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Effect(s) of assisted hatching on assisted conception (IVF & ICSI)

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Referencias

References to studies included in this review

Antinori 1996A {published data only}

Antinori S, Panci C, Selman HA, Caffa B, Dani G, Versaci C. Zona thinning with the use of laser: a new approach to assisted hatching in humans. Human Reproduction 1996;11(3):590‐4.

Antinori 1996B {published data only}

Antinori S, Panci C, Selman HA, Caffa B, Dani G, Versaci C. Zona thinning with the use of laser: a new approach to assisted hatching in humans. Human Reproduction 1996;11(3):590‐4.

Antinori 1996C {published data only}

Antinori S, Selman HA, Caffa B, Panci C, Dani GL, Versaci C. Zona opening of human embryos using a non‐contact UV laser for assisted hatching in patients with poor prognosis of pregnancy. Human Reproduction 1996;11(11):2488‐92.

Antinori 1999A {published data only}

Antinori S, Versaci C, Dani L, Barbaro E, Antinori M, Cerusico C, Vidali A. Laser assisted hatching at the extremes of the IVF spectrum: first cycle and after 6 cycles. A randomized prospective trial [abstract]. Fertility and Sterility 1999;72(3, suppl 1):S111.

Antinori 1999B {published data only}

Antinori S, Versaci C, Dani L, Barbaro E, Antinori M, Cerusico C, Vidali A. Laser assisted hatching at the extremes of the IVF spectrum: first cycle and after 6 cycles. A randomized prospective trial [abstract]. Fertility and Sterility 1999;72(3, suppl 1):S111.

Baruffi 2000 {published data only}

Baruffi RL, Mauri AL, Petersen CG, Ferreira RC, Coelho J, Franco JG. Zona thinning with noncontact diode laser in patients aged < or = 37 years with no previous failure of implantation: a prospective randomized study. Journal of Assisted Reproduction and Genetics 2000;17(10):557‐60.

Chao 1997 {published data only}

Chao KH, Chen SU, Chen HF, Wu MY, Yang YS, Ho HN. Assisted hatching increases the implantation and pregnancy rate of in vitro fertilization (IVF)‐embryo transfer (ET), but not that of IVF‐tubal ET in patients with repeated IVF failures. Fertility & Sterility 1997;67(5):904‐8.

Cohen 1992A {published data only}

Cohen J, Alikani M, Trowbridge J, Rosenwaks Z. Implantation enhancement by selective assisted hatching using zona drilling of human embryos with poor prognosis. Human Reproduction 1992;7(5):685‐91.
Liu H‐C, Alikani M, Cohen J, Rosenwaks Z. Assisted hatching facilitaties earlier implantation after IVF‐ET. Fertility and Sterility Abstracts. 1992; Vol. 58:61 (O‐136).
Liu H‐C, Cohen J, Alikani M, Noyes N, Rosenwaks Z. Assisted hatching facilitates earlier implantation. Fertility and Sterility 1993;60(5):871‐5.

Cohen 1992B {published data only}

Cohen J, Alikani M, Trowbridge J, Rosenwaks Z. Implantation enhancement by selective assisted hatching using zona drilling of human embryos with poor prognosis. Human Reproduction 1992;7:685‐91.
Liu H‐C, Alikani M, Cohen J, Rosenwaks Z. Assisted hatching facilitates earlier implantation after IVF‐ET. Fertility and Sterility Abstracts. 1992; Vol. 58:61 (O‐136).

Hellebaut 1996 {published and unpublished data}

Hellebaut S, De Sutter P, Dozortsev D, Onghena A, Qian C, Dhont M. Does assisted hatching improve implantation rates after in vitro fertilization or intracytoplasmic sperm injection in all patients? A prospective randomized study. Journal of Assisted Reproduction & Genetics 1996;13(1):19‐22.

Hurst 1998 {published and unpublished data}

Hurst BS, Tucker KE, Awoniyi CA, Schlaff WD. Assisted hatching does not enhance IVF success in good‐prognosis patients. Journal of Assisted Reproduction & Genetics 1998;15(2):62‐4.

Isik 2000 {published data only}

Isik AZ, Vicdan K, Kaba A, Dagli G. Comparison of zona manipulated and zona intact blastocyst transfers: a prospective randomized trial. Journal of Assisted Reproduction and Genetics 2000;17(3):135‐9.

Isiklar 1999 {published data only}

Isiklar A, Balaban B, Aksoy S, Alatas C, Mercan R, Nuhoglu A, et al. The effect of mechanical assisted hatching on progression of cleavage stage embryos to the blastocyst stage [abstract]. Fertility and Sterility 1999;72(3, suppl 1):S162.

Laffoon 1999 {published data only}

Laffoon IS, Sokoloski JE, Volk EA, Hughes L, Krivinko DM, Sanfilippo JS, et al. The effect of assisted hatching on the outcome of assisted reproductive technology cycles in women under 39 years of age [abstract]. Fertility and Sterility 1999;72(3, suppl 1):S243.

Lanzendorf 1998 {published and unpublished data}

Lanzendorf SE, Nehchiri F, Mayer JF, Oehninger S, Muasher SJ. A prospective, randomized, double‐blind study for the evaluation of assisted hatching in patients with advanced maternal age. Human Reproduction 1998;13(2):409‐13.

Mansour 2000A {published data only}

Mansour RT, Rhodes CA, Aboulghar MA, Serour GI, Kamal A. Transfer of zona‐free embryos improves outcome in poor prognosis patients: a prospective randomized controlled study. Human Reproduction 2000;15(5):1061‐4.

Mansour 2000B {published data only}

Mansour RT, Rhodes CA, Aboulghar MA, Serour GI, Kamal A. Transfer of zona‐free embryos improves outcome in poor prognosis patients: a prospective randomized controlled study. Human Reproduction 2000;15(5):1061‐4.

Nagy 1999 {published data only}

Nagy ZP, Rienzi L, Iacobelli M, Morgia F, Ubaldi F, Schimberni M, et al. Laser‐assisted hatching and removal of degenerated blastomere(s) of frozen‐thawed embryos improves pregnancy rate [abstract]. Fertility and Sterility 1999;72(3, suppl 1):S4.

Olivennes 1997 {published and unpublished data}

Olivennes F, Hazout AD. A prospective randomized study of the use of assisted hatching in IVF‐ET patients with high day‐3 FSH. Increased clinical pregnancy rate with assisted hatching but high rate of miscarriages. Fertility & Sterility. Abstracts of the meeting of American Society for Reproductive Medicine 1997:S226.

