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Cochrane Database of Systematic Reviews

Fecundación asistida en la reproducción asistida (fecundación in vitro [FIV] e inyección intracitoplasmática de espermatozoides [ICSI])

Información

DOI:
https://doi.org/10.1002/14651858.CD001894.pub6Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 17 marzo 2021see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:
  1. Grupo Cochrane de Ginecología y fertilidad

Copyright:
  1. Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Contraer

Autores

  • Lauren Lacey

    Warwick Medical School, University of Warwick, Coventry, UK

  • Sibte Hassan

    Department of Reproductive Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK

  • Sebastian Franik

    Department of Obstetrics and Gynaecology, University Hospital Münster, Münster, Germany

  • Mourad W Seif

    Department of Gynaecology, St Mary's Hospital, Manchester, UK

  • M Ahsan Akhtar

    Correspondencia a: Reproductive Medicine, St Mary's Hospital, Manchester, UK

    [email protected]

Contributions of authors

Mourad Seif contributed to conceiving the review, designing the review, publishing the protocol, co‐ordinating the review, collecting data for the review, developing a search strategy, undertaking searches, screening search results, organising retrieval of papers, screening retrieved papers against inclusion criteria, arbitrating on quality and data extraction, interpreting data, providing a methodological perspective, providing a clinical perspective, providing a policy perspective, editing the review, providing general advice on the review, and performing previous work that was the foundation of the review.

Muhammad A Akhtar updated this review by extracting data, conducting analysis, and editing the review in detail.

Lauren Lacey updated this review by completing new searches, retrieving papers, screening retrieved papers against inclusion criteria, extracting data, conducting analysis, and editing the review in detail.

Sibte Hassan updated this review by completing new searches, retrieving papers, and screening retrieved papers against inclusion criteria.

Sebastian Franik updated this review by providing support in analysis and editing the review.

Sources of support

Internal sources

  • Central Manchester and Manchester Children's University Trust, UK

  • University of Manchester, UK

  • University of Auckland, New Zealand

External sources

  • Ministry of Health, New Zealand

  • Dr. Demián Glujovsky, Editor, Cochrane, Other

    Translated González‐Ortega et al., 2015 (published in Spanish) and extracted data from the paper for the purposes of this review.

  • Dr. Jasmine Lee, Other

    Translated Lu et al., 2016 (published in Chinese) and extracted data for the purposes of this review.

Declarations of interest

MAA, SF, SH and LL have no interests to declare.  MS has received travel and accommodation support for conferences unrelated to the topic of this review.

Acknowledgements

We wish to thank Helen Nagels and Marian Showell of the Cochrane Gynaecology and Fertility Group for help with literature searches and professional support that was invaluable to this update.

The authors of the 2020 update thank Dr. Debbie Blake and Dr. Kenneth Ma for contributions to early drafts of this update.  They also thank Dr Paraskevi Vogiatzi, Dr Annika Strandell and Professor Andy Vail for providing referee comment on the updated review. 

We wish to thank Dr. Demián Glujovsky for translating González‐Ortega et al., 2015 (published in Spanish) and for extracting data from the paper for the purposes of this review.

We wish to thank Dr. Jasmine Lee for translating Lu et al., 2016 (published in Chinese) and for extracting data for the purposes of this review.

We wish to thank Dr. Claudia González Ortega and Dr. Iman Halvaei for their correspondence to support the risk of bias assessments for their studies, González‐Ortega 2015 and Razi 2013, respectively.

We acknowledge the editorial board of the Cochrane Gynaecology and Fertility Group for support and advice provided.

We acknowledge the significant contributions of others to the original review and the updates that followed, including previous review authors, S Dias and Prof C Farquhar.

Edmond Edi‐Osagie contributed to the designing and worked on the original review.

Lee Hooper developed the second search strategy, undertook the February 2002 searches, and screened these search results, the late Phil McGinlay contributed to designing the original review, and we acknowledge the contributions of Sarah‐Kate Carney and Linsey Nelson.

Version history

Published

Title

Stage

Authors

Version

2021 Mar 17

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

Review

Lauren Lacey, Sibte Hassan, Sebastian Franik, Mourad W Seif, M Ahsan Akhtar

https://doi.org/10.1002/14651858.CD001894.pub6

2012 Dec 12

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

Review

Sarah‐Kate Carney, Sangeeta Das, Debbie Blake, Cindy Farquhar, Mourad M Seif, Linsey Nelson

https://doi.org/10.1002/14651858.CD001894.pub5

2009 Apr 15

Assisted hatching on assisted conception (IVF and ICSI)

Review

Sangeeta Das, Debbie Blake, Cindy Farquhar, Mourad MW Seif

https://doi.org/10.1002/14651858.CD001894.pub4

2006 Jan 25

Assisted hatching on assisted conception (IVF and ICSI)

Review

Sangeeta Das, Debbie Blake, Cindy Farquhar, Mourad MW Seif

https://doi.org/10.1002/14651858.CD001894.pub3

2005 Oct 19

Assisted hatching on assisted conception (IVF & ICSI)

Review

Mourad MW Seif, Edmond CO Edi‐Osagie, Cindy M Farquhar, Lee Hooper, Debbie A Blake, Phil McGinlay

https://doi.org/10.1002/14651858.CD001894.pub2

2003 Oct 20

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

Review

Edmond CO Edi‐Osagie, Lee Hooper, Phil McGinlay, Mourad MW Seif

https://doi.org/10.1002/14651858.CD001894

Differences between protocol and review

For the 2005 update, we investigated the following subgroups.

