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Cochrane Database of Systematic Reviews

Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology

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Información

DOI:
https://doi.org/10.1002/14651858.CD002118.pub5Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 30 junio 2016see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:
  1. Grupo Cochrane de Ginecología y fertilidad

Copyright:
  1. Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Autores

  • Demián Glujovsky

    Correspondencia a: Reproductive Medicine, CEGYR (Centro de Estudios en Genética y Reproducción), Buenos Aires, Argentina

    [email protected]

  • Cindy Farquhar

    Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand

  • Andrea Marta Quinteiro Retamar

    Eggs donation program, Genetics unit, CEGYR (Centro de Estudios en Ginecologia y Reproducción), Buenos Aires, Argentina

  • Cristian Roberto Alvarez Sedo

    Laboratory of Reproductive Biology and Genetics, CEGYR, Buenos Aires, Argentina

  • Deborah Blake

    Repromed Fertility Specialists, Auckland, New Zealand

Contributions of authors

Debbie Blake: for the initial review and updates to 2005, took the lead in writing the protocol and review, performed initial searches of databases for trials, involved in selecting trials for inclusion, performed independent data extraction and quality assessment of the included trials, and was responsible for statistical analysis and interpretation of the data. Also contributed to the final analysis and text of the 2012 and 2016 updates.

Cindy Farquhar: for the 2005 update, added in the new studies, redesigned the table of comparisons and rewrote the results section, as well as edited the review. Also contributed to the 2007, 2012, and 2016 updates with assistance in extraction and interpretation of the data and writing in all sections.

Demián Glujovsky: for the 2012 and 2016 updates, took the lead in writing the update of the review, performed new searches of databases for trials, involved in selecting trials for inclusion, performed independent data extraction and quality assessment of the included trials, and was responsible for statistical analysis and interpretation of the data in the update.

Andrea Quinteiro Retamar: for the 2016 update, involved in selecting trials for inclusion, and performed independent data extraction and quality assessment of the included trials.

Cristian Alvarez Sedo: for the final analysis and text of the 2016 update.

Sources of support

Internal sources

  • Cindy Farquhar, New Zealand.

    University of Auckland

External sources

  • None, Other.

Declarations of interest

Cindy Farquhar is a director/shareholder of a fertility/gynaecology clinic and undertakes private practice within those premises.

Demián Glujovsky is part of medical staff of a fertility clinic and undertakes private practice within those premises.

Andrea Quinteiro Retamar is the egg donor coordinator of a fertility clinic and undertakes private practice within those premises.

No other authors have any conflict of interest to declare.

Acknowledgements

The authors acknowledge the helpful comments of those who refereed previous versions of this review, in particular Mr Andy Vail and Dr Gayle Jones. Thanks to Dr Plachot, Dr Huisman, Dr Utsunomiya, Dr Hreinsson, Dr Rienzi, Dr Levron, Dr Levitas, Dr Bungum, Dr Papanikolaou, Dr Karaki, Dr Frattarelli, Dr Brugnon, Dr Vanderzwalmen and Dr Fernández‐Shaw for supplying additional information. Thanks to the librarian Daniel Comandé. Finally, special thanks to the highly supportive team at the Cochrane office in Auckland.

Dr Neil Johnson was a review author for the previous version of this review and made a significant contribution to the interpretation of results and performed some data extraction. David Olive, for the initial review, commented on drafts of the protocol and review. Michelle Proctor, for the initial review, was involved in selecting trials for inclusion, performed independent data extraction and quality assessment of the included trials, contributed to the discussion and interpretation of results. Quirine Lamberts, for the 2005 update, checked the data and study information extracted. Ariel Bardach, for the 2012 update, was involved in selecting trials for inclusion, performed independent data extraction, and quality assessment of the included trials.