Ryan 1997 {published data only}

Ryan JP, Pike IL, Catt JW, Porter RN, Saunders DM. Failure of assisted hatching to increase pregnancy rates following the transfer of fresh or frozen‐thawed day 2 human embryos. Human Reproduction Abstracts of 13th Annual Meeting of the ESHRE 1997:188.

Stein 1995 {published data only}

Stein A, Rufas O, Amit S, Avrech O, Pinkas H, Ovadia J, et al. Assisted hatching by partial zona dissection of human pre‐embryos in patients with recurrent implantation failure after in vitro fertilization. Fertility & Sterility 1995;63(4):838‐41.

Tucker 1993 {published data only}

Tucker MJ, Luecke NM, Wiker SR, Wright G. Chemical removal of the outside of the zona pellucida of day 3 human embryos has no impact on implantation rate. Journal of Assisted Reproduction & Genetics 1993;10(3):187‐91.

Tucker 1996 {published data only}

Tucker MJ, Morton PC, Wright G, Ingargiola PE, Sweitzer CL, Elsner CW, et al. Enhancement of outcome from intracytoplasmic sperm injection: does co‐culture or assisted hatching improve implantation rates?. Human Reproduction 1996;11(11):2434‐7.

References to studies excluded from this review

Balaban 2002 {published data only}

Balaban B, Urman B, Alatas C, Mercan R, Mumcu A, Isiklar A. A comparison of four different techniques of assisted hatching. Human Reproduction 2002;17:1239‐43.

Bider 1997 {published data only}

Bider D, Livshits A, Yonish M, Yemini Z, Mashiach S, Dor J. Assisted hatching by zona drilling of human embryos in women of advanced age. Human Reproduction 1997;12:317‐20.

Blake 2001 {published data only}

Blake CA, Forsberg AS, Johansson BR, Wikland M. Laser zona pellucida thinning ‐ an alternative approach to assisted hatching. Human Reproduction 2001;16(9):1959‐64.

Check 1996 {published data only}

Check JH, Hoover L, Nazari A, O'Shaughnessy A, Summers D. The effect of assisted hatching on pregnancy rates after frozen embryo transfer. Fertility & Sterility 1996;65:254‐7.

Chen 1999 {published data only}

Chen C, Kattera S, Lim MN. Improved pregnancy rates in assisted reproduction using assisted hatching and delayed embryo transfer. Proceedings of the 11th World Congress on In Vitro Fertilization & Human Reproductive Genetics, Bologna, Italy. Monduzzi, 1999:169‐72.

Cieslak 1999 {published data only}

Cieslak J, Ivakhnenko V, Wolf G, Sheleg S, Verlinsky Y. Three‐dimensional partial zona dissection for preimplantation genetic diagnosis and assisted hatching. Fertility and Sterility 1999;71(2):308‐13.

Cohen 1990 {published data only}

Cohen J, Elsner C, Kort H, Malter H, Massey J, Mayer MP, et al. Impairment of the hatching process following IVF in the human and improvement of implantation by assisting hatching using micromanipulation. Human Reproduction 1990;5(1):7‐13.

Dokras 1994 {published data only}

Dokras A, Ross C, Gosden B, Sargent IL, Barlow DH. . Micromanipulation of human embryos to assist hatching. Fertil Steril 1994, 61: 514 ‐ 520.. Fertility & Sterility 1994;61:514‐20.

Domitrz 2000 {published data only}

Domitrz J, Wolczynski S, Syrewicz M, Kuczynski W, Szamatowicz J, Grochowski D, et al. Enzymatic assisted hatching in the infertile couple after failed attempts IVF ET. Ginekol Pol 2000, 71: 1047 1052. [In Polish]. Ginekologia Polska 2000;71:1047‐52.

Ebner 2002 {published data only}

Ebner T, Moser M, Yaman C, Sommergruber M, Hartl J, Jesacher K, et al. Prospective hatching of embryos developed from oocytes exhibiting difficult oolemma penetration during ICSI. Human Reproduction 2002;17:1317‐20.

Edirisinghe 1999 {published data only}

Edirisinghe WR, Ahnonkitpanit V, Promviengchai S, Suwajanakorn S, Pruksananonda K, Chinpilas V, et al. A study failing to determine significant benefits from assisted hatching: patients selected for advanced age, zonal thickness of embryos, and previous failed attempts. Journal of Assisted Reproduction & Genetics 1999;16:294‐301.

Hershlag 1999 {published data only}

Hershlag A, Paine T, Cooper GW, Scholl GM, Rawlinson K, Kvapil G. Monozygotic twinning associated with mechanical assisted hatching. Fertility and Sterility 1999;71(1):144‐6.

Huttelova 1999 {published data only}

Huttelova R, Becvarova V, Mardesic T, Muller P, Hulvert J, Voboril J. Assisted hatching combined with long‐term culture. Proceedings of the 11th World Congress on In Vitro Fertilization & Human Reproductive Genetics, Bologna, Italy. Monduzzi, 1999:169‐72.

Lee 1999 {published data only}

Lee JE, Lee DR, Paik HR, Shim HN, Cho JH, Roh SI, Yoon HS. Biochemical assisted hatching (BAH) increased the implantation and pregnancy rate in human cryopreserved embryo transfer [abstract]. Fertility and Sterility 1999;72(3, Suppl 1):S4‐S5.

Magli 1998A {published and unpublished data}

Magli MC, Gianaroli L, Ferraretti AP, Fortini D, Aicardi G, Montanaro N. Rescue of implantation potential in embryos with poor prognosis by assisted zona hatching. Human Reproduction 1998;13(5):1331‐5.

Magli 1998B {published and unpublished data}

Magli MC, Gianaroli L, Ferraretti AP, Fortini D, Aicardi G, Montanaro N. Rescue of implantation potential in embryos with poor prognosis by assisted zona hatching. Human Reproduction 1998;13(5):1331‐5.

Magli 1998C {published and unpublished data}

Magli MC, Gianaroli L, Ferraretti AP, Fortini D, Aicardi G, Montanaro N. Rescue of implantation potential in embryos with poor prognosis by assisted zona hatching. Human Reproduction 1998;13(5):1331‐5.