  • Age (when reported in the studies) ≥ 35 years.

  • First cycle versus previous failed cycles of IVF, ICSI, or both.

  • ICSI only cycles.

  • Chemical versus laser versus mechanical.

  • Thinning versus breach with hole versus complete removal.

For the 2007 update, the subgroup of poor prognosis women (age ≥ 35, poor ovulation induction, previous failed cycles, or referred to as poor prognosis women in the protocol) and new subgroups of fresh and frozen embryo transfer cycles were added.

No new subgroups were added to the 2020 update.

For the 2020 update, the review was reformatted in line with current recommended Cochrane guidance for reporting outcomes.

For the 2020 update, we added exclusion criterion: biopsied embryos were excluded (for purposes of PGS/PGD) during assisted reproduction because essentially they have largely been affected by assisted hatched with a hole made in them routinely at Day 3.

For the 2020 update, we specified which specific outcomes would be subject to sensitivity analysis. Sensitivity analysis was conducted for our primary outcomes and for clinical pregnancy, as those are the most important clinical outcomes.

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.

Figuras y tablas -
Figure 1

Study flow diagram.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Figuras y tablas -
Figure 2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Figuras y tablas -
Figure 3

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Forest plot of comparison: 1 Live birth rate, outcome: 1.1 Live birth per woman randomised.

Figuras y tablas -
Figure 4

Forest plot of comparison: 1 Live birth rate, outcome: 1.1 Live birth per woman randomised.

Funnel plot of comparison: 1 Live birth: assisted hatching compared with no assisted hatching, outcome: 1.1 Live birth per woman randomised.

Figuras y tablas -
Figure 5

Funnel plot of comparison: 1 Live birth: assisted hatching compared with no assisted hatching, outcome: 1.1 Live birth per woman randomised.

Forest plot of comparison: 4 Multiple pregnancy rate, outcome: 4.1 Multiple pregnancy rate per woman randomised.

Figuras y tablas -
Figure 6

Forest plot of comparison: 4 Multiple pregnancy rate, outcome: 4.1 Multiple pregnancy rate per woman randomised.

Forest plot of comparison: 2 Clinical pregnancy, outcome: 2.1 Clinical pregnancy rate per woman randomised.

Figuras y tablas -
Figure 7

Forest plot of comparison: 2 Clinical pregnancy, outcome: 2.1 Clinical pregnancy rate per woman randomised.

Funnel plot of comparison: 3 Clinical pregnancy: assisted hatching compared with no assisted hatching, outcome: 3.1 Clinical pregnancy rate per woman randomised.

Figuras y tablas -
Figure 8

Funnel plot of comparison: 3 Clinical pregnancy: assisted hatching compared with no assisted hatching, outcome: 3.1 Clinical pregnancy rate per woman randomised.

Funnel plot of comparison: 4 Clinical pregnancies in trials that reported live births: assisted hatching compared with no assisted hatching, outcome: 4.1 Clinical pregnancies in trials reporting live births.

Figuras y tablas -
Figure 9

Funnel plot of comparison: 4 Clinical pregnancies in trials that reported live births: assisted hatching compared with no assisted hatching, outcome: 4.1 Clinical pregnancies in trials reporting live births.

Forest plot of comparison: 3 Miscarriage rate, outcome: 3.1 Miscarriage per woman randomised.

Figuras y tablas -
Figure 10

Forest plot of comparison: 3 Miscarriage rate, outcome: 3.1 Miscarriage per woman randomised.

Forest plot of comparison: 5 Monozygotic twinning rate, outcome: 5.1 Monozygotic twinning per woman randomised.

Figuras y tablas -
Figure 11

Forest plot of comparison: 5 Monozygotic twinning rate, outcome: 5.1 Monozygotic twinning per woman randomised.