Version history

Published

Title

Stage

Authors

Version

2022 May 19

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

Review

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

https://doi.org/10.1002/14651858.CD002118.pub6

2016 Jun 30

Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology

Review

Demián Glujovsky, Cindy Farquhar, Andrea Marta Quinteiro Retamar, Cristian Roberto Alvarez Sedo, Deborah Blake

https://doi.org/10.1002/14651858.CD002118.pub5

2012 Jul 11

Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology

Review

Demián Glujovsky, Debbie Blake, Ariel Bardach, Cindy Farquhar

https://doi.org/10.1002/14651858.CD002118.pub4

2007 Oct 17

Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology

Review

Debbie Blake, Cindy Farquhar, Neil Johnson, Michelle Proctor

https://doi.org/10.1002/14651858.CD002118.pub3

2005 Oct 19

Cleavage stage versus blastocyst stage embryo transfer in assisted conception

Review

Debbie A Blake, Michelle Proctor, Neil Johnson, David Olive, Cindy M Farquhar, Quirine Lamberts

https://doi.org/10.1002/14651858.CD002118.pub2

2002 Apr 22

Cleavage stage versus blastocyst stage embryo transfer in assisted conception

Review

Debbie DA Blake, Michelle Proctor, Neil Johnson, David Olive

https://doi.org/10.1002/14651858.CD002118

Differences between protocol and review

  • We only included RCTs and excluded quasi RCTs (2007 update)

  • We excluded couples or women where frozen‐thawed cycle results were shown, but no data were available from the fresh cycle (2016 update)

  • Addition of cumulative pregnancy rate to the primary outcomes (previously a secondary outcome) (2007 update)

  • Subgroup and sensitivity analyses restricted to specific clinical outcomes: live birth, cumulative pregnancy, clinical pregnancy, and multiple pregnancy (2007 update)

  • Addition of a posthoc subgroup analysis according to freezing technique, to investigate statistical heterogeneity for the outcome cumulative pregnancy rate (2016 update)

  • Objectives shortened to current wording (2012 update)

Notes

Conflict of interest added.

Keywords

MeSH

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Study flow diagram: Results of search from review inception to 2016
Figuras y tablas -
Figure 1

Study flow diagram: Results of search from review inception to 2016

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Forest plot of comparison: 1 Blastocyst versus cleavage stage transfer: Live birth rate, outcome: 1.1 Live birth per couple.
Figuras y tablas -
Figure 4

Forest plot of comparison: 1 Blastocyst versus cleavage stage transfer: Live birth rate, outcome: 1.1 Live birth per couple.

Forest plot of comparison: 2 Blastocyst versus cleavage stage transfer: Cumulative pregnancy rate following fresh and frozen transfer, outcome: 2.5 Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing.
Figuras y tablas -
Figure 5

Forest plot of comparison: 2 Blastocyst versus cleavage stage transfer: Cumulative pregnancy rate following fresh and frozen transfer, outcome: 2.5 Cumulative pregnancy rate from fresh and frozen transfers: grouped by vitrification or slow freezing.

Forest plot of comparison: 2 Blastocyst versus cleavage stage transfer: Clinical pregnancy rate, outcome: 2.1 clinical pregnancy rate per couple.
Figuras y tablas -
Figure 6

Forest plot of comparison: 2 Blastocyst versus cleavage stage transfer: Clinical pregnancy rate, outcome: 2.1 clinical pregnancy rate per couple.

Funnel plot of comparison: 1 Blastocyst versus cleavage stage transfer: Live birth rate, outcome: 1.1 Live birth per couple.
Figuras y tablas -
Figure 7

Funnel plot of comparison: 1 Blastocyst versus cleavage stage transfer: Live birth rate, outcome: 1.1 Live birth per couple.

Funnel plot of comparison: 2 Blastocyst versus cleavage stage transfer: Clinical pregnancy rate, outcome: 2.1 clinical pregnancy rate per couple.
Figuras y tablas -
Figure 8

Funnel plot of comparison: 2 Blastocyst versus cleavage stage transfer: Clinical pregnancy rate, outcome: 2.1 clinical pregnancy rate per couple.

Comparison 1 Blastocyst versus cleavage stage transfer: Live birth rate following fresh transfer, Outcome 1 Live birth per couple.
Figuras y tablas -
Analysis 1.1

Comparison 1 Blastocyst versus cleavage stage transfer: Live birth rate following fresh transfer, Outcome 1 Live birth per couple.

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.
Figuras y tablas -
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.

Comparison 1 Blastocyst versus cleavage stage transfer: Live birth rate following fresh transfer, Outcome 3 Live birth rate per couple: grouped by prognosis.
Figuras y tablas -
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.