Mahadevan 1998 {published data only}

Mahadevan MM, Miller MM, Maris MO, Moutos D. Assisted hatching of embryos by micromanipulation for human in vitro fertilization: UAMS experience. Jornal of the Arkansas Medical Society 1998;94:529‐31.

Meldrum 1998 {published data only}

Meldrum DR, Wisot A, Yee B, Garzo G, Yeo L, Hamilton F. Assisted hatching reduces the age‐related decline in IVF outcome in women younger than age 43 without increasing miscarriage or monozygotic twinning. Journal of Assisted Reproduction & Genetics 1998;15:418‐21.

Montag 1999 {published data only}

Montag M, van der Ven H. Laser‐assisted hatching in assisted reproduction. Croatian Medical Journal 1999;40:398‐403.

Nakayama 1998 {published data only}

Nakayama T, Fujiwara H, Tastumi K, Fujita K, Higuchi T, Mori T. A new assisted hatching technique using a piezo‐micromanipulator. Fertility and Sterility 1998;69(4):784‐8.

Nakayama 1999 {published data only}

Nakayama T, Fujiwara H, Yamada S, Tastumi K, Honda T, Fujii S. Clinical application of a new assisted hatching method using piezo‐micromanipulator for morphologically low‐quality embryos in poor‐prognosis infertile patients. Fertility and Sterility 1999;71(6):1014‐8.

Obruca 1994 {published data only}

Obruca A, Strohmer H, Sakkas D, Menezo Y, Kogosowski A, Barak Y. Use of lasers in assisted fertilization and hatching. Human Reproduction 1994;9:1723‐6.

Ringler 1999 {published data only}

Ringler GE, Marrs RP, Stein AL, Varygas JM, Schiewe MC. Improved pregnancy rates using assisted hatching on day 3 frozen‐thawed embryos [abstract]. Fertility and Sterility 1999;72(3, Suppl 1):S86.

Schoolcraft 1994 {published data only}

Schoolcraft WB, Schlenker T, Gee M, Jones GS, Jones HW. Assisted hatching in the treatment of poor prognosis in vitro fertilization candidates. Fertility and Sterility 1994;62(3):551‐4.

Szell 1998 {published data only}

Szell AZ, Antaran JM, Chetkowski RJ. Pregnancy and implantation rates from the transfer of human embryos cultured in P1 or human tubal fluid medium and transferred with or without assisted hatching. Fertility & Sterility 1998;70:S495.

Tao 1997 {published data only}

Tao J, Tamis R. Application of assisted hatching for 2‐day‐old, frozen‐thawed embryo transfer in a poor prognosis population. Journal of Assisted Reproduction and Genetics 1997;14(2):128‐30.

Tucker 1991 {published data only}

Tucker MJ, Cohen J, Massey JB, Mayer MP, Wiker SR, Wright G. Partial dissection of the zona pellucida of frozen‐thawed human embryos may enhance blastocyst hatching, implantation and pregnancy rates. American Journal of Obstetrics and Gynecology 1991;165(2):342‐5.

Utsunomiya 1998 {published data only}

Utsunomiya T, Sato M, Hirotsuru K. Assisted hatching by zona thinning to multiple‐failure in vitro fertilization patients [abstract]. Fertility and Sterility 1998;70(3, Suppl 1):S328.

Zech 1998 {published data only}

Zech H, Stecher A, Vanderzwalmen P, Murach KF. Investigation of the usefulness of laser‐assisted hatching for women of ages above and below forty years [abstract]. Fertility and Sterility 1998;70(3, Suppl 1):S428.

References to ongoing studies

Germond 1998 {published data only}

Germond M, Primi M‐P, Senn A, Pannatier A, Rink K, Delacretaz G, et al. Diode laser for assisted hatching: preliminary results of a multicentric prospective randomized study. Human Reproduction 1998;13:84‐5.

Al‐Nuaim 2002

Al‐Nuaim LA, Jenkins JM. Assisted hatching in assisted reproduction. British Journal of Obstetrics & Gynaecology August 2002;109:856‐62.

Bleil 1980

Bleil JD, Wasserman PM. Strucutre and function of the zona pellucida: Identification and characterisation of the proteins of the mouse oocyte zona pellucida. Developmental Biology 1980;76:185‐202.

Bronson 1970

Bronson RA, McLaren A. Transfer to mouse oviduct of eggs with and without the zona pellucida. Journal of Reprodctive Fertility 1970;22:129‐36.

Check 1999

Check JH, Choe JK, Katsoff D, Summers‐Chase D, Wilson C. Controlled ovarian hyperstimulation adversely affects implantation following in vitro fertilization‐embryo transfer. Journal of Assisted Reproduction & Genetics 1999;16(8):416‐20.

Cohen 1991

Cohen J. Assisted hatching of human embryos. Journal of in Vitro Fertilization & Embryo Transfer 1991;8(4):179‐90.

Cole 1967

Cole RJ. Cinematographic observation on the trophoblast and zona pellucida of the mouse blastoccyst. Journal of Embryology Experimental Morphology 1967;17:481‐90.

da Costa 2001

da Costa ALE, Abdelmassih S, de Oliveira FG, Abdelmassih V, Abdelmassih R, Nagy ZP, et al. Monozygotic twins and transfer at the blastocyst stage after ICSI. Human Reproduction 2001;16(2):333‐6.

Denker 1993

Denker HW. Implantation: a cell biological paradox. Journal of Experimental Zoology 1993;266:541‐58.

Fehilly 1985

Fehilly CB, Cohen J, Simons RF, Fishel SB, Edwards RG. Cryopreservation of cleaving embryos and expanded blastocysts in the human: a comparative study. Fertility & Sterility 1985;44:638‐44.

Gardner 2000

Gardner DK, Lane M, Schoolcraft WB. Culture and transfer of viable blastocysts: a feasible proposition for human IVF. Hum Reprod 2000;15(Suppl 6):9‐23.

Harlow 1982

Harlow GM, Quinn P. Development of pre‐implantation mouse embryos in vitro and in vivo. Aust J Biol Sci 1982;35:187‐93.

HFEA 2000

Human Fertilisation, Embryology Authority (UK). Patient's Guide to IVF Clinics 2000. London: The HFEA, 2000.