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 1: Live birth per woman randomised

Figuras y tablas -
Analysis 1.1

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 1: Live birth per woman randomised

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 2: First or repeat attempt

Figuras y tablas -
Analysis 1.2

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 2: First or repeat attempt

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 3: Conception mode

Figuras y tablas -
Analysis 1.3

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 3: Conception mode

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 4: Hatching method

Figuras y tablas -
Analysis 1.4

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 4: Hatching method

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 5: Prognosis

Figuras y tablas -
Analysis 1.5

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 5: Prognosis

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 6: Live birth rate by extent of assisted hatching

Figuras y tablas -
Analysis 1.6

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 6: Live birth rate by extent of assisted hatching

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 7: Fresh or frozen embryo transfer

Figuras y tablas -
Analysis 1.7

Comparison 1: Live birth: assisted hatching compared with no assisted hatching, Outcome 7: Fresh or frozen embryo transfer

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 1: Multiple pregnancy rate per woman randomised

Figuras y tablas -
Analysis 2.1

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 1: Multiple pregnancy rate per woman randomised

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 2: First or repeat attempt

Figuras y tablas -
Analysis 2.2

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 2: First or repeat attempt

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 3: Conception mode

Figuras y tablas -
Analysis 2.3

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 3: Conception mode

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 4: Hatching method

Figuras y tablas -
Analysis 2.4

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 4: Hatching method

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 5: Prognosis

Figuras y tablas -
Analysis 2.5

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 5: Prognosis

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 6: Multiple pregnancy rate per woman grouped by extent of assisted hatching

Figuras y tablas -
Analysis 2.6

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 6: Multiple pregnancy rate per woman grouped by extent of assisted hatching

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 7: Fresh or frozen embryo transfer

Figuras y tablas -
Analysis 2.7

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 7: Fresh or frozen embryo transfer

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 8: Multiple pregnancy per pregnancy

Figuras y tablas -
Analysis 2.8

Comparison 2: Multiple pregnancy: assisted hatching compared with no assisted hatching, Outcome 8: Multiple pregnancy per pregnancy

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 1: Clinical pregnancy rate per woman randomised

Figuras y tablas -
Analysis 3.1

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 1: Clinical pregnancy rate per woman randomised

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 2: First or repeat attempt

Figuras y tablas -
Analysis 3.2

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 2: First or repeat attempt

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 3: Conception mode

Figuras y tablas -
Analysis 3.3

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 3: Conception mode

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 4: Hatching method

Figuras y tablas -
Analysis 3.4

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 4: Hatching method

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 5: Prognosis

Figuras y tablas -
Analysis 3.5

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 5: Prognosis

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 6: Extent of assisted hatching

Figuras y tablas -
Analysis 3.6

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 6: Extent of assisted hatching

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 7: Fresh and frozen embryo transfer

Figuras y tablas -
Analysis 3.7

Comparison 3: Clinical pregnancy: assisted hatching compared with no assisted hatching, Outcome 7: Fresh and frozen embryo transfer

Comparison 4: Clinical pregnancies in trials that reported live births: assisted hatching compared with no assisted hatching, Outcome 1: Clinical pregnancies in trials reporting live births

Figuras y tablas -
Analysis 4.1

Comparison 4: Clinical pregnancies in trials that reported live births: assisted hatching compared with no assisted hatching, Outcome 1: Clinical pregnancies in trials reporting live births

Comparison 5: Miscarriage: assisted hatching compared with no assisted hatching, Outcome 1: Miscarriage per woman randomised

Figuras y tablas -
Analysis 5.1

Comparison 5: Miscarriage: assisted hatching compared with no assisted hatching, Outcome 1: Miscarriage per woman randomised

Comparison 5: Miscarriage: assisted hatching compared with no assisted hatching, Outcome 2: First or repeat attempt

Figuras y tablas -
Analysis 5.2

Comparison 5: Miscarriage: assisted hatching compared with no assisted hatching, Outcome 2: First or repeat attempt

Comparison 5: Miscarriage: assisted hatching compared with no assisted hatching, Outcome 3: Conception mode

Figuras y tablas -
Analysis 5.3

Comparison 5: Miscarriage: assisted hatching compared with no assisted hatching, Outcome 3: Conception mode

Comparison 5: Miscarriage: assisted hatching compared with no assisted hatching, Outcome 4: Hatching method

Figuras y tablas -
Analysis 5.4

Comparison 5: Miscarriage: assisted hatching compared with no assisted hatching, Outcome 4: Hatching method

Comparison 5: Miscarriage: assisted hatching compared with no assisted hatching, Outcome 5: Prognosis

Figuras y tablas -
Analysis 5.5

Comparison 5: Miscarriage: assisted hatching compared with no assisted hatching, Outcome 5: Prognosis

Comparison 5: Miscarriage: assisted hatching compared with no assisted hatching, Outcome 6: Miscarriage per clinical pregnancy

Figuras y tablas -
Analysis 5.6

Comparison 5: Miscarriage: assisted hatching compared with no assisted hatching, Outcome 6: Miscarriage per clinical pregnancy

Comparison 6: Monozygotic twinning: assisted hatching compared with no assisted hatching, Outcome 1: Monozygotic twinning per woman randomised

Figuras y tablas -
Analysis 6.1

Comparison 6: Monozygotic twinning: assisted hatching compared with no assisted hatching, Outcome 1: Monozygotic twinning per woman randomised

Comparison 7: Robust studies (randomisation method and allocation concealment stated and live birth reported): assisted hatching compared with no assisted hatching, Outcome 1: Live births

