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Meta-Analysis
. 2012 Dec 12;12(12):CD001894.
doi: 10.1002/14651858.CD001894.pub5.

Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI)

Sarah-Kate Carney  1 , Sangeeta Das, Debbie Blake, Cindy Farquhar, Mourad M W Seif, Linsey Nelson
Affiliations
Meta-Analysis

Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI)

Sarah-Kate Carney et al. Cochrane Database Syst Rev. .

Abstract

Background: Failure of implantation and conception may result from an inability of the blastocyst to escape from its outer coat, which is known as the zona pellucida. Artificial disruption of this coat is known as assisted hatching and has been proposed as a method for improving the success of assisted conception by facilitating embryo implantation.

Objectives: To determine the effect of assisted hatching (AH) of embryos from assisted conception on live birth and multiple pregnancy rates.

Search methods: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (August 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (August 2012), MEDLINE (1966 to August 2012) and EMBASE (1980 to August 2012).

Selection criteria: Three authors identified and independently screened trials. We included randomised controlled trials (RCTs) of AH (mechanical, chemical or laser disruption of the zona pellucida prior to embryo replacement) versus no AH that reported live birth or clinical pregnancy.

Data collection and analysis: Three authors independently performed quality assessments and data extraction.

Main results: Thirty-one trials reported clinical pregnancy data, including 1992 clinical pregnancies in 5728 women. There was no significant difference in the odds of live birth in the AH group compared with the control group (9 RCTs; odds ratio (OR) 1.03, 95% confidence interval (CI) 0.85 to 1.26, moderate quality evidence), with no evidence of significant heterogeneity (P = 0.38) or inconsistency (I(2) = 6%). Analysis of the clinical pregnancy rates from the nine studies which reported live birth showed a non-significant result (OR 1.03, 95% CI 0.85 to 1.25 ).Analysis of all of the studies included in this update (31 RCTs) showed that the clinical pregnancy rate in women who underwent AH was slightly improved, but the level only just reached statistical significance (OR 1.13, 95% CI 1.01 to 1.27, moderate quality evidence). However, it is important to note that the heterogeneity for this combined analysis for clinical pregnancy rate was statistically significant (P = 0.001) and the I(2) was 49%. Subgroup analysis of women who had had a previous failed attempt at IVF found improved clinical pregnancy rates in the women undergoing AH compared with the women in the control group (9 RCTs, n = 1365; OR 1.42, 95% CI 1.11 to 1.81) with I(2) = 20%. Miscarriage rates per woman were similar in both groups (14 RCTs; OR 1.03, 95% CI 0.69 to 1.54, P = 0.90, moderate quality evidence). Multiple pregnancy rates per woman were significantly increased in women who were randomised to AH compared with women in the control groups (14 RCTs, 3447 women; OR 1.38, 95% CI 1.11 to 1.70, P = 0.004, low quality evidence).

Authors' conclusions: This update has demonstrated that whilst assisted hatching (AH) does appear to offer a significantly increased chance of achieving a clinical pregnancy, the extent to which it may do so only just reaches statistical significance. The 'take home' baby rate was still not proven to be increased by AH. The included trials provided insufficient data to investigate the impact of AH on several important outcomes. Most trials still failed to report on live birth rates.

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Conflict of interest statement