Hsu 1999

Hsu MI, Mayer J, Aronshon M, Lazendorf S, Muasher S, Kolm P, Oehninger S. Embryo implantation in in vitro fertilization and intracytoplasmic sperm injection: impact of cleavage status, morphology grade, and number of embryos transferred. Fertility & Sterility 1999;72(4):679‐85.

Lopata 1996

Lopata A. Implantation of the human embryo. Human Reproduction 1996;11(Suppl 1):175‐84.

Loret de Mola 1997

Loret De Mola JR, Garside WT, Bucci J, Tureck RW, Heyner S. Analysis of the human zona pellucida during culture: correlation with diagnosis and the preovulatory hormonal environment. Journal of Assisted Reproduction & Genetics 1997;14:332‐7.

Mercader 2001

Mercader A, Simon C, Galan A, Herrer R, Albert C, Remohi J, et al. An analysis of spontaneous hatching in a human endometrial epithelial coculture system: is assisted hatching justified?. Journal of Assisted Reproduction & Genetics 2001;18(6):315‐9.

Rink 1995

Rink K, Descloux L, Delacretaz G, Senn A, Nocera D, Germond M. Zona pellucida drilling by a 1.48um laser: influence on the biomechanics of the hatching process [abstract]. SPIE ‐ The International Society for Optical Engineering Proceedings, Barcelona 1995:2624.

Sengoku 2000

Sengoku K. Present state and future in reproductive medicine. Hokkaido Igaku Zasshi 2000;75(4):237‐42.

Spandorfer 2000

Spandorfer SD, Chung PH, Kligman I, Liu HC, Davis OK, Rosenwaks Z. An analysis of the effect of age on implantation rates. Journal of Assisted Reproduction & Genetics 2000;17(6):303‐6.

WHO 1975

World Health Organisation. The epidemiology of infertility. Vol. 582, World Health Organization Technical Report Service, 1975:1‐37.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Antinori 1996A

Methods

Randomisation stated, but method unclear or incorrect.
Allocation concealment unclear.
Single centre.
Participants not blinded or unclear
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from Italy with repeated implantation failure and zona thickness >12 um undergoing IVF. Mean age control 34.8 (5.1), AH 34.6 (5.2).

Interventions

AH (laser; partial zona breach; 48 hours egg retrieval to AH; 0 hours AH to transfer) versus no AH
AH: 104 women randomised, 376 embryos transferred
control: 104 women randomised, 381 embryos transferred

Outcomes

implantation, clinical pregnancy, miscarriage, multiple pregnancy

Notes

Attempted to contact author about this study, no reply received

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Antinori 1996B

Methods

Randomisation stated, but method unclear or incorrect. Allocation concealment unclear.
Single centre.
Participants not blinded or unclear
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from Italy (first IVF treatment) with zona thickness >12 um undergoing IVF. Mean age control 34.6 (5.2), AH 34.4 (5.1).

Interventions

AH (laser; partial zona breach; 48 hours egg retrieval to AH; 0 hours AH to transfer) versus no AH
AH: 104 women randomised, 397 embryos transferred
control: 121 women randomised, 411 embryos transferred

Outcomes

implantation, clinical pregnancy, miscarriage, multiple pregnancy

Notes

Attempted to contact author about this study, no reply received

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Antinori 1996C

Methods

Randomised, method stated. Allocation concealment unclear.
Single centre.
Participants not blinded or unclear
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from Italy with repeated (2‐4 previous) implantation failure and zona thickness >12 um undergoing IVF. Mean age control 37.8 (1.5), AH 38.2 (1.3).

Interventions

AH (laser; complete zona breach; ? hours egg retrieval to AH; 0 hours AH to transfer) versus no AH
AH: 72 women randomised, 218 embryos transferred
control: 98 women randomised, 407 embryos transferred

Outcomes

implantation, clinical pregnancy, miscarriage, multiple pregnancy

Notes

Attempted to contact author about this study, no reply received

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Antinori 1999A

Methods

Randomisation stated, but method unclear or incorrect.
Allocation concealment unclear.
Single/multi‐centre?
Participants not blinded or unclear
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as abstract.

Participants

Women from Italy without previous IVF experience undergoing IVF. Mean age control 27.0, AH 27.5.

Interventions

AH (laser; complete zona breach; ? hours egg retrieval to AH;? hours AH to transfer) versus no AH
AH: 96 women randomised, 221 embryos transferred (estimated)
control: 103 women randomised, 247 embryos transferred (estimated)

Outcomes

clinical pregnancy, miscarriage, multiple pregnancy

Notes

No attempt to contact author about this study

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Antinori 1999B

Methods

Randomisation stated, but method unclear or incorrect. Allocation concealment unclear.
Single/ multi‐centre?
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as abstract.

Participants

Women from Italy with >6 previous IVF failures undergoing IVF. Mean age control 36.0, AH 37.5.

Interventions

AH (laser; complete zona breach; ? hours egg retrieval to AH;? hours AH to transfer) versus no AH
AH: 73 women randomised, 321 embryos transferred
control: 69 women randomised, 307 embryos transferred

Outcomes

clinical pregnancy, miscarriage, multiple pregnancy

Notes

No attempt to contact author about this study

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Baruffi 2000

Methods

Randomised, method stated. Allocation concealment unclear.
Single centre.
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear.
Published as full paper.

Participants

Women from Brazil aged 37 years or less, undergoing ICSI for the first time (mean zona thickness control 17.1 um (sd 1.7), AH 16.6 um (sd 2.2). Mean age control 31.4 (3.6), AH 31.8 (3.6).

Interventions

AH (laser; partial zona breach; 48 hours egg retrieval to AH; 0 hours AH to transfer) versus no AH
AH: 51 women randomised, 141 embryos transferred
control: 52 women randomised, 149 embryos transferred

Outcomes

implantation, clinical pregnancy, miscarriage

Notes

No attempt to contact author about this study

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Chao 1997

Methods

Randomised, method stated. Allocation concealment unclear.
Single centre.
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from Taiwan with repeated IVF failure, undergoing IVF. (Mean basal FSH levels control 6.9 (2.9), AH 6.7 (2.4) IU/L). Mean age control 34.0 (3.9), AH 36.5 (5.2).

Interventions

AH (mechanical; complete zona breach; 48 hours egg retrieval to AH; 4‐6 hours AH to transfer) versus no AH
AH: 33 women randomised, 155 embryos transferred
control: 31 women randomised, 134 embryos transferred

Outcomes

implantation

Notes

Attempted to contact author about this study, no reply received

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Cohen 1992A

Methods

Randomised, method stated. Allocation concealment inadequate.
Single centre.
Participants blinded.
Assessor blinded.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from North America undergoing IVF, normal 3 day FSH levels (15IU/L or less). Mean age control 36.7 (3.7), AH 36.5 (3.3).