Figuras y tablas -
Analysis 7.1

Comparison 7: Robust studies (randomisation method and allocation concealment stated and live birth reported): assisted hatching compared with no assisted hatching, Outcome 1: Live births

Comparison 7: Robust studies (randomisation method and allocation concealment stated and live birth reported): assisted hatching compared with no assisted hatching, Outcome 2: Clinical pregnancies

Figuras y tablas -
Analysis 7.2

Comparison 7: Robust studies (randomisation method and allocation concealment stated and live birth reported): assisted hatching compared with no assisted hatching, Outcome 2: Clinical pregnancies

Summary of findings 1. Assisted hatching compared to no assisted hatching for women undergoing assisted conception

Assisted hatching compared to no assisted hatching for women undergoing assisted conception

Patient or population: women undergoing assisted conception

Setting: clinic
Intervention: assisted hatching
Comparison: no assisted hatching

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№. of participants
(studies)

Quality of evidence
(GRADE)

Comments

Risk with no assisted hatching

Risk with assisted hatching

Live births per woman randomised

283 per 1000

301 per 1000
(267 to 338)

OR 1.09
(0.92 to 1.29)

2849
(14 RCTs)

⊕⊕⊝⊝
LOWa

Multiple pregnancy rate per woman randomised

91 per 1000

121 per 1000
(102 to 144)

OR 1.38
(1.13 to 1.68)

4308
(18 RCTs)

⊕⊕⊝⊝
LOWb

Clinical pregnancy rate per woman randomised

322 per 1000

363 per 1000
(341 to 387)

OR 1.20
(1.09 to 1.33)

7249
(39 RCTs)

⊕⊕⊝⊝
LOWb

Miscarriage rate per woman randomised

53 per 1000

60 per 1000
(44 to 81)

OR 1.13
(0.82 to 1.56)

2810
(17 RCTs)

⊕⊝⊝⊝
VERY LOWc

*The risk in the intervention group (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; RCT: randomised controlled trial.

GRADE Working Group grades of evidence.
High quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aDowngraded two levels for serious risk of bias and publication bias: in many studies, the method was unclear and information was incomplete. The main limitation was serious risk of bias associated with poor reporting of study methods.

bDowngraded two levels for serious risk of bias and for serious inconsistency.

cDowngraded three levels for serious risk of bias, serious inconsistency, and serious imprecision (only 158 events).

Figuras y tablas -
Summary of findings 1. Assisted hatching compared to no assisted hatching for women undergoing assisted conception
Table 1. Mean age of participants in assisted hatching and control groups

Study

AH n, mean age (SD)

Control n, mean age (SD)

OR for clinical pregnancy

Abulsoud 2019

65, 39.2 (1.2)

65, 39.5 (1.2)

2.50 (1.14 to 5.49)

Antinori 1999: first IVF

73, 37.5

69, 36.0

1.27 (0.70 to 2.32)

Antinori 1999: repeat IVF

96, 27.5

103, 27

1.86 (0.81 to 4.25)

Balaban 2006

183, 32.4 (3.3)

183, 32.7 (3.1)

1.85 (1.19 to 2.86)

Balakier 2009

45, 32.5 (3.8)

39, 33.8 (3.2)

0.64 (0.27 to 1.55)

Baruffi 2000

51, 31.8 (3.6)

52, 31.4 (3.6)

0.74 (0.33 to 1.65)

Carter 2003

121, 34 (3.3)

82, 34 (3.2)

0.95 (0.54 to 1.67)

Ciray 2005

60, 33.1 (4.2)

30, 34.0 (3.7)

0.62 (0.26 to 1.49)

Cohen 1992: FSH < 15

69, 36.50 (3.30)

68, 36.70 (3.70)

2.11 (1.18 to 3.77)

Cohen 1992: poor prognosis

80, 36.7 (4.3)

83, 35.3 (4.2)

1.30 (0.66 to 2.55)

Cohen 1992: FSH > 15

not stated

not stated

1.30 (0.66 to 2.55)

Elhelw 2005

not stated

not stated

1.77 (0.52 to 6.01)

Elnahas 2017

80, 31.0 (4.7)

80, 31.7 (4.9)

1.58 (0.81 to 3.08)

Fang 2010

61, 32.3 (3.4)

64, 32.1 (3.6)

2.37 (1.07 to 5.28)

Ge 2008: fresh embryo

387, 31.08 (4.68)

373, 30.44 (4.15)

0.99 (0.74 to 1.32)

Ge 2008: frozen embryo

100, 31.84 (3.85)

100, 30.66 (4.42)

2.05 (0.99 to 4.22)

Germond 2004: first cycle of frozen‐thawed embryos

62, 32.8 (4.2)

53, 32.6 (3.8)

0.09 (0.01 to 0.76)

Germond 2004: poor prognosis, first cycle of fresh embryos

22, 39.3 (2.9)

21, 38.3 (3.4)

0.51 (0.10 to 2.45)

González‐Ortega 2015

154, 38.5 (2.8)

149, 37.3 (4.2)