None known

Figures

1
1
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
Forest plot of comparison: 1 Live birth rate, outcome: 1.1 Live birth per woman randomised.
4
4
Forest plot of comparison: 4 Multiple pregnancy rate, outcome: 4.1 Multiple pregnancy rate per woman randomised.
5
5
Forest plot of comparison: 2 Clinical pregnancy, outcome: 2.1 Clinical pregnancy rate per woman randomised.
6
6
Forest plot of comparison: 3 Miscarriage rate, outcome: 3.1 Miscarriage per woman randomised.
7
7
Forest plot of comparison: 5 Monozygotic twinning rate, outcome: 5.1 Monozygotic twinning per woman randomised.
1.1
1.1. Analysis
Comparison 1 Live birth: Assisted hatching compared with no assisted hatching, Outcome 1 Live birth per woman randomised.
1.2
1.2. Analysis
Comparison 1 Live birth: Assisted hatching compared with no assisted hatching, Outcome 2 First or repeat attempt.
1.3
1.3. Analysis
Comparison 1 Live birth: Assisted hatching compared with no assisted hatching, Outcome 3 Conception mode.
1.4
1.4. Analysis
Comparison 1 Live birth: Assisted hatching compared with no assisted hatching, Outcome 4 Hatching method.
1.5
1.5. Analysis
Comparison 1 Live birth: Assisted hatching compared with no assisted hatching, Outcome 5 Prognosis.
2.1
2.1. Analysis
Comparison 2 Multiple pregnancy: Assisted hatching compared with no assisted hatching, Outcome 1 Multiple pregnancy rate per woman randomised.
2.2
2.2. Analysis
Comparison 2 Multiple pregnancy: Assisted hatching compared with no assisted hatching, Outcome 2 First or repeat attempt.
2.3
2.3. Analysis
Comparison 2 Multiple pregnancy: Assisted hatching compared with no assisted hatching, Outcome 3 Conception mode.
2.4
2.4. Analysis
Comparison 2 Multiple pregnancy: Assisted hatching compared with no assisted hatching, Outcome 4 Hatching method.
2.5
2.5. Analysis
Comparison 2 Multiple pregnancy: Assisted hatching compared with no assisted hatching, Outcome 5 Prognosis.
2.6
2.6. Analysis
Comparison 2 Multiple pregnancy: Assisted hatching compared with no assisted hatching, Outcome 6 Multiple pregnancy rate per woman grouped by extent of assisted hatching.
2.7
2.7. Analysis
Comparison 2 Multiple pregnancy: Assisted hatching compared with no assisted hatching, Outcome 7 Multiple pregnancy per pregnancy.
3.1
3.1. Analysis
Comparison 3 Clinical pregnancy: Assisted hatching compared with no assisted hatching, Outcome 1 Clinical pregnancy rate per woman randomised.
3.2
3.2. Analysis
Comparison 3 Clinical pregnancy: Assisted hatching compared with no assisted hatching, Outcome 2 First or repeat attempt.
3.3
3.3. Analysis
Comparison 3 Clinical pregnancy: Assisted hatching compared with no assisted hatching, Outcome 3 Conception mode.
3.4
3.4. Analysis
Comparison 3 Clinical pregnancy: Assisted hatching compared with no assisted hatching, Outcome 4 Hatching method.
3.5
3.5. Analysis
Comparison 3 Clinical pregnancy: Assisted hatching compared with no assisted hatching, Outcome 5 Prognosis.
3.6
3.6. Analysis
Comparison 3 Clinical pregnancy: Assisted hatching compared with no assisted hatching, Outcome 6 Extent of assisted hatching.
3.7
3.7. Analysis
Comparison 3 Clinical pregnancy: Assisted hatching compared with no assisted hatching, Outcome 7 Fresh and frozen embryo transfer.
4.1
4.1. Analysis
Comparison 4 Clinical pregnancies in trials which reported live births: Assisted hatching compared with no assisted hatching, Outcome 1 Clinical Pregnancies in trials reporting live births.
5.1
5.1. Analysis
Comparison 5 Miscarriage: Assisted hatching compared with no assisted hatching, Outcome 1 Miscarriage per woman randomised.
5.2
5.2. Analysis
Comparison 5 Miscarriage: Assisted hatching compared with no assisted hatching, Outcome 2 First or repeat attempt.
5.3
5.3. Analysis
Comparison 5 Miscarriage: Assisted hatching compared with no assisted hatching, Outcome 3 Conception mode.
5.4
5.4. Analysis
Comparison 5 Miscarriage: Assisted hatching compared with no assisted hatching, Outcome 4 Hatching method.
5.5
5.5. Analysis
Comparison 5 Miscarriage: Assisted hatching compared with no assisted hatching, Outcome 5 Prognosis.
5.6
5.6. Analysis
Comparison 5 Miscarriage: Assisted hatching compared with no assisted hatching, Outcome 6 Miscarriage per clinical pregnancy.
6.1
6.1. Analysis
Comparison 6 Monozygotic twinning: Assisted hatching compared with no assisted hatching, Outcome 1 Monozygotic twinning per woman randomised.
7.1
7.1. Analysis
Comparison 7 Robust studies (randomisation method and allocation concealment stated & live birth reported): Assisted hatching compared with no assisted hatching, Outcome 1 Live Births.
7.2
7.2. Analysis
Comparison 7 Robust studies (randomisation method and allocation concealment stated & live birth reported): Assisted hatching compared with no assisted hatching, Outcome 2 Clinical Pregnancies.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Antinori 1999 {published data only}
    1. Antinori S, Versaci C, Dani L, Barbaro E, Antinori M, Cerusico C, et al. 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.
Balaban 2006 {published data only}
    1. Balaban B, Urman B, Yakin K, Isiklar A. Laser assisted hatching increases pregnancy and implantation rates in cryopreserved embryos that were allowed to cleave in‐vitro after thawing: a prospective randomised study. Human Reproduction; 2006;21(8):2136‐40. - PubMed
Balakier 2009 {published data only}
    1. Balakier H, Mandel R, Sojecki A, Motamedi G, Zaver S, Librach C. Laser zona thinning in women aged < or = 37 years: a randomized study. Fertility and Sterility 2009;91(4 Suppl):1479‐82. [PUBMED: 18793768] - PubMed
Baruffi 2000 {published data only}
    1. 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. - PMC - PubMed
Carter 2003 {published and unpublished data}
    1. Carter J, Graham J, Han T, Davis A, Richter K, Widra E. Preliminary results of a prospective randomized study to assess the value of laser assisted hatching before cleavage stage embryo transfer among good‐prognosis in vitro fertilization (IVF) patients. Fertility and Sterility 2003;80 Suppl 3:S94.
Ciray 2005 {published data only}
    1. Ciray HN, Bener F, Karagenc L, Ulug U, Bahceci M. Impact of assisted hatching on ART outcome in women with endometriosis. Human Reproduction 2005;20(9):2546‐9. - PubMed
Cohen 1992 {published data only}
    1. 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. - PubMed
    1. 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). - PubMed
    1. Liu H‐C, Cohen J, Alikani M, Noyes N, Rosenwaks Z. Assisted hatching facilitates earlier implantation. Fertility and Sterility 1993;60(5):871‐5. - PubMed
Elhelw 2005 {published data only}
    1. Elhelw B, Sadek MM, Al Nomrosy KM. Laser assisted hatching may enhance implantation and pregnancy rates on cryopreserved‐thawed embryos in patients with repeated implantation failures. A prospective randomised study. ESHRE Copenhagen ‐ poster abstract. 2005.
Fang 2010 {published data only}
    1. Fang C, Li T, Miao BY, Zhuang GL, Zhou C. Mechanically expanding the zona pellucida of human frozen thawed embryos: a new method of assisted hatching. Fertility and Sterility 2010;94(4):1302‐7. [PUBMED: 19782973] - PubMed
Ge 2008 {published data only}
    1. Ge HS, Zhou W, Zhang W, Lin JJ. Impact of assisted hatching on fresh and frozen‐thawed embryo transfer cycles: a prospective, randomized study. Reproductive Biomedicine Online 2008;16(4):589‐96. [PUBMED: 18413070] - PubMed
Germond 2004 {published data only}
    1. Primi M‐P, Senn A, Montag M, Ven H, Mandelbaum J, Veiga A, et al. A European multicentre prospective randomized study to assess the use of assisted hatching with a diode laser and the benefit of immunosuppressive/antibiotic treatment in different patient populations. Human Reproduction 2004;19(10):2325‐33. - PubMed
Hagemann 2010 {published data only}