Interventions

AH by acid tyrodes (chemical; complete zona breach; 68‐72 hours egg retrieval to AH; 4‐8 hours AH to transfer) versus no AH
AH: 69 women randomised, 239 embryos transferred
control: 68 women randomised, 229 embryos transferred

Outcomes

implantation, clinical pregnancy, live births, multiple pregnancy

Notes

Attempted to contact author about this study. Reply received, but no additional information was offered.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

High risk

C ‐ Inadequate

Cohen 1992B

Methods

Randomised, method stated. Allocation concealment inadequate.
Single centre.
Participants blinded.
Assessor blinded.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from North America undergoing IVF, high basal FSH ( >15IU/L). Mean age not stated.

Interventions

AH by acid tyrodes (chemical; complete zona breach; 68‐72 hours egg retrieval to AH; 4‐8 hours AH to transfer) versus no AH
AH: 15 women randomised, 38 embryos transferred
control: 15 women randomised, 41 embryos transferred

Outcomes

implantation, clinical pregnancy

Notes

Attempted to contact author about this study. Reply received, but no additional information was offered.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

High risk

C ‐ Inadequate

Hellebaut 1996

Methods

Randomised, method stated. Allocation concealment inadequate.
Single centre.
Participants not blinded
Assessor not blinded.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from Belgium undergoing IVF or ICSI. Mean age control 30.8 (3.9), AH 30.9 (4.3).

Interventions

AH (mechanical; complete zona breach; 48 hours egg retrieval to AH; 0.2 hours AH to transfer) versus no AH
AH: 60 women randomised, 168 embryos transferred
control: 60 women randomised, 162 embryos transferred

Outcomes

implantation, clinical pregnancy, live births, miscarriage, ectopic pregnancy

Notes

Attempted to contact author about this study. A reply including much useful additional information was received.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

High risk

C ‐ Inadequate

Hurst 1998

Methods

Randomised, method stated. Allocation concealment unclear.
Single centre.
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from North America undergoing IVF either with no prior IVF (30 years or less, FSH<10IU/L, normal endometrium and sperm) or prior IVF (35 years or less, 6 embryos, 50% fertilisation, normal endometrium). Mean age control 30 (2.1), AH 30 (3.2).

Interventions

AH by acid tyrodes (chemical; complete zona breach; ? hours egg retrieval to AH; ? hours AH to transfer) versus no AH
AH: 13 women randomised, 52 embryos transferred
control: 7 women randomised, 28 embryos transferred

Outcomes

implatation, clinical pregnancy, live births

Notes

Attempted to contact author about this study. A reply including much useful additional information was received.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Isik 2000

Methods

Randomised, method stated. Allocation concealment unclear.
Single centre.
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from Turkey with >5 day‐3 cleavage stage embryos (FSH at day‐3 control 6.1 (3.0), AH 5.5 (1.4) IU/L, mean duration of infertility 6.7 years) undergoing ICSI. Mean age control 29.1 (3.6), AH 30.5 (5.2).

Interventions

AH enzymatic (chemical; complete zona breach; 120‐144 hours egg retrieval to AH; 0.5‐1 hours AH to transfer) versus no AH
AH: 24 women randomised, 71 embryos transferred
control: 22 women randomised, 63 embryos transferred

Outcomes

implantation

Notes

No attempt to contact author about this study

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Isiklar 1999

Methods

Randomisation stated, but method unclear or incorrect. Allocation concealment unclear.
Single centre.
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as abstract.

Participants

Women from Turkey undergoing IVF. Mean age not stated.

Interventions

AH (mechanical; complete zona breach; ? hours egg retrieval to AH;? hours AH to transfer) versus no AH
AH: 22 women randomised, 83 embryos transferred
control: 22 women randomised, 78 embryos transferred

Outcomes

implantation, clinical pregnancy, multiple pregnancy

Notes

No attempt to contact author about this study

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Laffoon 1999

Methods

Randomisation stated, but method unclear or incorrect. Allocation concealment unclear.
Single centre.
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as abstract.

Participants

Women from North America aged less than 40 years undergoing IVF. Mean age not stated.

Interventions

AH (mechanical; complete zona breach; ? hours egg retrieval to AH;? hours AH to transfer) versus no AH
AH: 28 women randomised, embryos transferred not stated
control: 28 women randomised, embryos transferred not stated

Outcomes

clinical pregnancy

Notes

No attempt to contact author about this study

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Lanzendorf 1998

Methods

Randomised, method stated. Allocation concealment unclear.
Single centre.
Participants blinded.
Assessor blinded.
Unclear if power calculation performed.
ITT analysis performed.
Published as full paper.

Participants

Women from North America aged at least 36 years (mean basal FSH control 7.6 IU/l (sd 2.0), AH 7.9 IU/l (sd 2.5)), undergoing IVF (some with ICSI), half had been previously treated with IVF. Mean age control 38.5 (1.8), AH 38.3 (2.0).

Interventions

AH by acid tyrodes (chemical; complete zona breach; 55 hours egg retrieval to AH;? hours AH to transfer) versus no AH
AH: 42 women randomised, 180 embryos transferred
control: 52 women randomised, 212 embryos transferred

Outcomes

implantation, clinical pregnancy, multiple pregnancy, live births

Notes

Attempted to contact author about this study. A reply including much useful additional information was received.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Mansour 2000A

Methods

Randomisation stated, but method unclear or incorrect. Allocation concealment inadequate.
Single centre.
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from Egypt less than 40 years old and undergoing their first ICSI treatment. Mean age control 33.2 (1.4), AH 32.1 (2.5).

Interventions

AH with acid tyrodes (chemical; complete zona breach; 72 hours egg retrieval to AH; 2 hours AH to transfer) versus no AH
AH: 27 women randomised, 86 embryos transferred
control: 25 women randomised, 75 embryos transferred

Outcomes

clinical pregnancy, live births, miscarriage, multiple pregnancy

Notes

No attempt to contact author about this study

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

High risk

C ‐ Inadequate

Mansour 2000B

Methods

Randomisation stated, but method unclear or incorrect. Allocation concealment inadequate.
Single centre.
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from Egypt with poor prognosis (at least 40 years old and/or with 2 previous IVF or ICSI failures) undergoing ICSI treatment. Mean age control 36.3 (5.2), AH 37.3 (5.6).

Interventions

AH with acid tyrodes (chemical; complete zona breach; 72 hours egg retrieval to AH; 2 hours AH to transfer) versus no AH
AH: 30 women randomised, 117 embryos transferred
control: 41 women randomised, 155 embryos transferred

Outcomes

clinical pregnancy, live births, miscarriage, multiple pregnancy

Notes

No attempt to contact author about this study

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

High risk

C ‐ Inadequate

Nagy 1999

Methods

Randomisation stated, but method unclear or incorrect. Allocation concealment unclear.
Single centre.
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as abstract.

Participants

Women from Italy with cryopreserved embryos undergoing IVF and ICSI. Mean age control 31.4 (3.7), AH 32.0 (4.0).

Interventions

AH (laser; complete zona breach; ? hours egg retreival to AH;? hours AH to transfer) with concomitant removal of damaged blastomeres versus no AH and no damaged blastomere removal
AH: 20 women randomised, 65 embryos transferred
control: 20 women randomised, 52 embryos transferred

Outcomes

clinical pregnancy

Notes

No attempt to contact author about this study

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Olivennes 1997

Methods

Randomised, method stated.
Allocation concealment inadequate.
Multi‐centre.
Participants not blinded.
Assessor not blinded.
Unclear if power calculation performed.
ITT analysis unclear
Published as abstract.

Participants

Women from France undergoing IVF with high basal FSH (>8iU/L). Mean ages not stated.

Interventions

AH with acid tyrodes (chemical; complete zona breach; 72 hours egg retrieval to AH; <1 hour AH to transfer) versus no AH
AH: unclear women randomised, embryos transferred not stated
control: unclear women randomised, embryos transferred not stated
(AH+control = 79 W)

Outcomes

clinical pregnancy

Notes

Attempted to contact author about this study. Useful additional information received.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

High risk

C ‐ Inadequate

Ryan 1997

Methods

Randomisation stated, but method unclear or incorrect. Allocation concealment unclear.
Single centre.
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as abstract.

Participants

Women from Australia undergoing IVF with or without ICSI, with cryopreserved or fresh embryos. Mean age not stated.

Interventions

AH with acide tyrodes (chemical; complete zona breach; ? hours egg retrieval to AH; 2 hours AH to transfer) versus no AH
AH: 100 women randomised, 217 embryos transferred (estimated)
control: 100 women randomised, 217 embryos transferred (estimated)

Outcomes

pregnancy

Notes

Attempted to contact author about this study, no reply received

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Stein 1995

Methods

Randomisation stated, but method unclear or incorrect. Allocation concealment unclear.
Single centre.
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from Israel with repeated implantation failure (>3 attempts) undergoing IVF. Mean age not stated.

Interventions

AH (mechanical; complete zona breach; ? hours egg retrieval to AH; 1.5 hours AH to transfer) versus no AH
AH: 72 women randomised, 230 embryos transferred
control: 82 women randomised, 295 embryos transferred

Outcomes

clinical pregnancy, miscarriage

Notes

Attempted to contact author about this study, no reply received

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Tucker 1993

Methods

Randomisation stated, but method unclear or incorrect. Allocation concealment unclear.
Single centre.
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from North America undergoing IVF. (Mean basal FSH control 9.0 (5.3), AH 8.8 (3.7) IU/L). Mean age control 34.2 (4.1), AH 34.1 (4.8).

Interventions

AH with acid tyrodes (chemical; partial zona breach; 72 hours egg retrieval to AH; 1‐3 hours AH to transfer) versus no AH
AH: 110 women randomised, 333 embryos transferred
control: 108 women randomised, 312 embryos transferred

Outcomes

implantation, clinical pregnancy

Notes

Attempted to contact author about this study, no reply received

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Tucker 1996

Methods

Randomisation stated, but method unclear or incorrect. Allocation concealment unclear.
Single centre.
Participants not blinded or unclear.
Assessor not blinded or unclear.
Unclear if power calculation performed.
ITT analysis unclear
Published as full paper.

Participants

Women from North America undergoing ICSI. Mean age control 33.5 (4.3), AH 35.3 (4.2).

Interventions

AH with acid tyrodes (chemical; complete zona breach; 72 hours egg retrieval to AH; 4 hours AH to transfer) versus no AH
AH: 50 women randomised, 189 embryos transferred
control: 50 women randomised, 184 embryos transferred

Outcomes

implantation, clinical pregnancy

Notes

Attempted to contact author about this study, no reply received

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

AH = assisted hatching
IVF = in‐vitro fertilisation, ICSI = intracytoplasmic sperm injection
Mean age given in years (standard deviation).
note: only arms where all or no embryos transfered were treated with AH were accepted for data extraction

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Balaban 2002

Not randomised. No appropriate controls.

Bider 1997

Not randomised.

Blake 2001

Not randomised. No embryo transfer occurred, so no review outcomes could be measured.

Check 1996

Not randomised. Benefits of AH confounded by concurrent assessment of 2 different culture media.

Chen 1999

Not randomised. Benefits of assisted hatching confounded by concurrent assessment of two different culture media.

Cieslak 1999

Comparison of two types of assisted hatching, no 'no assisted hatching' control group was used. More than one cycle per woman.

Cohen 1990

Not randomised.

Dokras 1994

No appropriate outcome measure.

Domitrz 2000

Benefits of assisted hatching confounded by concurrent assessment of two different culture media.

Ebner 2002

More than one cycle per woman.

Edirisinghe 1999

Not randomised.

Hershlag 1999

Not randomised. The control group were from the period 1990‐1993, while the assisted hatching group were from 1994‐1996 (historical controls).

Huttelova 1999

Not randomised. Benefits of AH confounded by concurrent assessment of 2 different culture media.

Lee 1999

Not randomised.

Magli 1998A

More than one cycle per woman.

Magli 1998B

More than one cycle per woman.

Magli 1998C

More than one cycle per woman.

Mahadevan 1998

Not randomised. No concurrent controls.

Meldrum 1998

Not randomised. No concurrent controls.

Montag 1999

Not randomised. No concurrent controls.

Nakayama 1998

No appropriate outcome measure.

Nakayama 1999

More than one cycle per woman. Included women had treatment during one or more cycles, and it was not possible to determine events per woman (only events per cycle)

Obruca 1994

Not randomised. No concurrent controls.

Ringler 1999

It was not clear how many women were included in the study, or for how many cycles (only cycles were mentioned), and a mixture of participants and donated eggs were used for the study.

Schoolcraft 1994

Not randomised. Control and intervention groups recruited at different times.

Szell 1998

Not randomised. Benefits of assisted hatching confounded by concurrent assessment of two different culture media.

Tao 1997

Not randomised. Some of the women in the assisted hatching group were randomised, but most were allocated assisted hatching routinely, with no control option.

Tucker 1991

Not randomised.

Utsunomiya 1998

Study definition of clinical pregnancy was 'viewing of the gestational sac using ultrasound tomography', as distinct from the review definition 'foetal heartbeat on ultrasound scan', so outcome data could not be used.

Zech 1998

Numbers in tables do not add up correctly and the text and tables are contradictory on the age groups used in the prospective part of the study.

Characteristics of ongoing studies [ordered by study ID]

Germond 1998

Trial name or title

Methods

Participants

Group I, women who initiate their first transfer cycle of frozen‐thawed embryos.
Group III, selected group of women with poor prognosis of conception following transfer of fresh embryos (basal FSH >10IU/L and/or age >37 years).
Multi‐centre study across four European IVF centres, 600 women.

Interventions

Assisted hatching with a diode laser (use of immunosuppressive and antibiotic treatment will also be tested).

Outcomes

Clinical pregnancy.

Starting date

Underway in 1998.

Contact information

M. Germond, Reproductive Medicine Unit, Dept. of Obstetrics‐Gynaecology, CHUV, CH‐1011 Lausanne, Switzerland.

Notes

Data and analyses

Open in table viewer
Comparison 1. live births

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 per woman randomised, following this set of cycles Show forest plot

23

523

Odds Ratio (M‐H, Random, 95% CI)

1.21 [0.82, 1.78]

Analysis 1.1

Comparison 1 live births, Outcome 1 per woman randomised, following this set of cycles.

Comparison 1 live births, Outcome 1 per woman randomised, following this set of cycles.

2 per clinical pregnancy, following from this set of cycles Show forest plot

22

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 1.2

Comparison 1 live births, Outcome 2 per clinical pregnancy, following from this set of cycles.

Comparison 1 live births, Outcome 2 per clinical pregnancy, following from this set of cycles.

Open in table viewer
Comparison 2. clinical pregnancy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 rate per woman randomised Show forest plot

19

2175

Odds Ratio (M‐H, Random, 95% CI)

1.63 [1.27, 2.09]

Analysis 2.1

Comparison 2 clinical pregnancy, Outcome 1 rate per woman randomised.

Comparison 2 clinical pregnancy, Outcome 1 rate per woman randomised.

2 Subgrouping according to first or repeat IVF attempt Show forest plot

8

Odds Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 2.2

Comparison 2 clinical pregnancy, Outcome 2 Subgrouping according to first or repeat IVF attempt.

Comparison 2 clinical pregnancy, Outcome 2 Subgrouping according to first or repeat IVF attempt.

2.1 First attempt at IVF or ICSI

4

586

Odds Ratio (M‐H, Random, 95% CI)

1.40 [0.77, 2.53]

2.2 Repeat attempt at IVF or ICSI

4

666

Odds Ratio (M‐H, Random, 95% CI)

2.33 [1.63, 3.34]

Open in table viewer
Comparison 3. miscarriages

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 per clinical pregnancy Show forest plot

11

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 3.1

Comparison 3 miscarriages, Outcome 1 per clinical pregnancy.

Comparison 3 miscarriages, Outcome 1 per clinical pregnancy.

Comparison 1 live births, Outcome 1 per woman randomised, following this set of cycles.
Figuras y tablas -
Analysis 1.1

Comparison 1 live births, Outcome 1 per woman randomised, following this set of cycles.

Comparison 1 live births, Outcome 2 per clinical pregnancy, following from this set of cycles.
Figuras y tablas -
Analysis 1.2

Comparison 1 live births, Outcome 2 per clinical pregnancy, following from this set of cycles.

Comparison 2 clinical pregnancy, Outcome 1 rate per woman randomised.
Figuras y tablas -
Analysis 2.1

Comparison 2 clinical pregnancy, Outcome 1 rate per woman randomised.

Comparison 2 clinical pregnancy, Outcome 2 Subgrouping according to first or repeat IVF attempt.
Figuras y tablas -
Analysis 2.2

Comparison 2 clinical pregnancy, Outcome 2 Subgrouping according to first or repeat IVF attempt.

Comparison 3 miscarriages, Outcome 1 per clinical pregnancy.
Figuras y tablas -
Analysis 3.1

Comparison 3 miscarriages, Outcome 1 per clinical pregnancy.

Table 1. Mean age of participants in assisted hatching and control groups

Study

n, mean age (sd) AH

n, mean age (sd) con

WMD (95% CI)

Antinori 1996A

104, 34.60 (5.20)

104, 34.80 (5.10)

‐0.20 (‐1.60 to 1.20)

Antinori 1996B

104, 34.40 (5.10)

121, 34.60 (5.20)

‐0.20 (‐1.55 to 1.15)

Antinori 1996C

72, 38.2 (1.32)

98, 37.80 (1.48)

0.40 (‐0.02 to 0.82)

Baruffi 2000

51, 31.80 (3.60)

52, 31.40 (3.60)

0.40 (‐0.99 to 1.79)

Chao 1997

33, 36.50 (5.20)

31, 34.00 (3.90)

2.50 (0.26 TO 4.74)

Cohen 1992A

39, 36.50 (3.30)

68, 36.70 (3.70)

‐0.20 (‐1.37 to 0.97)

Hellebaut 1996

60, 30.90 (4.30)

60, 30.80 (3.90)

0.10 (‐1.37 to 1.57)

Hurst 1998

13, 30.00 (0.90)

7, 30.00 (0.80)

0.00 (‐0.77 to 0.77)

Isik 2000

24, 30.50 (5.20)

22, 29.10 (3.60)

1.40 (‐1.17 to 3.97)

Lanzendorf 1998

41, 38.30 (0.31)

48, 38.50 (0.26)

‐0.20 (‐0.32 to ‐0.08)

Mansour 2000A

27, 32.10 (2.50)

25, 33.20 (1.40)

‐1.10 (‐2.19 to ‐0.01)

Mansour 2000B

30, 37.30 (5.60)

41, 36.30 (5.20)

1.00 (‐1.56 to 3.56)

Nagy 1999

20, 32.00 (4.00)

20, 31.40 (3.70)

0.60 (‐1.79 to 2.99)

Tucker 1993

110, 34.10 (4.80)

108, 34.20 (4.10)

‐0.10 (‐1.28 to 1.08)

Tucker 1996

50, 35.30 (4.20)

50, 33.50 (4.30)

1.80 (0.13 to 3.47)

Figuras y tablas -
Table 1. Mean age of participants in assisted hatching and control groups
Table 2. Meta‐analysis, subgrouping and sensitivity analysis results

Outcome

Analysis type

Description

No. of studies

OR (random effects)

95% CI

heterogeneity p

Live births, per woman randomised

Overall meta‐analysis

6

1.21

1.82 to 1.78

0.43

Live births, per woman randomised

Sensitivity analysis

Allocation concealment

0

Live births, per woman randomised

Sensitivity analysis

Method of randomisation

4

1.13

0.72 to 1.76

0.37

Live births, per woman randomised

Sensitivity analysis

Unbalanced or unreported age

4

1.31

0.71 to 2.43

0.23

Clinical pregnancy, per woman randomised

Overall meta‐analysis

19

1.63

1.27 to 2.09

0.05

Clinical pregnancy, per woman randomised

Sensitivity analysis

Allocation concealment

0

Clinical pregnancy, per woman randomised

Sensitivity analysis

Method of randomisation

7

1.34

0.79 to 2.26

0.03

Clinical pregnancy, per woman randomised

Sensitivity analysis

Unbalanced or unreported age

10

1.81

1.23 to 2.66

0.02

Clinical pregnancy, per woman randomised

Sub‐grouping

First IVF attempt

4

1.40

0.77 to 2.53

0.05

Clinical pregnancy, per woman randomised

Sub‐grouping

Repeat IVF attempt

4

2.33

1.63 to 3.34

0.51

Implantations, per woman randomised

Overall meta‐analysis

15

1.97 (incorrect, several implantations may be counted per woman)

1.28 to 3.03

<0.01

Implantations, per woman randomised

Sensitivity analysis

Allocation concealment

0

Implantations, per woman randomised

Sensitivity analysis

Method of randomisation

9

2.10 (incorrect, several implantations may be counted per woman)

1.12 to 3.92

<0.01

Implantations, per woman randomised

Sensitivity analysis

Unbalanced or unreported age

10

2.11 (incorrect, several implantations may be counted per woman)

1.35 to 3.28

<0.01

Implantations, per embryo transferred

Overall meta‐analysis

15

1.52 (incorrect, several implantations may be counted per woman)

1.16 to 2.00 (incorrect, real 95% CI would be wider)!!

<0.01

Miscarriage, per clinical pregnancy

Overall meta‐analysis

11

0.70

0.41 to 1.19 (may be too wide as clinical pregnancies fewer than women randomised)

0.91

Live births, per clinical pregnancy

Overall meta‐analysis

6

1.07

0.46 to 2.52 (may be too wide as clinical pregnancies fewer than women randomised)

0.74

Mean age in AH and control groups

Overall meta‐analysis

15

WMD = 0.09 years

‐0.24 to 0.43

0.05

Figuras y tablas -
Table 2. Meta‐analysis, subgrouping and sensitivity analysis results
Table 3. Metaregression results, effect of assisted hatching on clinical pregnancy

analysis

explanatory variable

slope coefficient

95% CI

p‐value for slope

no. of trials

overall meta‐regression

mean maternal age in intervention group

0.053

‐0.0004 to 0.1054

0.052

19 (some of these are subgroups from within trials)

sensitivity analysis removing age‐unbalanced studies

mean maternal age in intervention group

0.097

‐0.0025 to 0.1970

0.056

10 (some of these are subgroups from within trials)

sensitivity analysis removing studies where randomisation method unclear

mean maternal age in intervention group

0.068

‐0.0168 to 0.1520

0.116

7 (some of these are subgroups from within trials)

Figuras y tablas -
Table 3. Metaregression results, effect of assisted hatching on clinical pregnancy
Table 4. Implantation data

Study

implantations, AH

women rand., AH

embryos trans., AH

imlant., control

women rand., cont.

embryos trans., cont

Antinori 1996A

46

96

376

28

104

381

Antinori 1996B

47

111

397

29

121

411

Antinori 1996C

35

72

218

21

98

407

Baruffi 2000

25

51

141

31

52

149

Chao 1997

17

33

155

5

31

1134

Cohen 1992A

67

69

239

49

68

229

Cohen 1992B

10

15

38

4

15

41

Hellebaut 1996

30

60

168

28

60

162

Hurst 1998

5

13

52

3

7

28

Isik 2000

17

24

71

12

22

63

Isiklar 1999

32

83

13

78

Lanzendorf 1998

20

41

183

24

48

219

Nagy 1999

11

20

65

2

20

52

Tucker 1993

73

110

333

59

108

312

Tucker 1996

16

50

189

25

50

184

Figuras y tablas -
Table 4. Implantation data
Comparison 1. live births

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 per woman randomised, following this set of cycles Show forest plot

23

523

Odds Ratio (M‐H, Random, 95% CI)

1.21 [0.82, 1.78]

2 per clinical pregnancy, following from this set of cycles Show forest plot

22

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Figuras y tablas -
Comparison 1. live births
Comparison 2. clinical pregnancy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 rate per woman randomised Show forest plot

19

2175

Odds Ratio (M‐H, Random, 95% CI)

1.63 [1.27, 2.09]

2 Subgrouping according to first or repeat IVF attempt Show forest plot

8

Odds Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 First attempt at IVF or ICSI

4

586

Odds Ratio (M‐H, Random, 95% CI)

1.40 [0.77, 2.53]

2.2 Repeat attempt at IVF or ICSI

4

666

Odds Ratio (M‐H, Random, 95% CI)

2.33 [1.63, 3.34]

Figuras y tablas -
Comparison 2. clinical pregnancy
Comparison 3. miscarriages

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 per clinical pregnancy Show forest plot

11

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Figuras y tablas -
Comparison 3. miscarriages