2.71 (1.62 to 4.56)

Hagemann 2010

59, 32.1 (3.0)

62, 31.2 (3.5)

0.81 (0.37 to 1.76)

Hellebaut 1996

60, 30.9 (4.3)

60, 30.8 (3.9)

1.15 (0.55 to 2.43)

Hurst 1998

13, 30.0 (0.9)

7, 30.0 (0.8)

0.40 (0.06 to 2.89)

Isik 2000

24, 30.5 (5.2)

22, 29.1 (3.6)

2.0 (0.62 to 6.49)

Isiklar 1999

not stated

not stated

3.20 (0.91 to 11.27)

Jelinkova 2002

128, 32.3 (4.24)

129, 32.1 (3.16)

1.86 (1.12 to 3.10)

Kutlu 2010: good prognosis

73, 29.9 (2.9)

66, 28.9 (3.4)

1.06 (0.54 to 2.08)

Kutlu 2010: poor prognosis

58, 38.0 (2.3)

55, 37.4 (2.4)

1.23 (0.58 to 2.60)

Laffoon 1999

not stated

not stated

0.85 (0.28 to 2.58)

Lanzendorf 1998

41, 38.30 (0.31)

48, 38.50 (0.26)

0.90 (0.38 to 2.10)

Nada 2018

158, 31.3 (4.1)

150, 32.6 (2.4)

1.79 (1.05 to 3.07)

Nagy 1999

20, 32.0 (4.0)

20, 31.4 (3.7)

8.0 (1.44 to 44.3)

Ng 2005

80, 34.0 (range 25 to 40)

80, 34.0 (range 26 to 40)

0.81 (0.33 to 2.00)

Petersen 2005: 1 previous implantation failure

35, 34.6 (4.6)

35, 34.1 (5.3)

1.15 (0.41 to 3.19)

Petersen 2005: several previous implantation failures

40, 35.7 (3.8)

40, 35.3 (5.1)

4.11 (1.04 to 16.29)

Razi 2013

90, 32.9 (0.5)

92, 31.6 (0.4)

0.7 (0.3 to 1.6)

Rufas‐Sapir 2004

not stated

not stated

0.72 (0.38 to 1.36)

Ryan 1997

not stated

not stated

0.74 (0.35 to 1.59)

Safari 2017

30, 30.6 (5.6)

32, 29.2 (5.3)

0.58 (0.19 to 1.78)

Sagoskin 2007

118, 34.0 (3.3)

81, 34.0 (3.2)

0.94 (0.53 to1.65)

Shi 2016

82, 37.2 (2.22)

96, 36.97 (1.96)

0.65 (0.36 to 1.18)

Stein 1995

not stated

not stated

1.54 (0.67 to 3.54)

Tucker 1993

110, 34.1 (4.8)

108, 34.2 (4.1)

1.37 (0.79 to 2.35)

Tucker 1996

50, 35.3 (4.2)

50, 33.5 (4.3)

0.74 (0.35 to 1.59)

Utsunomiya 1998

not stated

not stated

1.36 (0.32 to 5.73)

Valojerdi 2010

200, 30.86 (5.82)

200, 29.85 (5.14)

0.53 (0.35 to 0.80)

Wan 2014

96, 33.1 (3.7)

102, 32.6 (3.4)

1.91 (1.08 to 3.38)

Figuras y tablas -
Table 1. Mean age of participants in assisted hatching and control groups
Table 2. Prognostic factors in included trials