    1. Hagemann AR, Lanzendorf SE, Jungheim ES, Chang AS, Ratts VS, Odem RR. A prospective, randomized, double‐blinded study of assisted hatching in women younger than 38 years undergoing in vitro fertilization. Fertility and Sterility 2010;93(2):586‐91. [PUBMED: 19268926] - PubMed
Hellebaut 1996 {published and unpublished data}
    1. Hellebaut S, 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 and Genetics 1996;13(1):19‐22. - PubMed
Hurst 1998 {published and unpublished data}
    1. Hurst BS, Tucker KE, Awoniyi CA, Schlaff WD. Assisted hatching does not enhance IVF success in good‐prognosis patients. Journal of Assisted Reproduction and Genetics 1998;15(2):62‐4. - PMC - PubMed
Isik 2000 {published data only}
    1. 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. - PMC - PubMed
Isiklar 1999 {published data only}
    1. 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.
Jelinkova 2002 {published data only}
    1. Jelinkova L, Pavelkova J, Reeka N, Paulus W, Zivny J, Sterzik K. Chemical removal of the zona pellucida improves implantation. Human Reproduction 2002;17:131. - PubMed
    1. Jelinkova L, Pavelkova J, Strehler E, Paulus W, Zivny J, Sterzik K. Improved implantation rate after chemical removal of the zona pellucida. Fertility and Sterility 2003;79 Suppl 6:1299‐303. - PubMed
Kutlu 2010 {published data only}
    1. Pelin Kutlu, Ozhan Atwar, Omer Faruk Vanlioglu. Laser assisted zona thinning technique has no beneficial effect on the ART outcomes of two different maternal age groups. Journal of Assisted Reproduction and Genetics 2010;27(8):457‐61. - PMC - PubMed
Laffoon 1999 {published data only}
    1. 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}
    1. 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. - PubMed
Nagy 1999 {published data only}
    1. 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.
Ng 2005 {published data only}
    1. Ng EHY, Naveed F, Lau EYL, Yeung WSB, Chan CCWC, Tang OS, et al. A randomized double‐blind controlled study of the efficacy of laser‐assisted hatching on implantation and pregnancy rates of frozen‐thawed embryo transfer at the cleavage stage. Human Reproduction 2005;20:979‐85. - PubMed
Petersen 2005 {published data only}
    1. Petersen CG, Mauri AL, Baruffi RL, Oliveira JBA, Massaro FC, Elder K, et al. Implantation failures: success of assisted hatching with quarter‐laser zona thinning. Reproductive Biomedicine Online 2005;10 Suppl 2:224‐9. - PubMed
Rufas‐Sapir 2004 {published data only}
    1. Rufas‐Sapir O, Stein A, Orvieto R, Avrech OM, Kotler N, Pinkas H, et al. Is assisted hatching beneficial in patients with recurrent implantation failures. Clinical & Experimental Obstetrics & Gynecology 2004;31 Suppl 2:110‐2. - PubMed
Ryan 1997 {published data only}
    1. 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.
Sagoskin 2007 {published data only}
    1. Sagoskin AW, Levy MJ, Tucker MJ, Richter KS, Widra EA. Laser assisted hatching in good prognosis patients undergoing in vitro fertilisation embryo transfer: a randomised control trial. Fertility and Sterility 2007;87(2):283‐7. - PubMed
Stein 1995 {published data only}
    1. 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 and Sterility 1995;63(4):838‐41. - PubMed
Tucker 1993 {published data only}
    1. 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 and Genetics 1993;10(3):187‐91. - PubMed
Tucker 1996 {published data only}
    1. 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. - PubMed
Utsunomiya 1998 {published data only}
    1. 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.
Valojerdi 2010 {published data only}
    1. Valojerdi MR, Eftekhari‐Yazdi P, Karimian L, Hassani F, Movaghar B. Effect of laser zona thinning on vitrified‐warmed embryo transfer at the cleavage stage: a prospective, randomized study. Reproductive Biomedicine Online 2010;20(2):234‐42. [PUBMED: 20113961] - PubMed

References to studies excluded from this review

Abdelmassih 2002 {published data only}
    1. Abdelmassih S, Cardoso J, Abdelmassih V, Dias JA, Abdelmassih R, Nagy ZP. Laser‐assisted ICSI: a novel approach to obtain higher oocyte survival and embryo quality rates. Human Reproduction 2002;17 Suppl 10:2694‐7. - PubMed
Antinori 1996a {published data only}
    1. Antinori S, Selman HA, Caffa B, Panci C, Dani G, 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;11:2488‐92. - PubMed
Antinori 1996b {published data only}
    1. 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;11:590‐4. - PubMed
Balaban 2002 {published data only}
    1. 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. - PubMed
Bider 1997 {published data only}
    1. 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. - PubMed
Blake 2001 {published data only}
    1. 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. - PubMed
Carter 2003a {published data only}
    1. Carter J, Graham J, Han T, Davis A, Richter K, Widra E. Preliminary results of a prospective randomized study to assess the value of laser assisted hatching before cleavage stage embryo transfer among good‐prognosis In Vitro Fertilization (IVF) patients. Fertility and Sterility 2003;80 Suppl 3:S94.
Chao 1997 {published data only}
    1. 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 and Sterility 1997;67:904‐8. - PubMed
Check 1996 {published data only}
    1. Check JH, Hoover L, Nazari A, O'Shaughnessy A, Summers D. The effect of assisted hatching on pregnancy rates after frozen embryo transfer. Fertility and Sterility 1996;65:254‐7. - PubMed
Chen 1999 {published data only}
    1. 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 and Human Reproductive Genetics, Bologna, Italy. Monduzzi, 1999:169‐72.
Cieslak 1999 {published data only}
    1. 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. - PubMed
Cohen 1990 {published data only}
    1. 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. - PubMed
Debrock 2011 {published data only}
    1. Debrock D, Peeraer K, Spiessens C, Willeman D, Loecker P, D'Hooghe TM. The effect of modified quarter laser‐assisted zona hardening on the implantation rate per embryo in frozen/vitrified‐thawed/warmed embryo transfer cycles: a prospective randomized controlled trial. Human Reproduction June 2011;26:1997‐2007. - PubMed
Demirol 2003 {published data only}
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Dirnfeld 2003 {published data only}
    1. Dirnfeld M, Shiloh H, Bider D, Harari E, Koifman M, Lahav Baratz S, et al. A prospective randomized controlled study of the effect of short coincubation of gametes during insemination on zona pellucida thickness. Gynecological Endocrinology 2003;17:397‐403. - PubMed
Dokras 1994 {published data only}
    1. Dokras A, Ross C, Gosden B, Sargent IL, Barlow DH. Micromanipulation of human embryos to assist hatching. Fertility and Sterility 1994;61:514‐20. - PubMed
Domitrz 2000 {published data only}
    1. 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. Ginekologia Polska 2000;71:1047‐52. - PubMed
Ebner 2002 {published data only}
    1. 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. - PubMed
Edirisinghe 1999 {published data only}
    1. 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 and Genetics 1999;16:294‐301. - PMC - PubMed
Feng 2009 {published data only}
    1. Feng HL, Hershlag A, Scholl GM, Cohen MA. A retroprospective study comparing three different assisted hatching techniques. Fertility and sterility 2009;91(4 Suppl):1323‐5. [PUBMED: 18394610] - PubMed
Figueira 2012 {published data only}
    1. Figueira R, Paes D, Setti A, Iaconelli A, Borges E. Relevance of assisted hatching in an oocyte donation programme using egg cryobanking: a prospective randomised study. European Journal of Obstetrics, Gynecology, and Reproductive Biology May 2012;164:48‐51. - PubMed
Frydman 2006 {published data only}
    1. Frydman N, Madoux S, Hesters L, Duvernoy C, Feyereisen E, Du A, et al. A randomised double‐blind controlled study on the efficacy of laser zona pellucida thinning on live birth rates in cases of advanced female age. Human Reproduction 2006;21(8):2131‐5. - PubMed
Gabrielsen 2004 {published data only}
    1. Gabrielsen A, Agerholm I, Toft B, Hald F, Petersen K, Aagaard J, et al. Assisted hatching improves implantation rates on cryopreserved‐thawed embryos: a randomized prospective study. Human Reproduction 2004;19:2258‐62. - PubMed
Grace 2007 {published data only}
    1. Grace J, Bolton V, Braude P, Khalaf Y. Assisted hatching is more effective when embryo quality was optimal in previous failed IVF/ICSI cycles. Journal of Obstetrics and Gynaecology 2007;27(1):56‐60. [PUBMED: 17365461] - PubMed
Hershlag 1999 {published data only}
    1. 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. - PubMed
Hiraoka 2009 {published data only}
    1. Hiraoka K, Hiraoka K, Horiuchi T, Kusuda T, Okano S, Kinutani M, et al. Impact of the size of zona pellucida thinning area on vitrified‐warmed cleavage‐stage embryo transfers: a prospective, randomized study. Journal of Assisted Reproduction and Genetics 2009;26(9‐10):515‐21. [PUBMED: 19830543] - PMC - PubMed
Hur 2011 {published data only}
    1. Hur YS, Park JH, Ryu EY, Yoon HJ, Yoon SH, Hur CY, et al. Effect of artificial shrinkage on outcome in fresh blastocyst transfer cycles. Clinical and Experimental Reproductive Medicine 2011;38(2):87‐92. - PMC - PubMed
Huttelova 1999 {published data only}
    1. 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.
Komarovsky 2002 {published data only}
    1. Komarovsky D, Strassburger D, Raziel A, Kasterstein E, Schachter M, Friedler S, et al. A prospective randomized trial of assisted hatching in cryopreserved embryo transfer. Human Reproduction 2002;17:76.
Komarovsky 2003 {published data only}
    1. Komarovsky D, Bern O, Kasterstein E, Strassburger D, Raziel A, Friedler S, et al. A prospective randomized comparison between laser and chemically‐assisted hatching in thawed embryo transfers. Human Reproduction 2003;18 Suppl 1:77.
Lee 1999 {published data only}
    1. Lee JE, Lee DR, Paik HR, Shim HN, Cho JH, Roh SI, et al. 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.
Levron 2003 {published data only}
    1. Levron J, Ferber Meiri B, Bider D, Shulman A, Levin T, Shporn E. A prospective randomized study comparing laser and tyrode's medicated methods of assisted hatching. Fertility and Sterility 2003;80 Suppl 3:S202.
Ma 2007 {published data only}
    1. Ma S, Rowe T, Ho Yuen B. Impact of assisted hatching on the outcome of intracytoplasmic sperm injection: a prospective, randomized clinical trial and pregnancy follow‐up. Fertility and Sterility 2006;85(4):895‐900. - PubMed
Magli 1998 {published and unpublished data}
    1. 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. - PubMed
Mahadevan 1998 {published data only}
    1. Mahadevan MM, Miller MM, Maris MO, Moutos D. Assisted hatching of embryos by micromanipulation for human in vitro fertilization: UAMS experience. Journal of the Arkansas Medical Society 1998;94:529‐31. - PubMed
Mansour 2000 {published data only}
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Meldrum 1998 {published data only}
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