Comparison 1 Blastocyst versus cleavage stage transfer: Live birth rate following fresh transfer, Outcome 4 Live birth rate: grouped by day of randomisation.
Figuras y tablas -
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.

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.
Figuras y tablas -
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.

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.
Figuras y tablas -
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.

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.
Figuras y tablas -
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.

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.
Figuras y tablas -
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.

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.
Figuras y tablas -
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.

Comparison 3 Blastocyst versus cleavage stage transfer: Clinical pregnancy following fresh transfer, Outcome 1 Clinical pregnancy rate per couple.
Figuras y tablas -
Analysis 3.1

Comparison 3 Blastocyst versus cleavage stage transfer: Clinical pregnancy following fresh transfer, Outcome 1 Clinical pregnancy rate per couple.

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.
Figuras y tablas -
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.

Comparison 3 Blastocyst versus cleavage stage transfer: Clinical pregnancy following fresh transfer, Outcome 3 Clinical pregnancy rate per couple: grouped by prognosis.
Figuras y tablas -
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.

Comparison 3 Blastocyst versus cleavage stage transfer: Clinical pregnancy following fresh transfer, Outcome 4 Clinical pregnancy rate per couple: grouped by day of randomisation.
Figuras y tablas -
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.

Comparison 4 Blastocyst versus cleavage stage transfer: Multiple pregnancy following fresh transfer, Outcome 1 Multiple pregnancy rate per couple.
Figuras y tablas -
Analysis 4.1

Comparison 4 Blastocyst versus cleavage stage transfer: Multiple pregnancy following fresh transfer, Outcome 1 Multiple pregnancy rate per couple.

Comparison 4 Blastocyst versus cleavage stage transfer: Multiple pregnancy following fresh transfer, Outcome 2 Multiple pregnancy rate per couple: grouped by number of embryo transfer.
Figuras y tablas -
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 embryo transfer.

Comparison 4 Blastocyst versus cleavage stage transfer: Multiple pregnancy following fresh transfer, Outcome 3 Multiple pregnancy rate per couple: grouped by prognosis.
Figuras y tablas -
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.

Comparison 4 Blastocyst versus cleavage stage transfer: Multiple pregnancy following fresh transfer, Outcome 4 Multiple pregnancy rate per couple: grouped by day of randomisation.
Figuras y tablas -
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.

Comparison 4 Blastocyst versus cleavage stage transfer: Multiple pregnancy following fresh transfer, Outcome 5 High order pregnancies (more than 2 gestational sacs) per couple.
Figuras y tablas -
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.

Comparison 5 Blastocyst versus cleavage stage transfer: Miscarriage rate following fresh transfer, Outcome 1 Miscarriage rate per couple.
Figuras y tablas -
Analysis 5.1

Comparison 5 Blastocyst versus cleavage stage transfer: Miscarriage rate following fresh transfer, Outcome 1 Miscarriage rate per couple.

Comparison 6 Blastocyst versus cleavage stage transfer: Embryo freezing rate per couple, Outcome 1 Embryo freezing per couple.
Figuras y tablas -
Analysis 6.1

Comparison 6 Blastocyst versus cleavage stage transfer: Embryo freezing rate per couple, Outcome 1 Embryo freezing per couple.

Comparison 7 Blastocyst versus cleavage stage transfer: Failure rate to transfer embryos (per couple), Outcome 1 Failure to transfer any embryos (per couple).
Figuras y tablas -
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).

Summary of findings for the main comparison. Blastocyst stage versus cleavage stage embryo transfer for assisted reproductive technology

Blastocyst stage versus cleavage stage embryo transfer for assisted reproductive technology

Population: Couples with subfertility
Settings: Assisted reproductive technology
Intervention: Blastocyst stage embryo transfer
Comparison: Cleavage stage embryo transfer

Outcomes per couple

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No. of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Cleavage stage embryo transfer

Blastocyst stage

Live birth rate

286 per 1000

372 per 1000

(324 to 421)

OR 1.48
(1.20 to 1.82)

1630

(13 studies)

⊕⊕⊝⊝
low1

Cumulative pregnancy rate

481 per 1000

452 per 1000

(372 to 530)

OR 0.89

(0.64 to 1.22)

632

(5 studies)

⊕⊝⊝⊝
very low2,3,4

I2 = 71%, attributable to the use of vitrification in one study and slow freezing in the other four

Clinical pregnancy rate

362 per 1000

425 per 1000
(393 to 455)

OR 1.30
(1.14 to 1.47)

4031
(27 studies)

⊕⊕⊝⊝
moderate2

Multiple pregnancy rate

122 per 1000

127 per 1000
(103 to 156)

OR 1.05
(0.83 to 1.33)

3019
(19 studies)

⊕⊕⊝⊝
low1

Miscarriage rate

68 per 1000

78 per 1000
(68 to 119)

OR 1.15
(0.88 to 1.50)

2917
(18 studies)

⊕⊕⊝⊝
low2,3

Embryo freezing rate

594 per 1000

412 per 1000

(369 to 455)

OR 0.48

(0.40 to 0.57)

2292

(14 studies)

⊕⊕⊝⊝
low2,4

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)

⊕⊕⊕⊝
moderate2

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.

1Downgraded two levels for very serious risk of bias: several studies did not describe acceptable methods of sequence generation and/or allocation concealment, several at unclear or high risk of attrition bias, none clearly had blinded outcome assessment, moreover sensitivity analysis restricted to five studies with clear description of allocation concealment results in a non‐significant effect (OR 1.38, 95% CI 0.96 to 1.99).
2Downgraded one level for serious risk of bias: several studies did not describe acceptable methods of sequence generation and/or allocation concealment, several at unclear or high risk of attrition bias, none clearly had blinded outcome assessment.
3Downgraded one level for serious imprecision: findings compatible with benefit in either group or with no effect.
4Downgraded one level for serious inconsistency.

Figuras y tablas -
Summary of findings for the main comparison. Blastocyst stage versus cleavage stage embryo transfer for assisted reproductive technology
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 1998

Single Hams F10 In‐house

Sequential G1/G2 In‐house

Hreinsson 2004

Vitrolife IVF

Sequential G1/G2 or CCM Vitrolife

Karaki 2002

Medicult

Sequential G1/G2 Vitrolife

Kaur 2014

Cleavage medium

G2 Plus media

Kolibianakis 2004

Sequential G1 Vitrolife

Sequential G1/G2 Vitrolife

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

Ten 2011

NS

NS

Van der Auwera 2002

Sequential both Cook and Vitrolife

Sequential both Cook and Vitrolife

CCM ‐ it is a trade mark from Vitrolife of medium for blastocyst culture
IVF ‐ in vitro fertilisation
NS ‐ not stated
G1/G2 ‐ sequential media from Vitrolife

Figuras y tablas -
Table 1. Culture techniques of included studies
Table 2. Blastocyst and implantation rate (in day 5 to 6 transfers)

Study

Blastocyst 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 patients had only 1 blastocyst

Coskun 2000

28%

50/235; 21.3%

52/218; 23.9%

77% patients 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 1998

46.5%

64/174; 36.8%

53/95; 55.8%

85% women had at least 2 blastocysts

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)

Kaur 2014

Not stated

66/309; 21.4%

102/290; 35.2%

Kolibianakis 2004

50.7%

96/234; 41.0%

94/226; 41.6%

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 patients 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

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)

Figuras y tablas -
Table 2. Blastocyst and implantation rate (in day 5 to 6 transfers)
Table 3. Mean number of embryos transferred

Study ID

Day 2/3

Day 5/6

Aziminekoo 2015

2.8

2.6

Brugnon 2010

1

1

Bungum 2003

2.00

1.97

Coskun 2000

2.3

2.2

Devreker 2000

2.83

1.73

Elgindy 2011

2.8

1.97

Emiliani 2003

2.1

1.9

Fernandez‐Shaw 2015

1.5

1.4

Fisch 2007

1

1

Frattarelli 2003

2.96

2.04

Gaafar 2015

NS

NS

Gardner 1998

3.7

2.2

Hreinsson 2004

1.8

1.9

Karaki 2002

3.5

2.0

Kaur 2014

2.04

1.93

Kolibianakis 2004

1.9

1.8

Levitas 2004

3.4

1.9

Levron 2002

3.1

2.3

Livingstone 2002

2.0

1.0

Motta 1998

4.6

2.3

Pantos 2004

4

3.4

Papanikolaou 2005

2

1.97

Papanikolaou 2006

1

1

Rienzi 2002

2.0

2.0

Schillaci 2002

2.8

1.8

Ten 2011

2

2

Van der Auwera 2002

1.86

1.87

NS ‐ not stated

Figuras y tablas -
Table 3. Mean number of embryos transferred
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 Live birth per couple Show forest plot

13

1630

Odds Ratio (M‐H, Fixed, 95% CI)

1.48 [1.20, 1.82]

2 Live birth per couple: grouped by number of embryos transferred Show forest plot

12

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 More cleavage stage than blastocyst embryos transferred

6

483

Odds Ratio (M‐H, Fixed, 95% CI)

1.51 [1.03, 2.22]

2.2 Single embryo transfer

2

458

Odds Ratio (M‐H, Fixed, 95% CI)

1.47 [0.98, 2.20]

2.3 Equal number of embryos transferred

6

1027

Odds Ratio (M‐H, Fixed, 95% CI)

1.35 [1.04, 1.75]

3 Live birth rate per couple: grouped by prognosis Show forest plot

13

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 good prognostic factors

8

1126

Odds Ratio (M‐H, Fixed, 95% CI)

1.51 [1.18, 1.93]

3.2 poor prognostic factors

2

77

Odds Ratio (M‐H, Fixed, 95% CI)

2.05 [0.53, 7.96]

3.3 unselected group

3

427

Odds Ratio (M‐H, Fixed, 95% CI)

1.36 [0.91, 2.02]

4 Live birth rate: grouped by day of randomisation Show forest plot

13

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 randomisation at start of cycle

5

819

Odds Ratio (M‐H, Fixed, 95% CI)

1.26 [0.93, 1.70]

4.2 randomised on day of OPU and day 1 after OPU

4

365

Odds Ratio (M‐H, Fixed, 95% CI)

1.34 [0.87, 2.06]

4.3 randomised day 2 to 3 post‐OPU

2

364

Odds Ratio (M‐H, Fixed, 95% CI)

2.17 [1.42, 3.33]

4.4 day of randomisation unstated

2

82

Odds Ratio (M‐H, Fixed, 95% CI)

1.71 [0.67, 4.39]

Figuras y tablas -
Comparison 1. Blastocyst versus cleavage stage transfer: Live birth rate following fresh transfer
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

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 Cumulative pregnancy rate per couple: grouped by number of embryos transferred Show forest plot

4

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 single embryo transfer

1

107

Odds Ratio (M‐H, Fixed, 95% CI)

0.84 [0.39, 1.79]

2.2 equal number of embryos transferred

4

512

Odds Ratio (M‐H, Fixed, 95% CI)

0.69 [0.48, 0.99]

3 Cumulative pregnancy rate per couple: grouped by prognosis Show forest plot

5

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 good prognostic factors

2

205

Odds Ratio (M‐H, Fixed, 95% CI)

0.54 [0.30, 0.98]

3.2 unselected group

3

427

Odds Ratio (M‐H, Fixed, 95% CI)

1.10 [0.74, 1.61]

4 Cumulative pregnancy rate: grouped by day of randomisation Show forest plot

5

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 randomisation at start of cycle

3

414

Odds Ratio (M‐H, Fixed, 95% CI)

0.81 [0.54, 1.20]

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]

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

5.1 slow freezing

4

512

Odds Ratio (M‐H, Fixed, 95% CI)

0.69 [0.48, 0.99]

5.2 vitrification

1

120

Odds Ratio (M‐H, Fixed, 95% CI)

2.44 [1.17, 5.12]

Figuras y tablas -
Comparison 2. Blastocyst versus cleavage stage transfer: Cumulative pregnancy rate following fresh and frozen transfer
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

1 Clinical pregnancy rate per couple Show forest plot

27

4031

Odds Ratio (M‐H, Fixed, 95% CI)

1.30 [1.14, 1.47]

2 Clinical pregnancy rate per couple: grouped by number of embryos transferred Show forest plot

23

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 equal numbers of embryo transfers

11

1854

Odds Ratio (M‐H, Fixed, 95% CI)

1.19 [0.99, 1.44]

2.2 more cleavage stage than blastocyst embryos transferred

12

1387

Odds Ratio (M‐H, Fixed, 95% CI)

1.07 [0.86, 1.33]

2.3 single embryo transfer

3

478

Odds Ratio (M‐H, Fixed, 95% CI)

1.24 [0.84, 1.82]

3 Clinical pregnancy rate per couple: grouped by prognosis Show forest plot

27

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 good prognostic factors

15

2056

Odds Ratio (M‐H, Fixed, 95% CI)

1.30 [1.09, 1.56]

3.2 poor prognostic factors

3

195

Odds Ratio (M‐H, Fixed, 95% CI)

1.62 [0.84, 3.10]

3.3 unselected group

9

1780

Odds Ratio (M‐H, Fixed, 95% CI)

1.26 [1.04, 1.53]

4 Clinical pregnancy rate per couple: grouped by day of randomisation Show forest plot

25

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 randomised start of cycle

7

1371

Odds Ratio (M‐H, Fixed, 95% CI)

1.19 [0.95, 1.49]

4.2 randomised on day of OPU or day 1

10

1130

Odds Ratio (M‐H, Fixed, 95% CI)

1.15 [0.90, 1.46]

4.3 randomised on day 2 to 3

4

537

Odds Ratio (M‐H, Fixed, 95% CI)

1.59 [1.13, 2.23]

4.4 day of randomisation unstated

4

441

Odds Ratio (M‐H, Fixed, 95% CI)

0.84 [0.57, 1.25]

Figuras y tablas -
Comparison 3. Blastocyst versus cleavage stage transfer: Clinical pregnancy following fresh transfer
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

1 Multiple pregnancy rate per couple Show forest plot

19

3019

Odds Ratio (M‐H, Fixed, 95% CI)

1.05 [0.83, 1.33]

2 Multiple pregnancy rate per couple: grouped by number of embryo transfer Show forest plot

16

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 equal number of embryos transferred

8

1672

Odds Ratio (M‐H, Fixed, 95% CI)

1.05 [0.75, 1.46]

2.2 more cleavage stage than blastocyst embryos transferred

8

809

Odds Ratio (M‐H, Fixed, 95% CI)

0.75 [0.49, 1.13]

2.3 single embryo transfer

1

351

Odds Ratio (M‐H, Fixed, 95% CI)

0.20 [0.01, 4.17]

3 Multiple pregnancy rate per couple: grouped by prognosis Show forest plot

18

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 good prognostic factors

12

1798

Odds Ratio (M‐H, Fixed, 95% CI)

1.10 [0.83, 1.48]

3.2 poor prognostic factors

1

54

Odds Ratio (M‐H, Fixed, 95% CI)

0.89 [0.14, 5.81]

3.3 unselected

5

1049

Odds Ratio (M‐H, Fixed, 95% CI)

0.98 [0.65, 1.48]

4 Multiple pregnancy rate per couple: grouped by day of randomisation Show forest plot

17

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 randomised start of cycle

5

1172

Odds Ratio (M‐H, Fixed, 95% CI)

0.94 [0.59, 1.48]

4.2 randomised on day of OPU or day 1

7

846

Odds Ratio (M‐H, Fixed, 95% CI)

0.91 [0.60, 1.38]

4.3 randomised on day 2 to 3

3

382

Odds Ratio (M‐H, Fixed, 95% CI)

1.31 [0.79, 2.19]

4.4 day of randomisation unstated

2

175

Odds Ratio (M‐H, Fixed, 95% CI)

0.21 [0.06, 0.70]

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]

Figuras y tablas -
Comparison 4. Blastocyst versus cleavage stage transfer: Multiple pregnancy following fresh transfer
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

1 Miscarriage rate per couple Show forest plot

18

2917

Odds Ratio (M‐H, Fixed, 95% CI)

1.15 [0.88, 1.50]

Figuras y tablas -
Comparison 5. Blastocyst versus cleavage stage transfer: Miscarriage rate following fresh transfer
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

1 Embryo freezing per couple Show forest plot

14

2292

Odds Ratio (M‐H, Fixed, 95% CI)

0.48 [0.40, 0.57]

Figuras y tablas -
Comparison 6. Blastocyst versus cleavage stage transfer: Embryo freezing rate per couple
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

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]

Figuras y tablas -
Comparison 7. Blastocyst versus cleavage stage transfer: Failure rate to transfer embryos (per couple)