Study ID

Balanced age between groups

Balances no. of embryos transferred

Prognosis: poor/good

FSH levels

Blastocyst transfer

Complete/partial AH

Frozen cycles

Abulsoud 2019

Yes

Yes

Poor

No data

No

Thinning

Fresh

Antinori 1999

AH mean 1.5 years older

Yes

Good and poor subgroups

No data

No

Complete hole

Not stated

Balaban 2006

Yes

Yes

Unselected

< 10

No

Thinning

Frozen

Balakier 2009

AH mean 1.3 years older

Yes

Good

< 10

No

Thinning

Fresh

Baruffi 2000

Yes

Yes

Good

No data

No

Thinning

Fresh

Carter 2003

Yes

Yes

Good

< 10

No

Not stated

Fresh

Ciray 2005

Yes

Yes

Good

< 15

No

Thinning

Fresh

Cohen 1992

Yes

Yes

Unstated

≤ 15 and > 15 subgroups

No

Complete hole

Fresh

Elhelw 2005

Yes

No data

Poor

No data

No

Thinning

Frozen

Elnahas 2017

Yes

No data

Good

No data

No

Thinning

Frozen

Fang 2010

Yes

Yes

Not stated

No data

No

Mechanical expansion

Frozen thawed

Ge 2008

Yes

Yes

Mixed

No data

No

Thinning

Fresh and frozen subgroups

Germond 2004

Yes

Yes

Mixed, in subgroups

Between 3 and 12

No

Complete hole

Fresh and frozen subgroups

González‐Ortega 2015

Yes

Yes

Poor

> 12

No

Partial

Fresh

Hagemann 2010

Mean age data given only for combined cycles 1 and 2

Yes

Under 38 years, > 2 previously failed cycles, ZP thickness > 13 micrometers

No data

No

20 micrometer diameter opening

Fresh

Hellebaut 1996

Yes

Yes

Good

No data

No

Complete hole

Fresh

Hurst 1998

Yes

Yes

Good

< 10

No

Complete hole

Fresh

Isik 2000

AH mean 1.4 years older

Yes

Unstated

< 10

Yes

Removal complete

Fresh

Isiklar 1999

No data

Yes

Unstated

No data

Yes

Complete hole

Fresh

Jelinkova 2002

Yes

Yes

Poor

No data

Yes

Removal complete

Fresh

Kutlu 2010

Yes

Yes

Good and poor subgroups

No data

No

Complete hole

Fresh

Laffoon 1999

No data

No data

Good

No data

No

Complete hole

Fresh

Lanzendorf 1998

No

Yes

Poor

No data

No

Complete hole

Fresh

Nada 2018

Yes

Yes

Good

AH 5.4 ± 1.3
No AH 6.0 ± 1.1

No

Thinning

Fresh

Nagy 1999

Yes

Yes

Unstated

No data

No

Thinning

Frozen‐thaw cycle

Ng 2005

Yes

Higher proportion of controls received 3 embryos

Unstated

< 11

No

Thinning

Frozen‐thaw cycle

Petersen 2005

Yes

Yes

Poor

No data

No

Thinning

Fresh

Razi 2013

Yes

Yes

Unstated

No data

No

Partial

Fresh

Rufas‐Sapir 2004

No data

Yes

Poor

No data

No

Complete hole

Fresh

Ryan 1997

No data

No data

Unstated

No data

No

Complete hole

Both

Safari 2017

Yes

Yes

Unstated

AH 6.4 ± 2.3

No AH 5.6 ± 2.1

No

Thinning

Frozen

Sagoskin 2007

Yes

Yes

Good

< 10

No

Hole

Fresh

Shi 2016

Yes

Yes

Advanced maternal age

< 10

No

Zona Thinning

Fresh

Stein 1995

No data

No data

Poor

No data

No

Complete hole

Fresh

Tucker 1993

Yes

Yes

Good

< 15

No

Thinning

Fresh

Tucker 1996

AH mean 1.8 years older

Yes

Not stated

No data

No

Complete hole

Fresh

Utsunomiya 1998

No data

No data

Poor

No data

No

Thinning

Fresh

Valojerdi 2010

Yes

Yes

Not stated

No data

No

Partially thinned

Vitrified‐warmed embryo

Wan 2014

Yes

Yes

Previously unsuccessful 1 fresh cycle

No data

Yes

Partial

Vitrified‐warmed embryo

AH: assisted hatching.
ET: embryo transfer.
FSH: follicle‐stimulating hormone.

Figuras y tablas -
Table 2. Prognostic factors in included trials
Comparison 1. Live birth: assisted hatching compared with no assisted hatching

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Live birth per woman randomised Show forest plot

14

2849

Odds Ratio (M‐H, Fixed, 95% CI)

1.09 [0.92, 1.29]

1.2 First or repeat attempt Show forest plot

4

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.2.1 First attempt at IVF or ICSI

3

380

Odds Ratio (M‐H, Fixed, 95% CI)

0.78 [0.48, 1.28]

1.2.2 Repeat attempt at IVF or ICSI

1

150

Odds Ratio (M‐H, Fixed, 95% CI)

1.40 [0.62, 3.13]

1.3 Conception mode Show forest plot

6

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.3.1 ICSI only

3

640

Odds Ratio (M‐H, Fixed, 95% CI)

1.54 [1.02, 2.33]

1.3.2 IVF only

3

241

Odds Ratio (M‐H, Fixed, 95% CI)

1.00 [0.60, 1.68]

1.4 Hatching method Show forest plot

14

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.4.1 Chemical

4

366

Odds Ratio (M‐H, Fixed, 95% CI)

1.13 [0.74, 1.74]

1.4.2 Laser

10

2473

Odds Ratio (M‐H, Fixed, 95% CI)

1.07 [0.89, 1.28]

1.5 Prognosis Show forest plot

9

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.5.1 Poor prognosis

4

576

Odds Ratio (M‐H, Fixed, 95% CI)

1.46 [0.99, 2.15]

1.5.2 Good prognosis

6

1495

Odds Ratio (M‐H, Fixed, 95% CI)

1.03 [0.83, 1.28]

1.6 Live birth rate by extent of assisted hatching Show forest plot

14

2849

Odds Ratio (M‐H, Fixed, 95% CI)

1.09 [0.92, 1.29]

1.6.1 Thinning only

6

1742

Odds Ratio (M‐H, Fixed, 95% CI)

1.06 [0.86, 1.30]

1.6.2 Breach by hole only

8

1107

Odds Ratio (M‐H, Fixed, 95% CI)

1.15 [0.87, 1.51]

1.7 Fresh or frozen embryo transfer Show forest plot

12

1731

Odds Ratio (M‐H, Fixed, 95% CI)

1.14 [0.92, 1.41]

1.7.1 Fresh

11

1669

Odds Ratio (M‐H, Fixed, 95% CI)

1.16 [0.94, 1.44]

1.7.2 Frozen

1

62

Odds Ratio (M‐H, Fixed, 95% CI)

0.67 [0.22, 2.07]

Figuras y tablas -
Comparison 1. Live birth: assisted hatching compared with no assisted hatching
Comparison 2. Multiple pregnancy: assisted hatching compared with no assisted hatching

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Multiple pregnancy rate per woman randomised Show forest plot

18

4308

Odds Ratio (M‐H, Fixed, 95% CI)

1.38 [1.13, 1.68]

2.2 First or repeat attempt Show forest plot

8

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.2.1 First attempt at IVF or ICSI

4

654

Odds Ratio (M‐H, Fixed, 95% CI)

0.73 [0.31, 1.72]

2.2.2 Repeat attempt at IVF or ICSI

5

1068

Odds Ratio (M‐H, Fixed, 95% CI)

1.25 [0.80, 1.94]

2.3 Conception mode Show forest plot

9

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.3.1 ICSI only

3

573

Odds Ratio (M‐H, Fixed, 95% CI)

3.09 [1.57, 6.08]

2.3.2 IVF only

6

1126

Odds Ratio (M‐H, Fixed, 95% CI)

1.87 [1.28, 2.72]

2.4 Hatching method Show forest plot

18

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.4.1 Chemical

4

534

Odds Ratio (M‐H, Fixed, 95% CI)

1.55 [0.98, 2.47]

2.4.2 Laser

13

3730

Odds Ratio (M‐H, Fixed, 95% CI)

1.29 [1.03, 1.61]

2.4.3 Mechanical

1

44

Odds Ratio (M‐H, Fixed, 95% CI)

8.33 [1.56, 44.64]

2.5 Prognosis Show forest plot

10

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.5.1 Poor prognosis

6

1186

Odds Ratio (M‐H, Fixed, 95% CI)

1.95 [1.27, 3.00]

2.5.2 Good prognosis

6

1569

Odds Ratio (M‐H, Fixed, 95% CI)

1.08 [0.81, 1.44]

2.6 Multiple pregnancy rate per woman grouped by extent of assisted hatching Show forest plot

16

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.6.1 Thinning only

6

2148

Odds Ratio (M‐H, Fixed, 95% CI)

1.34 [1.02, 1.76]

2.6.2 Breach by hole

9

1629

Odds Ratio (M‐H, Fixed, 95% CI)

1.51 [1.08, 2.11]

2.6.3 Complete removal of zona

1

25

Odds Ratio (M‐H, Fixed, 95% CI)

0.62 [0.07, 5.28]

2.7 Fresh or frozen embryo transfer Show forest plot

16

3190

Odds Ratio (M‐H, Fixed, 95% CI)

1.38 [1.08, 1.75]

2.7.1 Fresh

13

2264

Odds Ratio (M‐H, Fixed, 95% CI)

1.30 [0.98, 1.73]

2.7.2 Frozen

3

926

Odds Ratio (M‐H, Fixed, 95% CI)

1.60 [1.00, 2.55]

2.8 Multiple pregnancy per pregnancy Show forest plot

17

1598

Odds Ratio (M‐H, Fixed, 95% CI)

1.37 [1.09, 1.72]

Figuras y tablas -
Comparison 2. Multiple pregnancy: assisted hatching compared with no assisted hatching
Comparison 3. Clinical pregnancy: assisted hatching compared with no assisted hatching

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

3.1 Clinical pregnancy rate per woman randomised Show forest plot

39

7249

Odds Ratio (M‐H, Fixed, 95% CI)

1.20 [1.09, 1.33]

3.2 First or repeat attempt Show forest plot

18

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.2.1 First attempt at IVF or ICSI

8

1010

Odds Ratio (M‐H, Fixed, 95% CI)

0.74 [0.56, 0.98]

3.2.2 Repeat attempt at IVF or ICSI

11

1798

Odds Ratio (M‐H, Fixed, 95% CI)

1.65 [1.34, 2.04]

3.3 Conception mode Show forest plot

26

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.3.1 ICSI only

11

1825

Odds Ratio (M‐H, Fixed, 95% CI)

1.40 [1.14, 1.71]

3.3.2 IVF only

15

2460

Odds Ratio (M‐H, Fixed, 95% CI)

1.31 [1.10, 1.55]

3.4 Hatching method Show forest plot

39

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.4.1 Chemical

11

1536

Odds Ratio (M‐H, Fixed, 95% CI)

1.33 [1.08, 1.64]

3.4.2 Laser

23

5127

Odds Ratio (M‐H, Fixed, 95% CI)

1.15 [1.03, 1.30]

3.4.3 Mechanical

5

586

Odds Ratio (M‐H, Fixed, 95% CI)

1.30 [0.89, 1.88]

3.5 Prognosis Show forest plot

24

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.5.1 Poor prognosis

14

2108

Odds Ratio (M‐H, Fixed, 95% CI)

1.68 [1.38, 2.04]

3.5.2 Good prognosis

14

2721

Odds Ratio (M‐H, Fixed, 95% CI)

1.10 [0.94, 1.29]

3.6 Extent of assisted hatching Show forest plot

37

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.6.1 Thinning only

17

3774

Odds Ratio (M‐H, Fixed, 95% CI)

1.10 [0.96, 1.26]

3.6.2 Breach by hole only

17

2543

Odds Ratio (M‐H, Fixed, 95% CI)

1.17 [0.98, 1.39]

3.6.3 Complete removal of zona

2

301

Odds Ratio (M‐H, Fixed, 95% CI)

1.93 [1.21, 3.09]

3.6.4 Expansion of zona pellucida

1

125

Odds Ratio (M‐H, Fixed, 95% CI)

2.37 [1.07, 5.28]

3.7 Fresh and frozen embryo transfer Show forest plot

38

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.7.1 Fresh embryo transfer

30

5349

Odds Ratio (M‐H, Fixed, 95% CI)

1.23 [1.10, 1.38]

3.7.2 Frozen embryo transfer only

10

1700

Odds Ratio (M‐H, Fixed, 95% CI)

1.15 [0.93, 1.42]

Figuras y tablas -
Comparison 3. Clinical pregnancy: assisted hatching compared with no assisted hatching
Comparison 4. Clinical pregnancies in trials that reported live births: assisted hatching compared with no assisted hatching

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

4.1 Clinical pregnancies in trials reporting live births Show forest plot

14

2849

Odds Ratio (M‐H, Fixed, 95% CI)

1.07 [0.92, 1.25]

Figuras y tablas -
Comparison 4. Clinical pregnancies in trials that reported live births: assisted hatching compared with no assisted hatching
Comparison 5. Miscarriage: assisted hatching compared with no assisted hatching

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

5.1 Miscarriage per woman randomised Show forest plot

17

2810

Odds Ratio (M‐H, Fixed, 95% CI)

1.13 [0.82, 1.56]

5.2 First or repeat attempt Show forest plot

8

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.2.1 First attempt at IVF or ICSI

4

442

Odds Ratio (M‐H, Fixed, 95% CI)

0.98 [0.51, 1.89]

5.2.2 Repeat attempt at IVF or ICSI

5

966

Odds Ratio (M‐H, Fixed, 95% CI)

1.96 [0.90, 4.28]

5.3 Conception mode Show forest plot

10

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.3.1 ICSI only

4

665

Odds Ratio (M‐H, Fixed, 95% CI)

1.20 [0.58, 2.47]

5.3.2 IVF only

6

896

Odds Ratio (M‐H, Fixed, 95% CI)

1.28 [0.65, 2.52]

5.4 Hatching method Show forest plot

17

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.4.1 Chemical

5

412

Odds Ratio (M‐H, Fixed, 95% CI)

1.11 [0.56, 2.21]

5.4.2 Laser

11

2244

Odds Ratio (M‐H, Fixed, 95% CI)

1.13 [0.78, 1.64]

5.4.3 Mechanical

1

154

Odds Ratio (M‐H, Fixed, 95% CI)

1.14 [0.07, 18.58]

5.5 Prognosis Show forest plot

11

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.5.1 Poor prognosis

7

1133

Odds Ratio (M‐H, Fixed, 95% CI)

1.21 [0.70, 2.08]

5.5.2 Good prognosis

5

626

Odds Ratio (M‐H, Fixed, 95% CI)

1.03 [0.50, 2.14]

5.6 Miscarriage per clinical pregnancy Show forest plot

15

777

Odds Ratio (M‐H, Random, 95% CI)

0.94 [0.62, 1.43]

Figuras y tablas -
Comparison 5. Miscarriage: assisted hatching compared with no assisted hatching
Comparison 6. Monozygotic twinning: assisted hatching compared with no assisted hatching

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

6.1 Monozygotic twinning per woman randomised Show forest plot

6

729

Odds Ratio (M‐H, Fixed, 95% CI)

3.23 [0.34, 31.03]

Figuras y tablas -
Comparison 6. Monozygotic twinning: assisted hatching compared with no assisted hatching
Comparison 7. Robust studies (randomisation method and allocation concealment stated and live birth reported): assisted hatching compared with no assisted hatching

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

7.1 Live births Show forest plot

1

960

Odds Ratio (M‐H, Fixed, 95% CI)

1.08 [0.82, 1.41]

7.2 Clinical pregnancies Show forest plot

1

960

Odds Ratio (M‐H, Fixed, 95% CI)

1.10 [0.85, 1.43]

Figuras y tablas -
Comparison 7. