS (with algorithm) blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.1 Multiple pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.2 Multiple pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.2.1 equal number of embryos transferred
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.2.2 more cleavage stage than blastocyst embryos transferred
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 4.2.3 single embryo transfer
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.3 Multiple pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.3.1 good prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.3.2 poor prognostic factors
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 4.3.3 unselected
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.4 Multiple pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.4.1 randomised start of cycle
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 4.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 4.4.4 day of randomisation unstated
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.5 High‐order pregnancies (more than 2 gestational sacs) per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to randomisation process, deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.6 Multiple pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 5.1 Miscarriage rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to randomization process and selection of the reported result
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concearns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 6.1 Embryo freezing per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 7.1 Failure to transfer any embryos (per couple)

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.1 Live birth per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.2 Live birth per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.2.1 More cleavage‐stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Subgroup 1.2.2 Single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 1.2.3 Equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.3 Live birth rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.3.2 poor prognostic factors
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 1.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 1.4 Live birth rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 1.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.4.3 randomised day 2 to 3 post‐OPU
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 1.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.

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Risk of bias for analysis 2.1 Cumulative pregnancy rate from fresh and frozen transfers

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.2 Cumulative pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.2.1 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Subgroup 2.2.2 equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.3 Cumulative pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 2.3.2 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.4 Cumulative pregnancy rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.

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Risk of bias for analysis 2.5 Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.5.1 slow freezing
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.5.2 vitrification
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.

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Risk of bias for analysis 3.1 Clinical pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is some risk of bias due to the randomisation process, to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.2 Clinical pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.2.1 equal number of embryo transfers
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.2.2 more cleavage stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 3.2.3 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.3 Clinical pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.3.2 poor prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 3.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.4 Clinical pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.4.1 randomised start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 3.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 3.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.5 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.6 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus TLS (with algorithm) blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.1 Multiple pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.2 Multiple pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.2.1 equal number of embryos transferred
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.2.2 more cleavage stage than blastocyst embryos transferred
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 4.2.3 single embryo transfer
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.3 Multiple pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.3.1 good prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.3.2 poor prognostic factors
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 4.3.3 unselected
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.4 Multiple pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.4.1 randomised start of cycle
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 4.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 4.4.4 day of randomisation unstated
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.5 High‐order pregnancies (more than 2 gestational sacs) per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to randomisation process, deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.6 Multiple pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 5.1 Miscarriage rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to randomization process and selection of the reported result
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concearns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

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Risk of bias for analysis 6.1 Embryo freezing per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 7.1 Failure to transfer any embryos (per couple)

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 1.1 Live birth per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.2 Live birth per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.2.1 More cleavage‐stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Subgroup 1.2.2 Single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 1.2.3 Equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.3 Live birth rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.3.2 poor prognostic factors
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 1.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.4 Live birth rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 1.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.4.3 randomised day 2 to 3 post‐OPU
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 1.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.

Open in table viewer

Risk of bias for analysis 2.1 Cumulative pregnancy rate from fresh and frozen transfers

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.2 Cumulative pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.2.1 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Subgroup 2.2.2 equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.3 Cumulative pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 2.3.2 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.4 Cumulative pregnancy rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.

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Risk of bias for analysis 2.5 Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.5.1 slow freezing
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.5.2 vitrification
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.

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Risk of bias for analysis 3.1 Clinical pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is some risk of bias due to the randomisation process, to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.2 Clinical pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.2.1 equal number of embryo transfers
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.2.2 more cleavage stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 3.2.3 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.3 Clinical pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.3.2 poor prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 3.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.4 Clinical pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.4.1 randomised start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 3.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 3.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.5 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.6 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus TLS (with algorithm) blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.1 Multiple pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.2 Multiple pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.2.1 equal number of embryos transferred
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.2.2 more cleavage stage than blastocyst embryos transferred
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 4.2.3 single embryo transfer
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.3 Multiple pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.3.1 good prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.3.2 poor prognostic factors
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 4.3.3 unselected
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.4 Multiple pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.4.1 randomised start of cycle
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 4.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 4.4.4 day of randomisation unstated
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.5 High‐order pregnancies (more than 2 gestational sacs) per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to randomisation process, deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.6 Multiple pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 5.1 Miscarriage rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to randomization process and selection of the reported result
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concearns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 6.1 Embryo freezing per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 7.1 Failure to transfer any embryos (per couple)

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.1 Live birth per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.2 Live birth per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.2.1 More cleavage‐stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Subgroup 1.2.2 Single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 1.2.3 Equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.3 Live birth rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.3.2 poor prognostic factors
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 1.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 1.4 Live birth rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 1.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.4.3 randomised day 2 to 3 post‐OPU
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 1.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.

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Risk of bias for analysis 2.1 Cumulative pregnancy rate from fresh and frozen transfers

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 2.2 Cumulative pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.2.1 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Subgroup 2.2.2 equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.3 Cumulative pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 2.3.2 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 2.4 Cumulative pregnancy rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.

Open in table viewer

Risk of bias for analysis 2.5 Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.5.1 slow freezing
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.5.2 vitrification
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.1 Clinical pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is some risk of bias due to the randomisation process, to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.2 Clinical pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.2.1 equal number of embryo transfers
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.2.2 more cleavage stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 3.2.3 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.3 Clinical pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.3.2 poor prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 3.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.4 Clinical pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.4.1 randomised start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 3.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 3.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.5 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.6 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus TLS (with algorithm) blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.1 Multiple pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.2 Multiple pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.2.1 equal number of embryos transferred
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.2.2 more cleavage stage than blastocyst embryos transferred
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 4.2.3 single embryo transfer
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.3 Multiple pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.3.1 good prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.3.2 poor prognostic factors
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 4.3.3 unselected
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.4 Multiple pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.4.1 randomised start of cycle
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 4.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 4.4.4 day of randomisation unstated
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.5 High‐order pregnancies (more than 2 gestational sacs) per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to randomisation process, deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.6 Multiple pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 5.1 Miscarriage rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to randomization process and selection of the reported result
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concearns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 6.1 Embryo freezing per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 7.1 Failure to transfer any embryos (per couple)

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.1 Live birth per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.2 Live birth per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.2.1 More cleavage‐stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Subgroup 1.2.2 Single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 1.2.3 Equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.3 Live birth rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.3.2 poor prognostic factors
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 1.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 1.4 Live birth rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 1.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.4.3 randomised day 2 to 3 post‐OPU
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 1.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.

Open in table viewer

Risk of bias for analysis 2.1 Cumulative pregnancy rate from fresh and frozen transfers

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.2 Cumulative pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.2.1 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Subgroup 2.2.2 equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.3 Cumulative pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 2.3.2 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 2.4 Cumulative pregnancy rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.

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Risk of bias for analysis 2.5 Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.5.1 slow freezing
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.5.2 vitrification
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.

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Risk of bias for analysis 3.1 Clinical pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is some risk of bias due to the randomisation process, to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.2 Clinical pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.2.1 equal number of embryo transfers
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.2.2 more cleavage stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 3.2.3 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.3 Clinical pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.3.2 poor prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 3.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.4 Clinical pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.4.1 randomised start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 3.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 3.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 3.5 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 3.6 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus TLS (with algorithm) blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.1 Multiple pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.2 Multiple pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.2.1 equal number of embryos transferred
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.2.2 more cleavage stage than blastocyst embryos transferred
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 4.2.3 single embryo transfer
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 4.3 Multiple pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.3.1 good prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.3.2 poor prognostic factors
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 4.3.3 unselected
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.4 Multiple pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.4.1 randomised start of cycle
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 4.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 4.4.4 day of randomisation unstated
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.

Open in table viewer

Risk of bias for analysis 4.5 High‐order pregnancies (more than 2 gestational sacs) per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to randomisation process, deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

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Risk of bias for analysis 4.6 Multiple pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 5.1 Miscarriage rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to randomization process and selection of the reported result
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concearns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Open in table viewer

Risk of bias for analysis 6.1 Embryo freezing per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Open in table viewer

Risk of bias for analysis 7.1 Failure to transfer any embryos (per couple)

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Data and analyses

Open in table viewer

Comparison 1. Blastocyst‐ versus cleavage‐stage transfer: live birth rate following fresh transfer

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Live birth per couple Show forest plot	15	2219	Odds Ratio (M‐H, Fixed, 95% CI)	1.27 [1.06, 1.51]
Open in figure viewer Analysis 1.1 Comparison 1: Blastocyst‐ versus cleavage‐stage transfer: live birth rate following fresh transfer, Outcome 1: Live birth per couple
1.2 Live birth per couple: grouped by number of embryos transferred Show forest plot	15	2677	Odds Ratio (M‐H, Fixed, 95% CI)	1.30 [1.10, 1.53]
Open in figure viewer Analysis 1.2 Comparison 1: Blastocyst‐ versus cleavage‐stage transfer: live birth rate following fresh transfer, Outcome 2: Live birth per couple: grouped by number of embryos transferred
1.2.1 More cleavage‐stage than blastocyst embryos transferred	6	483	Odds Ratio (M‐H, Fixed, 95% CI)	1.51 [1.03, 2.22]
1.2.2 Single embryo transfer	2	458	Odds Ratio (M‐H, Fixed, 95% CI)	1.47 [0.98, 2.20]
1.2.3 Equal number of embryos transferred	9	1736	Odds Ratio (M‐H, Fixed, 95% CI)	1.21 [0.99, 1.47]
1.3 Live birth rate per couple: grouped by prognosis Show forest plot	15		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.3 Comparison 1: Blastocyst‐ versus cleavage‐stage transfer: live birth rate following fresh transfer, Outcome 3: Live birth rate per couple: grouped by prognosis
1.3.1 good prognostic factors	9	1514	Odds Ratio (M‐H, Fixed, 95% CI)	1.28 [1.04, 1.59]
1.3.2 poor prognostic factors	2	77	Odds Ratio (M‐H, Fixed, 95% CI)	2.05 [0.53, 7.96]
1.3.3 unselected group	4	628	Odds Ratio (M‐H, Fixed, 95% CI)	1.19 [0.86, 1.66]
1.4 Live birth rate: grouped by day of randomisation Show forest plot	15		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.4 Comparison 1: Blastocyst‐ versus cleavage‐stage transfer: live birth rate following fresh transfer, Outcome 4: Live birth rate: grouped by day of randomisation
1.4.1 randomisation at start of cycle	6	1207	Odds Ratio (M‐H, Fixed, 95% CI)	1.08 [0.84, 1.38]
1.4.2 randomised on day of OPU and day 1 after OPU	5	566	Odds Ratio (M‐H, Fixed, 95% CI)	1.16 [0.82, 1.65]
1.4.3 randomised day 2 to 3 post‐OPU	2	364	Odds Ratio (M‐H, Fixed, 95% CI)	2.17 [1.42, 3.33]
1.4.4 day of randomisation unstated	2	82	Odds Ratio (M‐H, Fixed, 95% CI)	1.71 [0.67, 4.39]

Open in table viewer

Comparison 2. Blastocyst‐ versus cleavage‐stage transfer: cumulative pregnancy rate following fresh and frozen transfer

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Cumulative pregnancy rate from fresh and frozen transfers Show forest plot	5	632	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.64, 1.22]
Open in figure viewer Analysis 2.1 Comparison 2: Blastocyst‐ versus cleavage‐stage transfer: cumulative pregnancy rate following fresh and frozen transfer, Outcome 1: Cumulative pregnancy rate from fresh and frozen transfers
2.2 Cumulative pregnancy rate per couple: grouped by number of embryos transferred Show forest plot	5	739	Odds Ratio (M‐H, Fixed, 95% CI)	0.88 [0.65, 1.18]
Open in figure viewer Analysis 2.2 Comparison 2: Blastocyst‐ versus cleavage‐stage transfer: cumulative pregnancy rate following fresh and frozen transfer, Outcome 2: Cumulative pregnancy rate per couple: grouped by number of embryos transferred
2.2.1 single embryo transfer	1	107	Odds Ratio (M‐H, Fixed, 95% CI)	0.84 [0.39, 1.79]
2.2.2 equal number of embryos transferred	5	632	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.64, 1.22]
2.3 Cumulative pregnancy rate per couple: grouped by prognosis Show forest plot	5	632	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.64, 1.22]
Open in figure viewer Analysis 2.3 Comparison 2: Blastocyst‐ versus cleavage‐stage transfer: cumulative pregnancy rate following fresh and frozen transfer, Outcome 3: Cumulative pregnancy rate per couple: grouped by prognosis
2.3.1 good prognostic factors	2	205	Odds Ratio (M‐H, Fixed, 95% CI)	0.54 [0.30, 0.98]
2.3.2 unselected group	3	427	Odds Ratio (M‐H, Fixed, 95% CI)	1.10 [0.74, 1.61]
2.4 Cumulative pregnancy rate: grouped by day of randomisation Show forest plot	5	632	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.64, 1.22]
Open in figure viewer Analysis 2.4 Comparison 2: Blastocyst‐ versus cleavage‐stage transfer: cumulative pregnancy rate following fresh and frozen transfer, Outcome 4: Cumulative pregnancy rate: grouped by day of randomisation
2.4.1 randomisation at start of cycle	3	414	Odds Ratio (M‐H, Fixed, 95% CI)	0.81 [0.54, 1.20]
2.4.2 randomised on day of OPU and day 1 after OPU	2	218	Odds Ratio (M‐H, Fixed, 95% CI)	1.06 [0.61, 1.83]
2.5 Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing Show forest plot	5		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.5 Comparison 2: Blastocyst‐ versus cleavage‐stage transfer: cumulative pregnancy rate following fresh and frozen transfer, Outcome 5: Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing
2.5.1 slow freezing	4	512	Odds Ratio (M‐H, Fixed, 95% CI)	0.69 [0.48, 0.99]
2.5.2 vitrification	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	2.44 [1.17, 5.12]

Open in table viewer

Comparison 3. Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Clinical pregnancy rate per couple Show forest plot	32	5821	Odds Ratio (M‐H, Fixed, 95% CI)	1.25 [1.12, 1.39]
Open in figure viewer Analysis 3.1 Comparison 3: Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer, Outcome 1: Clinical pregnancy rate per couple
3.2 Clinical pregnancy rate per couple: grouped by number of embryos transferred Show forest plot	32	7062	Odds Ratio (M‐H, Fixed, 95% CI)	1.26 [1.14, 1.38]
Open in figure viewer Analysis 3.2 Comparison 3: Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer, Outcome 2: Clinical pregnancy rate per couple: grouped by number of embryos transferred
3.2.1 equal number of embryo transfers	20	4434	Odds Ratio (M‐H, Fixed, 95% CI)	1.31 [1.16, 1.48]
3.2.2 more cleavage stage than blastocyst embryos transferred	12	1387	Odds Ratio (M‐H, Fixed, 95% CI)	1.07 [0.86, 1.33]
3.2.3 single embryo transfer	5	1241	Odds Ratio (M‐H, Fixed, 95% CI)	1.31 [1.04, 1.65]
3.3 Clinical pregnancy rate per couple: grouped by prognosis Show forest plot	32	5821	Odds Ratio (M‐H, Fixed, 95% CI)	1.25 [1.12, 1.39]
Open in figure viewer Analysis 3.3 Comparison 3: Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer, Outcome 3: Clinical pregnancy rate per couple: grouped by prognosis
3.3.1 good prognostic factors	19	3645	Odds Ratio (M‐H, Fixed, 95% CI)	1.25 [1.09, 1.43]
3.3.2 poor prognostic factors	3	195	Odds Ratio (M‐H, Fixed, 95% CI)	1.62 [0.84, 3.10]
3.3.3 unselected group	10	1981	Odds Ratio (M‐H, Fixed, 95% CI)	1.22 [1.01, 1.46]
3.4 Clinical pregnancy rate per couple: grouped by day of randomisation Show forest plot	32	5821	Odds Ratio (M‐H, Fixed, 95% CI)	1.25 [1.12, 1.39]
Open in figure viewer Analysis 3.4 Comparison 3: Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer, Outcome 4: Clinical pregnancy rate per couple: grouped by day of randomisation
3.4.1 randomised start of cycle	8	1759	Odds Ratio (M‐H, Fixed, 95% CI)	1.12 [0.92, 1.37]
3.4.2 randomised on day of OPU or day 1	13	2094	Odds Ratio (M‐H, Fixed, 95% CI)	1.19 [1.00, 1.42]
3.4.3 randomised on day 2 to 3	6	1275	Odds Ratio (M‐H, Fixed, 95% CI)	1.50 [1.19, 1.88]
3.4.4 day of randomisation unstated	5	693	Odds Ratio (M‐H, Fixed, 95% CI)	1.33 [0.98, 1.80]
3.5 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage Show forest plot	2	709	Odds Ratio (M‐H, Fixed, 95% CI)	1.41 [1.04, 1.90]
Open in figure viewer Analysis 3.5 Comparison 3: Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer, Outcome 5: Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage
3.6 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus TLS (with algorithm) blastocyst stage Show forest plot	1	110	Odds Ratio (M‐H, Fixed, 95% CI)	0.91 [0.43, 1.96]
Open in figure viewer Analysis 3.6 Comparison 3: Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer, Outcome 6: Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus TLS (with algorithm) blastocyst stage

Open in table viewer

Comparison 4. Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Multiple pregnancy rate per couple Show forest plot	22	4208	Odds Ratio (M‐H, Fixed, 95% CI)	1.12 [0.90, 1.38]
Open in figure viewer Analysis 4.1 Comparison 4: Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer, Outcome 1: Multiple pregnancy rate per couple
4.2 Multiple pregnancy rate per couple: grouped by number of embryos transferred Show forest plot	22	5159	Odds Ratio (M‐H, Fixed, 95% CI)	1.12 [0.91, 1.38]
Open in figure viewer Analysis 4.2 Comparison 4: Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer, Outcome 2: Multiple pregnancy rate per couple: grouped by number of embryos transferred
4.2.1 equal number of embryos transferred	14	3399	Odds Ratio (M‐H, Fixed, 95% CI)	1.29 [1.01, 1.65]
4.2.2 more cleavage stage than blastocyst embryos transferred	8	809	Odds Ratio (M‐H, Fixed, 95% CI)	0.75 [0.49, 1.13]
4.2.3 single embryo transfer	2	951	Odds Ratio (M‐H, Fixed, 95% CI)	1.22 [0.51, 2.91]
4.3 Multiple pregnancy rate per couple: grouped by prognosis Show forest plot	22	4208	Odds Ratio (M‐H, Fixed, 95% CI)	1.12 [0.90, 1.38]
Open in figure viewer Analysis 4.3 Comparison 4: Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer, Outcome 3: Multiple pregnancy rate per couple: grouped by prognosis
4.3.1 good prognostic factors	15	2904	Odds Ratio (M‐H, Fixed, 95% CI)	1.14 [0.89, 1.46]
4.3.2 poor prognostic factors	1	54	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.14, 5.81]
4.3.3 unselected	6	1250	Odds Ratio (M‐H, Fixed, 95% CI)	1.07 [0.71, 1.59]
4.4 Multiple pregnancy rate per couple: grouped by day of randomisation Show forest plot	22	4208	Odds Ratio (M‐H, Fixed, 95% CI)	1.12 [0.90, 1.38]
Open in figure viewer Analysis 4.4 Comparison 4: Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer, Outcome 4: Multiple pregnancy rate per couple: grouped by day of randomisation
4.4.1 randomised start of cycle	7	1704	Odds Ratio (M‐H, Fixed, 95% CI)	1.02 [0.71, 1.46]
4.4.2 randomised on day of OPU or day 1	9	1647	Odds Ratio (M‐H, Fixed, 95% CI)	1.05 [0.73, 1.52]
4.4.3 randomised on day 2 to 3	4	682	Odds Ratio (M‐H, Fixed, 95% CI)	1.71 [1.14, 2.56]
4.4.4 day of randomisation unstated	2	175	Odds Ratio (M‐H, Fixed, 95% CI)	0.21 [0.06, 0.70]
4.5 High‐order pregnancies (more than 2 gestational sacs) per couple Show forest plot	13	2335	Odds Ratio (M‐H, Fixed, 95% CI)	0.45 [0.18, 1.15]
Open in figure viewer Analysis 4.5 Comparison 4: Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer, Outcome 5: High‐order pregnancies (more than 2 gestational sacs) per couple
4.6 Multiple pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage Show forest plot	1	600	Odds Ratio (M‐H, Fixed, 95% CI)	1.59 [0.61, 4.17]
Open in figure viewer Analysis 4.6 Comparison 4: Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer, Outcome 6: Multiple pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Open in table viewer

Comparison 5. Blastocyst‐ versus cleavage‐stage transfer: miscarriage rate following fresh transfer

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Miscarriage rate per couple Show forest plot	21	4106	Odds Ratio (M‐H, Fixed, 95% CI)	1.24 [0.98, 1.57]
Open in figure viewer Analysis 5.1 Comparison 5: Blastocyst‐ versus cleavage‐stage transfer: miscarriage rate following fresh transfer, Outcome 1: Miscarriage rate per couple

Open in table viewer

Comparison 6. Blastocyst‐ versus cleavage‐stage transfer: embryo freezing rate per couple

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Embryo freezing per couple Show forest plot	14	2292	Odds Ratio (M‐H, Fixed, 95% CI)	0.48 [0.40, 0.57]
Open in figure viewer Analysis 6.1 Comparison 6: Blastocyst‐ versus cleavage‐stage transfer: embryo freezing rate per couple, Outcome 1: Embryo freezing per couple

Open in table viewer

Comparison 7. Blastocyst‐ versus cleavage‐stage transfer: failure rate to transfer embryos (per couple)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
7.1 Failure to transfer any embryos (per couple) Show forest plot	17	2577	Odds Ratio (M‐H, Fixed, 95% CI)	2.50 [1.76, 3.55]
Open in figure viewer Analysis 7.1 Comparison 7: Blastocyst‐ versus cleavage‐stage transfer: failure rate to transfer embryos (per couple), Outcome 1: Failure to transfer any embryos (per couple)

Figure 1

Study flow diagram: results of search from review inception to 2020 (update of the flow diagram published in 2016)

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Figure 2

Forest plot of comparison: 1 Blastocyst‐ versus cleavage‐stage transfer: live birth rate, outcome: 1.1 live birth per couple

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Figure 3

Forest plot of comparison: 2 Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy rate, outcome: 2.1 clinical pregnancy rate per couple

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Figure 4

Funnel plot of comparison: 1 Blastocyst‐ versus cleavage‐stage transfer: live birth rate, outcome: 1.1 live birth per couple

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Figure 5

Funnel plot of comparison: 2 Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy rate, outcome: 2.1 clinical pregnancy rate per couple

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Analysis 1.1

Comparison 1: Blastocyst‐ versus cleavage‐stage transfer: live birth rate following fresh transfer, Outcome 1: Live birth per couple

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Analysis 1.2

Comparison 1: Blastocyst‐ versus cleavage‐stage transfer: live birth rate following fresh transfer, Outcome 2: Live birth per couple: grouped by number of embryos transferred

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Analysis 1.3

Comparison 1: Blastocyst‐ versus cleavage‐stage transfer: live birth rate following fresh transfer, Outcome 3: Live birth rate per couple: grouped by prognosis

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Analysis 1.4

Comparison 1: Blastocyst‐ versus cleavage‐stage transfer: live birth rate following fresh transfer, Outcome 4: Live birth rate: grouped by day of randomisation

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Analysis 2.1

Comparison 2: Blastocyst‐ versus cleavage‐stage transfer: cumulative pregnancy rate following fresh and frozen transfer, Outcome 1: Cumulative pregnancy rate from fresh and frozen transfers

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Analysis 2.2

Comparison 2: Blastocyst‐ versus cleavage‐stage transfer: cumulative pregnancy rate following fresh and frozen transfer, Outcome 2: Cumulative pregnancy rate per couple: grouped by number of embryos transferred

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Analysis 2.3

Comparison 2: Blastocyst‐ versus cleavage‐stage transfer: cumulative pregnancy rate following fresh and frozen transfer, Outcome 3: Cumulative pregnancy rate per couple: grouped by prognosis

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Analysis 2.4

Comparison 2: Blastocyst‐ versus cleavage‐stage transfer: cumulative pregnancy rate following fresh and frozen transfer, Outcome 4: Cumulative pregnancy rate: grouped by day of randomisation

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Analysis 2.5

Comparison 2: Blastocyst‐ versus cleavage‐stage transfer: cumulative pregnancy rate following fresh and frozen transfer, Outcome 5: Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing

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Analysis 3.1

Comparison 3: Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer, Outcome 1: Clinical pregnancy rate per couple

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Analysis 3.2

Comparison 3: Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer, Outcome 2: Clinical pregnancy rate per couple: grouped by number of embryos transferred

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Analysis 3.3

Comparison 3: Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer, Outcome 3: Clinical pregnancy rate per couple: grouped by prognosis

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Analysis 3.4

Comparison 3: Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer, Outcome 4: Clinical pregnancy rate per couple: grouped by day of randomisation

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Analysis 3.5

Comparison 3: Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer, Outcome 5: Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

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Analysis 3.6

Comparison 3: Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer, Outcome 6: Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus TLS (with algorithm) blastocyst stage

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Analysis 4.1

Comparison 4: Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer, Outcome 1: Multiple pregnancy rate per couple

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Analysis 4.2

Comparison 4: Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer, Outcome 2: Multiple pregnancy rate per couple: grouped by number of embryos transferred

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Analysis 4.3

Comparison 4: Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer, Outcome 3: Multiple pregnancy rate per couple: grouped by prognosis

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Analysis 4.4

Comparison 4: Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer, Outcome 4: Multiple pregnancy rate per couple: grouped by day of randomisation

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Analysis 4.5

Comparison 4: Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer, Outcome 5: High‐order pregnancies (more than 2 gestational sacs) per couple

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Analysis 4.6

Comparison 4: Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer, Outcome 6: Multiple pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

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Analysis 5.1

Comparison 5: Blastocyst‐ versus cleavage‐stage transfer: miscarriage rate following fresh transfer, Outcome 1: Miscarriage rate per couple

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Analysis 6.1

Comparison 6: Blastocyst‐ versus cleavage‐stage transfer: embryo freezing rate per couple, Outcome 1: Embryo freezing per couple

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Analysis 7.1

Comparison 7: Blastocyst‐ versus cleavage‐stage transfer: failure rate to transfer embryos (per couple), Outcome 1: Failure to transfer any embryos (per couple)

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Summary of findings 1. Blastocyst‐stage versus cleavage‐stage embryo transfer for assisted reproductive technology

Outcomes per couple	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
Blastocyst‐stage versus cleavage‐stage embryo transfer for assisted reproductive technology
Population: women and couples with subfertility Settings: assisted reproductive technology Intervention: blastocyst‐stage embryo transfer Comparison: cleavage‐stage embryo transfer
	Assumed risk	Corresponding risk
	Cleavage‐stage embryo transfer	Blastocyst‐stage embryo transfer
Live birth rate per fresh transfer	312 per 1000	365 per 1000 (324 to 406)	OR 1.27 (1.06 to 1.51)	2219 (15 studies)	⊕⊕⊝⊝ Low^a,c	When sensitivity analysis restricted to 9 studies with low or some concerns of overall risk of bias, it results in a similar effect (OR 1.26, 95% CI 1.04 to 1.54).
Cumulative pregnancy rate (slow freezing)	565 per 1000	472 per 1000 (384 to 562)	OR 0.69 (0.48 to 0.99)	512 (4 studies)	⊕⊕⊝⊝ Low^a,c
Cumulative pregnancy rate (vitrification)	333 per 1000	550 per 1000 (369 to 719)	OR 2.44 (1.17 to 5.12)	120 (1 study)	⊕⊕⊕⊝ Moderate^a
Clinical pregnancy rate	390 per 1000	444 per 1000 (417 to 470)	OR 1.25 (1.12 to 1.39)	5821 (32 studies)	⊕⊕⊝⊝ Moderate^a	When sensitivity analysis restricted to 17 studies with low risk or some concerns of overall risk of bias, it results in a similar effect (OR 1.24, 95% CI 1.08 to 1.41).
Multiple pregnancy rate	89 per 1000	99 per 1000 (81 to 119)	OR 1.12 (0.90 to 1.38)	4208 (22 studies)	⊕⊕⊝⊝ Low^a,b,c	When sensitivity analysis restricted to 15 studies with low risk or some concerns of overall risk of bias, it results in an increase of multiple pregnancy rate (OR 1.33, 95% CI 1.04 to 1.70).
Miscarriage rate	67 per 1000	82 per 1000 (68 to 111)	OR 1.24, (0.98 to 1.57)	4106 (21 studies)	⊕⊕⊝⊝ Low^a,c
Embryo freezing rate	594 per 1000	412 per 1000 (369 to 455)	OR 0.48 (0.40 to 0.57)	2292 (14 studies)	⊕⊕⊝⊝ Low^a,b	I² = 84%. Direction of effect largely consistent
Failure rate to transfer any embryos	11 per 1000	26 per 1000 (19 to 37)	OR 2.50 (1.76 to 3.55)	2577 (17 studies)	⊕⊕⊕⊝ Moderate^a	I² = 36%
The basis for the assumed risk* is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; OR: odds ratio
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.
^aDowngraded one level for serious risk of bias: most studies have some concerns of overall risk of bias, mainly due to the randomisation process, deviations from the intended intervention and selective reporting ^bDowngraded one level for serious inconsistency ^cDowngraded one level for serious imprecision: findings compatible with benefit or minimal effect

Summary of findings 1. Blastocyst‐stage versus cleavage‐stage embryo transfer for assisted reproductive technology

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Table 1. Culture techniques of included studies

Trial	Culture technique day 2/3	Culture technique day 5/6
Aziminekoo 2015	Sydney IVF cleavage medium, Cook	Sydney IVF blastocyst medium
Brugnon 2010	G series™ medium (Vitrolife, Sweden)	G series™ medium (Vitrolife, Sweden)
Bungum 2003	Sequential G1 Vitrolife	Sequential G1/G2 Vitrolife
Coskun 2000	Sequential MediCult	Sequential G1/G2 Vitrolife
Devreker 2000	NS	NS
Elgindy 2011	NS	NS
Emiliani 2003	In‐house sequential (based on G1/G2)	In‐house sequential (based on G1/G2)
Fernandez‐Shaw 2015	Sequential G1 Vitrolife	Sequential G1/G2 Vitrolife
Fisch 2007	NS	NS
Frattarelli 2003	NS	NS
Gaafar 2015	NS	NS
Gardner 1998a	Single Ham's F10 In‐house	Sequential G1/G2 In‐house
Hatirnaz 2017	Standard culture medium	Sequential G1/G2 Scandinavian IVF Sciences
Hreinsson 2004	Vitrolife IVF	Sequential G1/G2 or CCM Vitrolife
Karaki 2002	MediCult	Sequential G1/G2 Vitrolife
Kaser 2017	Global total with HSA LifeGlobal	Global total with HSA LifeGlobal
Kaur 2014	Cleavage medium	G2 Plus media
Kolibianakis 2004	Sequential G1 Vitrolife	Sequential G1/G2 Vitrolife
Levi‐Setti 2018	NS	NS
Levitas 2004	NS	Sequential ‐ G1/G2 Vitrolife
Levron 2002	NS	NS
Livingstone 2002	Sequential ‐ Sydney IVF Cook	Sequential ‐ Sydney IVF Cook
Motta 1998	Sequential ‐ Irvines P1	Sequential ‐ Irvines P1 then Blast media
Pantos 2004
Papanikolaou 2005	Sequential ‐ Vitrolife G1/G2 GII or GIII	Sequential ‐ Vitrolife G1/G2 GII or GIII
Papanikolaou 2006	Assume sequential ‐ Vitrolife G1/G2	Assume sequential ‐ Vitrolife G1/G2
Rienzi 2002	Sequential G1 Vitrolife	Sequential G1/G2 Vitrolife
Schillaci 2002	NS	NS
Singh 2017	NS	NS
Ten 2011	NS	NS
Van der Auwera 2002	Sequential both Cook and Vitrolife	Sequential both Cook and Vitrolife
Yang 2018	Sequential media (G1.5, Vitrolife) in a Primo Vision time‐lapse system (Vitrolife)	Sequential G1/G2 Vitrolife
CCM: a Vitrolife trademarked medium for blastocyst culture IVF: in vitro fertilisation G1/G2:sequential media from Vitrolife NS: not stated

Table 1. Culture techniques of included studies

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Table 2. Blastocyst formation and implantation rate (in day 5 to 6 transfers)

Study	Blastocyst formation rate	Implantation D2/3	Implantation D5/6	Other
Aziminekoo 2015	22.4%	21/173; 12.1%	22/152; 14.5%
Brugnon 2010	Not stated	24/52; 46.2%	23/55; 41.8%
Bungum 2003	55.2%	50/114; 43.9%	44/120; 36.7%	2/61 participants had only 1 blastocyst
Coskun 2000	28%	50/235; 21.3%	52/218; 23.9%	77% participants had at least 1 blastocyst
Devreker 2000	Not stated	1/34; 2.9%	8/19; 42.1%
Elgindy 2011	97%	71/197; 36%	53/280; 19%
Emiliani 2003	48%	57/197; 28.9%	50/168; 29.8%
Fernandez‐Shaw 2015	67.7 %	20/71; 28.1%	36/84; 42.8%
Fisch 2007	Not stated	11/12; 92%	4/8; 50%
Frattarelli 2003	Not stated	18/69; 26.1%	23/53; 43.4%
Gaafar 2015	Not stated	Not stated	Not stated
Gardner 1998a	46.5%	64/174; 36.8%	53/95; 55.8%	85% women had at least 2 blastocysts
Hatirnaz 2017	52.6%	45/95; 47.4%	43/95; 45.3%
Hreinsson 2004	33%	29/139; 20.9%	24/114; 21.1%	2 morula replaced (one implanted). 60% pregnancy rate when top‐quality blasts transferred
Karaki 2002	33%	37/291 12.7%	37/142; 26.1%	9/80 cancelled due to lack of blastocysts (unselected)
Kaser 2017	Not stated	23/56; 41.1%	26/53; 49.1%
Kaur 2014	Not stated	66/309; 21.4%	102/290; 35.2%
Kolibianakis 2004	50.7%	96/234; 41.0%	94/226; 41.6%
Levi‐Setti 2018	Not stated	25.67%	28.37%
Levitas 2004	43%	4/56; 7.1%	10/24; 4.2%	Day 5‐7 26% cancelled due to lack of blastocysts (poor prognosis)
Levron 2002	34.2%	53/137; 38.7%	20/99; 20.2%	6.5% cancelled due to lack of blastocysts (good prognosis)
Livingstone 2002	Not stated
Motta 1998	Not stated	51/262; 19.5%	36/120; 30.0%	6/58 cycles cancelled D5 no blastocysts
Pantos 2004	44.6%	15.8%	15.8%
Papanikolaou 2005	Not stated	35/170; 20.6%	59/158; 37.3%	4/158 women had only 1 blast transferred due to lack of availability and 1 had it on request
Papanikolaou 2006	Not stated	38/156; 24%	58/149; 38.9%	Number of participants with no embryos available D3: 8 and D5: 11
Rienzi 2002	44.8%	34/96; 35.4%	38/100; 38.0%	Good prognosis
Schillaci 2002	60.3%	23/168; 13.7%	26/110; 23.6%	Unselected population nil cancellations D5
Singh 2017	Not stated	Not stated	Not stated
Ten 2011	Not stated	21/54; 38.9%	26/56; 46.4%	Good prognosis
Van der Auwera 2002	44.7%	31/106; 29.2%	41/90; 45.6%	27% cancellation D5 (unselected population)
Yang 2018	Not stated	80/290; 62.1%	22/306; 72.5%

Table 2. Blastocyst formation and implantation rate (in day 5 to 6 transfers)

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Table 3. Mean number of embryos transferred

Study ID	Day 2/3	Day 5/6
Aziminekoo 2015	2.8 ± 1.1	2.6 ± 0.6
Brugnon 2010	1.0 ± 0	1.0 ± 0
Bungum 2003	2.0 ± NS	2.0 ± NS
Coskun 2000	2.3 ± 0.6	2.2 ± 0.5
Devreker 2000	2.8 ± NS	1.7 ± NS
Elgindy 2011	2.8 ± 0.4	2.0 ± 0.2
Emiliani 2003	2.1 ± 0.4	1.9 ± 0.3
Fernandez‐Shaw 2015	1.5 ± 0.5	1.4 ± 0.5
Fisch 2007	1.0 ± 0	1.0 ± 0
Frattarelli 2003	3.0 ± 0.5	2.0 ± 0.2
Gaafar 2015	NS	NS
Gardner 1998a	3.7 ± 0.1	2.2 ± 0.1
Hatirnaz 2017	1.4 ± 0.6	1.4 ± 0.4
Hreinsson 2004	1.8 ± NS	1.9 ± NS
Karaki 2002	3.5 ± 0.6	2.0 ± 0.1
Kaser 2017	1.0 ± 0	1.0 ± 0
Kaur 2014	2.0 ± 0.7	1.9 ± 0.5
Kolibianakis 2004	1.9 ± 0.1	1.8 ± 0.1
Levi‐Setti 2018	1.9 ± 0.4	1.8 ± 0.6
Levitas 2004	3.4 ± NS	1.9 ± NS
Levron 2002	3.1 ± 0.6	2.3 ± 0.8
Livingstone 2002	2.0 ± NS	1.0 ± NS
Motta 1998	4.6 ± NS	2.3 ± NS
Pantos 2004	4.0 ± 1.5	3.4 ± 1.1
Papanikolaou 2005	2.0 ± 0	2.0 ± 0.5
Papanikolaou 2006	1.0 ± 0	1.0 ± 0
Rienzi 2002	2.0 ± 0	2.0 ± 0
Schillaci 2002	2.8	1.8
Singh 2017	NS	NS
Ten 2011	2.0 ± NS	2.0 ± NS
Van der Auwera 2002	1.9 ± 0.3	1.9 ± 0.2
Yang 2018	1.0 ± 0	1.0 ± 0
NS ‐ not stated

Table 3. Mean number of embryos transferred

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Comparison 1. Blastocyst‐ versus cleavage‐stage transfer: live birth rate following fresh transfer

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Live birth per couple Show forest plot	15	2219	Odds Ratio (M‐H, Fixed, 95% CI)	1.27 [1.06, 1.51]

1.2 Live birth per couple: grouped by number of embryos transferred Show forest plot	15	2677	Odds Ratio (M‐H, Fixed, 95% CI)	1.30 [1.10, 1.53]

1.2.1 More cleavage‐stage than blastocyst embryos transferred	6	483	Odds Ratio (M‐H, Fixed, 95% CI)	1.51 [1.03, 2.22]
1.2.2 Single embryo transfer	2	458	Odds Ratio (M‐H, Fixed, 95% CI)	1.47 [0.98, 2.20]
1.2.3 Equal number of embryos transferred	9	1736	Odds Ratio (M‐H, Fixed, 95% CI)	1.21 [0.99, 1.47]
1.3 Live birth rate per couple: grouped by prognosis Show forest plot	15		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.3.1 good prognostic factors	9	1514	Odds Ratio (M‐H, Fixed, 95% CI)	1.28 [1.04, 1.59]
1.3.2 poor prognostic factors	2	77	Odds Ratio (M‐H, Fixed, 95% CI)	2.05 [0.53, 7.96]
1.3.3 unselected group	4	628	Odds Ratio (M‐H, Fixed, 95% CI)	1.19 [0.86, 1.66]
1.4 Live birth rate: grouped by day of randomisation Show forest plot	15		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.4.1 randomisation at start of cycle	6	1207	Odds Ratio (M‐H, Fixed, 95% CI)	1.08 [0.84, 1.38]
1.4.2 randomised on day of OPU and day 1 after OPU	5	566	Odds Ratio (M‐H, Fixed, 95% CI)	1.16 [0.82, 1.65]
1.4.3 randomised day 2 to 3 post‐OPU	2	364	Odds Ratio (M‐H, Fixed, 95% CI)	2.17 [1.42, 3.33]
1.4.4 day of randomisation unstated	2	82	Odds Ratio (M‐H, Fixed, 95% CI)	1.71 [0.67, 4.39]

Comparison 1. Blastocyst‐ versus cleavage‐stage transfer: live birth rate following fresh transfer

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Comparison 2. Blastocyst‐ versus cleavage‐stage transfer: cumulative pregnancy rate following fresh and frozen transfer

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Cumulative pregnancy rate from fresh and frozen transfers Show forest plot	5	632	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.64, 1.22]

2.2 Cumulative pregnancy rate per couple: grouped by number of embryos transferred Show forest plot	5	739	Odds Ratio (M‐H, Fixed, 95% CI)	0.88 [0.65, 1.18]

2.2.1 single embryo transfer	1	107	Odds Ratio (M‐H, Fixed, 95% CI)	0.84 [0.39, 1.79]
2.2.2 equal number of embryos transferred	5	632	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.64, 1.22]
2.3 Cumulative pregnancy rate per couple: grouped by prognosis Show forest plot	5	632	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.64, 1.22]

2.3.1 good prognostic factors	2	205	Odds Ratio (M‐H, Fixed, 95% CI)	0.54 [0.30, 0.98]
2.3.2 unselected group	3	427	Odds Ratio (M‐H, Fixed, 95% CI)	1.10 [0.74, 1.61]
2.4 Cumulative pregnancy rate: grouped by day of randomisation Show forest plot	5	632	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.64, 1.22]

2.4.1 randomisation at start of cycle	3	414	Odds Ratio (M‐H, Fixed, 95% CI)	0.81 [0.54, 1.20]
2.4.2 randomised on day of OPU and day 1 after OPU	2	218	Odds Ratio (M‐H, Fixed, 95% CI)	1.06 [0.61, 1.83]
2.5 Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing Show forest plot	5		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.5.1 slow freezing	4	512	Odds Ratio (M‐H, Fixed, 95% CI)	0.69 [0.48, 0.99]
2.5.2 vitrification	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	2.44 [1.17, 5.12]

Comparison 2. Blastocyst‐ versus cleavage‐stage transfer: cumulative pregnancy rate following fresh and frozen transfer

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Comparison 3. Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Clinical pregnancy rate per couple Show forest plot	32	5821	Odds Ratio (M‐H, Fixed, 95% CI)	1.25 [1.12, 1.39]

3.2 Clinical pregnancy rate per couple: grouped by number of embryos transferred Show forest plot	32	7062	Odds Ratio (M‐H, Fixed, 95% CI)	1.26 [1.14, 1.38]

3.2.1 equal number of embryo transfers	20	4434	Odds Ratio (M‐H, Fixed, 95% CI)	1.31 [1.16, 1.48]
3.2.2 more cleavage stage than blastocyst embryos transferred	12	1387	Odds Ratio (M‐H, Fixed, 95% CI)	1.07 [0.86, 1.33]
3.2.3 single embryo transfer	5	1241	Odds Ratio (M‐H, Fixed, 95% CI)	1.31 [1.04, 1.65]
3.3 Clinical pregnancy rate per couple: grouped by prognosis Show forest plot	32	5821	Odds Ratio (M‐H, Fixed, 95% CI)	1.25 [1.12, 1.39]

3.3.1 good prognostic factors	19	3645	Odds Ratio (M‐H, Fixed, 95% CI)	1.25 [1.09, 1.43]
3.3.2 poor prognostic factors	3	195	Odds Ratio (M‐H, Fixed, 95% CI)	1.62 [0.84, 3.10]
3.3.3 unselected group	10	1981	Odds Ratio (M‐H, Fixed, 95% CI)	1.22 [1.01, 1.46]
3.4 Clinical pregnancy rate per couple: grouped by day of randomisation Show forest plot	32	5821	Odds Ratio (M‐H, Fixed, 95% CI)	1.25 [1.12, 1.39]

3.4.1 randomised start of cycle	8	1759	Odds Ratio (M‐H, Fixed, 95% CI)	1.12 [0.92, 1.37]
3.4.2 randomised on day of OPU or day 1	13	2094	Odds Ratio (M‐H, Fixed, 95% CI)	1.19 [1.00, 1.42]
3.4.3 randomised on day 2 to 3	6	1275	Odds Ratio (M‐H, Fixed, 95% CI)	1.50 [1.19, 1.88]
3.4.4 day of randomisation unstated	5	693	Odds Ratio (M‐H, Fixed, 95% CI)	1.33 [0.98, 1.80]
3.5 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage Show forest plot	2	709	Odds Ratio (M‐H, Fixed, 95% CI)	1.41 [1.04, 1.90]

3.6 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus TLS (with algorithm) blastocyst stage Show forest plot	1	110	Odds Ratio (M‐H, Fixed, 95% CI)	0.91 [0.43, 1.96]

Comparison 3. Blastocyst‐ versus cleavage‐stage transfer: clinical pregnancy following fresh transfer

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Comparison 4. Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Multiple pregnancy rate per couple Show forest plot	22	4208	Odds Ratio (M‐H, Fixed, 95% CI)	1.12 [0.90, 1.38]

4.2 Multiple pregnancy rate per couple: grouped by number of embryos transferred Show forest plot	22	5159	Odds Ratio (M‐H, Fixed, 95% CI)	1.12 [0.91, 1.38]

4.2.1 equal number of embryos transferred	14	3399	Odds Ratio (M‐H, Fixed, 95% CI)	1.29 [1.01, 1.65]
4.2.2 more cleavage stage than blastocyst embryos transferred	8	809	Odds Ratio (M‐H, Fixed, 95% CI)	0.75 [0.49, 1.13]
4.2.3 single embryo transfer	2	951	Odds Ratio (M‐H, Fixed, 95% CI)	1.22 [0.51, 2.91]
4.3 Multiple pregnancy rate per couple: grouped by prognosis Show forest plot	22	4208	Odds Ratio (M‐H, Fixed, 95% CI)	1.12 [0.90, 1.38]

4.3.1 good prognostic factors	15	2904	Odds Ratio (M‐H, Fixed, 95% CI)	1.14 [0.89, 1.46]
4.3.2 poor prognostic factors	1	54	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.14, 5.81]
4.3.3 unselected	6	1250	Odds Ratio (M‐H, Fixed, 95% CI)	1.07 [0.71, 1.59]
4.4 Multiple pregnancy rate per couple: grouped by day of randomisation Show forest plot	22	4208	Odds Ratio (M‐H, Fixed, 95% CI)	1.12 [0.90, 1.38]

4.4.1 randomised start of cycle	7	1704	Odds Ratio (M‐H, Fixed, 95% CI)	1.02 [0.71, 1.46]
4.4.2 randomised on day of OPU or day 1	9	1647	Odds Ratio (M‐H, Fixed, 95% CI)	1.05 [0.73, 1.52]
4.4.3 randomised on day 2 to 3	4	682	Odds Ratio (M‐H, Fixed, 95% CI)	1.71 [1.14, 2.56]
4.4.4 day of randomisation unstated	2	175	Odds Ratio (M‐H, Fixed, 95% CI)	0.21 [0.06, 0.70]
4.5 High‐order pregnancies (more than 2 gestational sacs) per couple Show forest plot	13	2335	Odds Ratio (M‐H, Fixed, 95% CI)	0.45 [0.18, 1.15]

4.6 Multiple pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage Show forest plot	1	600	Odds Ratio (M‐H, Fixed, 95% CI)	1.59 [0.61, 4.17]

Comparison 4. Blastocyst‐ versus cleavage‐stage transfer: multiple pregnancy following fresh transfer

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Comparison 5. Blastocyst‐ versus cleavage‐stage transfer: miscarriage rate following fresh transfer

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Miscarriage rate per couple Show forest plot	21	4106	Odds Ratio (M‐H, Fixed, 95% CI)	1.24 [0.98, 1.57]

Comparison 5. Blastocyst‐ versus cleavage‐stage transfer: miscarriage rate following fresh transfer

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Comparison 6. Blastocyst‐ versus cleavage‐stage transfer: embryo freezing rate per couple

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Embryo freezing per couple Show forest plot	14	2292	Odds Ratio (M‐H, Fixed, 95% CI)	0.48 [0.40, 0.57]

Comparison 6. Blastocyst‐ versus cleavage‐stage transfer: embryo freezing rate per couple

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Comparison 7. Blastocyst‐ versus cleavage‐stage transfer: failure rate to transfer embryos (per couple)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
7.1 Failure to transfer any embryos (per couple) Show forest plot	17	2577	Odds Ratio (M‐H, Fixed, 95% CI)	2.50 [1.76, 3.55]

Comparison 7. Blastocyst‐ versus cleavage‐stage transfer: failure rate to transfer embryos (per couple)

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Risk of bias for analysis 1.1 Live birth per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Risk of bias for analysis 1.1 Live birth per couple

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Risk of bias for analysis 1.2 Live birth per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.2.1 More cleavage‐stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Subgroup 1.2.2 Single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 1.2.3 Equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Risk of bias for analysis 1.2 Live birth per couple: grouped by number of embryos transferred

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Risk of bias for analysis 1.3 Live birth rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.3.2 poor prognostic factors
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 1.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Risk of bias for analysis 1.3 Live birth rate per couple: grouped by prognosis

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Risk of bias for analysis 1.4 Live birth rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 1.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalised before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 1.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 1.4.3 randomised day 2 to 3 post‐OPU
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 1.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.

Risk of bias for analysis 1.4 Live birth rate: grouped by day of randomisation

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Risk of bias for analysis 2.1 Cumulative pregnancy rate from fresh and frozen transfers

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Risk of bias for analysis 2.1 Cumulative pregnancy rate from fresh and frozen transfers

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Risk of bias for analysis 2.2 Cumulative pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.2.1 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Subgroup 2.2.2 equal number of embryos transferred
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	information. Only proportions were reproted

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Risk of bias for analysis 2.2 Cumulative pregnancy rate per couple: grouped by number of embryos transferred

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Risk of bias for analysis 2.3 Cumulative pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Subgroup 2.3.2 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Risk of bias for analysis 2.3 Cumulative pregnancy rate per couple: grouped by prognosis

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Risk of bias for analysis 2.4 Cumulative pregnancy rate: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.4.1 randomisation at start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methods are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.4.2 randomised on day of OPU and day 1 after OPU
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.

Risk of bias for analysis 2.4 Cumulative pregnancy rate: grouped by day of randomisation

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Risk of bias for analysis 2.5 Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 2.5.1 slow freezing
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 2.5.2 vitrification
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.

Risk of bias for analysis 2.5 Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing

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Risk of bias for analysis 3.1 Clinical pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is some risk of bias due to the randomisation process, to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Risk of bias for analysis 3.1 Clinical pregnancy rate per couple

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Risk of bias for analysis 3.2 Clinical pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.2.1 equal number of embryo transfers
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.2.2 more cleavage stage than blastocyst embryos transferred
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 3.2.3 single embryo transfer
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Risk of bias for analysis 3.2 Clinical pregnancy rate per couple: grouped by number of embryos transferred

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Risk of bias for analysis 3.3 Clinical pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.3.1 good prognostic factors
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.3.2 poor prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 3.3.3 unselected group
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Risk of bias for analysis 3.3 Clinical pregnancy rate per couple: grouped by prognosis

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Risk of bias for analysis 3.4 Clinical pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 3.4.1 randomised start of cycle
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	High risk due to deviation from the intended interventions and bias due to missing outcome data
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 3.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All women randomised were analysed

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fisch 2007

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Although the number of missing outcomes is high, there is no evidence of bias about it

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to the randomisation process, due to deviations from the intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignment

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Schillaci 2002

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 3.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Singh 2017

	No information about the allocation sequence concealment and no information about the baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	It is not possible to know if there were missing outcome data.

	Method of measuring the outcome was not informed, but it was probably not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is a high risk of bias due to deviations from the intended interventions and missing outcomes data. And some concerns of risk of bias due to randomisation process and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Subgroup 3.4.4 day of randomisation unstated
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concerns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	Clinical pregnancy with cardiac pulsation four weeks after ET. PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.

Risk of bias for analysis 3.4 Clinical pregnancy rate per couple: grouped by day of randomisation

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Risk of bias for analysis 3.5 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Risk of bias for analysis 3.5 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

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Risk of bias for analysis 3.6 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus TLS (with algorithm) blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Kaser 2017

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	The observed number of events is much greater than the number of participants with missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote:"NCT02218255"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Risk of bias for analysis 3.6 Clinical pregnancy rate per couple: TLS (with algorithm) cleavage stage versus TLS (with algorithm) blastocyst stage

Ir a la tabla de la revisión

Risk of bias for analysis 4.1 Multiple pregnancy rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to the randomisation process and deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Risk of bias for analysis 4.1 Multiple pregnancy rate per couple

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Risk of bias for analysis 4.2 Multiple pregnancy rate per couple: grouped by number of embryos transferred

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.2.1 equal number of embryos transferred
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.2.2 more cleavage stage than blastocyst embryos transferred
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Subgroup 4.2.3 single embryo transfer
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Risk of bias for analysis 4.2 Multiple pregnancy rate per couple: grouped by number of embryos transferred

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Risk of bias for analysis 4.3 Multiple pregnancy rate per couple: grouped by prognosis

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.3.1 good prognostic factors
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.3.2 poor prognostic factors
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Subgroup 4.3.3 unselected
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Risk of bias for analysis 4.3 Multiple pregnancy rate per couple: grouped by prognosis

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Risk of bias for analysis 4.4 Multiple pregnancy rate per couple: grouped by day of randomisation

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Subgroup 4.4.1 randomised start of cycle
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Subgroup 4.4.2 randomised on day of OPU or day 1
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.
Subgroup 4.4.3 randomised on day 2 to 3
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All ranomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Subgroup 4.4.4 day of randomisation unstated
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.

Risk of bias for analysis 4.4 Multiple pregnancy rate per couple: grouped by day of randomisation

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Risk of bias for analysis 4.5 High‐order pregnancies (more than 2 gestational sacs) per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to randomisation process, deviations from the intended interventions, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Risk of bias for analysis 4.5 High‐order pregnancies (more than 2 gestational sacs) per couple

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Risk of bias for analysis 4.6 Multiple pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Risk of bias for analysis 4.6 Multiple pregnancy rate per couple: TLS (with algorithm) cleavage stage versus conventional blastocyst stage

Ir a la tabla de la revisión

Risk of bias for analysis 5.1 Miscarriage rate per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to randomization process and selection of the reported result
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Elgindy 2011

	The number of embryos per transfer was significantly higher in group than the other group

	This open‐label, prospective, randomized, controlled trial. No information about a deviation from the intended protocols

	All randomised women were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process, deviations from intended interventions and selection of reported results.
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Gaafar 2015

	Quote "Randomization was done by computer permuted blocks size of 4, allocation by closed envelops, parallel technique" No mention about opaque envelopes

	Not evidence of potential of concearns generating a substantial impact

	A large proportion of missing outcomes: 326 were eligible. 126 cases had day 2/3 transfer and 126 had blastocyst transfer.

	PACTR201308000581376 Quote "Masking Care giver/Provider,Outcome assessors,Participants"

	There is only a difference in outcome reporting regarding multiple pregnancies

	High bias due to missing outcome data and some concerns due to deviations from intended interventions and bias in selection of the reported result
Hatirnaz 2017

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	95 out of 100 women of each arm had data to analyze

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kaur 2014

	No information if the allocation sequence was random and/or concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, and selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levi‐Setti 2018

	Allocation sequence was not concealed but no baseline clinical and statistical differences between groups were found in a table that described more than 15 different variables.

	Participants and embryologists were aware of their assigned intervention. No deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	No lost to follow up

	Method of measuring the outcome was not informed. However, given the nature of the outcome and the methods to measure it, it was probably not different between groups and, as it is an objective outcome, it is unlikely to be influenced by the knowledge of the assigned intervention.

	Data that produced this result was analysed in accordance with a pre‐specified analysis plan that was finalized before unblinded outcome data were available for analysis

	There is some concerns of risk of bias due to randomisation process.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Livingstone 2002

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.
Yang 2018

	Allocation sequence was random and concealed

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the number of randomised women per arm and it is not possible to know how the analysis was performed.

	The observed number of events is much greater than the number of participants with missing outcome data, but it is probably not related with the true value

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	Quote" ChiCTR‐ICR‐15006600"

	There are some concerns of risk of bias due to deviations from the intended interventions.

Risk of bias for analysis 5.1 Miscarriage rate per couple

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Risk of bias for analysis 6.1 Embryo freezing per couple

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Brugnon 2010

	Sequence generated but there was no information about concealment. No table of patients' baseline characteristics reported

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No information about the deviations or the analysis

	No information. Only proportions were reported

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk due to deviation from the intended interventions
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Fernandez‐Shaw 2015

	No statement about allocation concealment.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, in both groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Pantos 2004

	No information about the allocation sequence random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	There is no information about the method of measuring the outcome, but it is probable that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Ten 2011

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. And no information about the analysis that was performed.

	No information about neither the absolute number of events nor the missing outcome data.

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and missing outcomes, and some concerns of risk of bias due to randomisation process and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Risk of bias for analysis 6.1 Embryo freezing per couple

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Risk of bias for analysis 7.1 Failure to transfer any embryos (per couple)

Bias
Study	Randomisation process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported results	Overall
Gardner 1998a

	Concealment was not reported, there was a difference in Previous no. of cycles

	No effort for blindness is described. There was a difference No. of embryos transferred and proportion of embryo freezing that likely have affected the outcome

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	ClinicalTrials.gov Identifier: NCT03764865

	High risk of bias due to deviations from intended intervention
Aziminekoo 2015

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All 118 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Bungum 2003

	There was not a complete explanation about concealment and there are some concerns about baseline differences

	No effort for blindness is described. All 118 randomised women were analysed.

	All 118 randomised women were analysed.

	Method of measuring the outcome was probably appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results
Coskun 2000

	Randomisation process apparently has no problems. Patients were randomized to receive embryo transfer either at day 3 or day 5. Quote " An equal number of ‘day 3' or ‘day 5' labels placed in sealed envelopes in a block of 14 was kept in a box and an envelope was drawn by the embryologist as soon as a patient qualified for the study. The label was attached with adhesive to the patients’ data collection sheet."

	Participants and carers and people delivering the intervention were probably aware of their assigned intervention.

	All 201 randomised women were available.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	Some concerns due to deviation from intended interventions and selection of reported outcomes
Devreker 2000

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidencesuggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions and there are some concerns of risk of bias due to the selection of reported results.
Emiliani 2003

	Concealment was not stated. Only minor differences in age

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention.

	All women randomised were analysed

	Not reported but inappropriate methotds are unlikely. It is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention

	No protocol registration was found.

	There some concerns of risk of bias due to the randomisation process and selection of reported results.
Frattarelli 2003

	Randomization was accomplished using a computer‐generated randomization table. The sequences of randomization were concealed until intervention was assigned. The groups were balanced. Concealment method was not described.

	Those patients undergoing a day 5 ET had a significantly higher implantation rate than those undergoing a day 3, these deviations likely have affected the outcome

	All women randomised were analysed

	Method of measuring the outcome was probably appropriate, no different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	High risk of bias due to deviations from the intended protocol and some concerns due to bias in selection of the reported result.
Hreinsson 2004

	Allocation sequence was random and concealed. Quote:"Sealed envelopes were used for randomisation of the patients for each group". Groups were balanced.

	No effort for blindness is described. Considering the nature of the intervention, it is very unlikely that participants and carers and people delivering the intervention were not aware of their assigned intervention. No differences in embryos per transfer bat there was for cycles with embryo freezing. All women randomised were analyses by assignement

	All women randomised were analysed

	Knowledge of the assigned intervention is unlikely to influence this objective outcome assessment.

	No protocol registration was found.

	Some concerns of risk of bias due to selection of reported results.
Karaki 2002

	No information if the allocation sequence was random, but it was concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. All randomised women were analysed.

	No missing outcome data.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Kolibianakis 2004

	Allocation sequence was random but it was not concealed. No baseline differences between groups were found.

	Participants, carers and people delivering the intervention were aware of their assigned intervention. No information about a deviation from the intended protocols. No information if there was a substantial impact of the failure to analyse participants in the group to which they were randomized.

	All randomised women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are high of risk of bias due to deviations from the intended interventions and randomisation process, and some concerns of risk of bias due to selection of reported results.
Levitas 2004

	Allocation sequence was random and concealed and no baseline differences were found between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was probably a deviation from the intended protocols. Analysis was done by ITT

	Although there are missing outcome data, the missingness in the outcome probably does not depend on its true value.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to devitations of the protocol and some concerns of risk of bias due to selection of reported results.
Levron 2002

	No information if the allocation sequence was random and concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. Analysis was performed by intention‐to‐treat.

	Only 3 out of 46 in the blastocyst group did not have embryo transfer

	Method of measuring the outcome was not stated, but it is not probable that it was measured different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Motta 1998

	No information available to know if the allocation sequence was random or the allocation sequence was concealed. And no information about baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There was evidence suggesting deviation from the intended protocols. All randomised women were analysed.

	No lost to follow up

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to the randomisation process, deviations from the intended interventions and there are some concerns of risk of bias due to the randomisation process and selection of reported results.
Papanikolaou 2005

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed.

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process, deviations from the intended interventions and selection of reported results.
Papanikolaou 2006

	There was not enough information to evaluate the method of allocation sequence concealment.

	Participants were probably aware of their assigned intervention. No deviation from the intended protocols. All randomised women were analysed.

	All the randomized women were analysed

	Method of measuring the outcome was appropriate, was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to randomisation process and selection of reported results.
Rienzi 2002

	No information about the allocation sequence concealed but no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. No information about a deviation from the intended protocols and no information about the total number of randomised women.

	No information about neither the total number of randomized women nor the missing outcome data.

	Method of measuring the outcome was appropriate, it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There is high risk of bias due to deviations from the intended interventions, and there are some concerns of risk of bias due to randomisation process, missing outcomes and selection of reported results.
Van der Auwera 2002

	No information available to know if the allocation sequence was random. However, allocation sequence was concealed and no baseline differences between groups.

	Participants, carers and people delivering the intervention were probably aware of their assigned intervention. There were only few with deviation from the intended protocols, and no imbalance was found. All randomised women were analysed.

	Quote: “Three patients were excluded for analysis from group 1 because they wanted an elective blastocyst culture while four patients were excluded from group 2 because they wanted an elective day 2 transfer.”

	Method of measuring the outcome was not described. However, it is unlikely that it was not different between groups and it is an objective outcome that is unlikely to be influenced by the knowledge of the assigned intervention.

	No protocol registration was found.

	There are some concerns of risk of bias due to deviations from the intended interventions and selection of reported results.

Risk of bias for analysis 7.1 Failure to transfer any embryos (per couple)

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Referencias

Referencias de los estudios incluidos en esta revisión

Aziminekoo 2015 {published data only}

Brugnon 2010 {published data only}

Bungum 2003 {published data only}

Coskun 2000 {published data only}

Devreker 2000 {published data only}

Elgindy 2011 {published data only}

Emiliani 2003 {published data only}

Fernandez‐Shaw 2015 {published data only}

Fisch 2007 {published data only}

Frattarelli 2003 {published data only}

Gaafar 2015 {published data only}

Gardner 1998a {published data only}

Hatirnaz 2017 {published data only}

Hreinsson 2004 {published data only}

Karaki 2002 {published data only}

Kaser 2017 {published data only}

Kaur 2014 {published data only}

Kolibianakis 2004 {published data only}

Levi‐Setti 2018 {published data only}

Levitas 2004 {published data only}

Levron 2002 {published data only}

Livingstone 2002 {published and unpublished data}

Motta 1998 {published data only}

Pantos 2004 {published data only}

Papanikolaou 2005 {published data only}

Papanikolaou 2006 {published data only}

Rienzi 2002 {published data only}

Schillaci 2002 {published data only}

Singh 2017 {published data only}

Ten 2011 {published data only}

Van der Auwera 2002 {published data only}

Yang 2018 {published data only}

Referencias de los estudios excluidos de esta revisión

Bungum 2002 {published data only}

Cornelisse 2018 {published data only}

Green 2016 {published data only}

Guerin 1991 {published data only}

Holden 2017 {published data only}

Levron 2001 {published data only}

Loup 2009 {published data only}

Menezo 1992 {published data only}

Utsonomiya 2004 {published data only}

Zech 2007 {published data only}

Referencias de los estudios en espera de evaluación

Clua Obrado 2020 {published data only}

Referencias de los estudios en curso

ChiCTR‐ICR‐15006184 {published data only}

Cornelisse 2021 {published data only}

ISRCTN48090543 {published data only}

NCT01107002 {published data only}

NCT02639000 {published data only}

NCT04210414 {published data only}

Neuhausser 2020 {published data only}

PACTR201402000773124 {published data only}

PACTR201709002592834 {published data only}

Referencias adicionales

Alviggi 2018

Armstrong 2019

Baart 2006

Begg 1996

Behr 2000

Borg 2000

Braude 1998

Busnelli 2019

Cohen 1990

Cornelisse 2018

Croxatto 1972

De Felici 1982

De Placido 2002

Edgar 2012

Edwards 1995

Fanchin 2001

Gardner 1996

Gardner 1998b

Gardner 2003

Gardner 2004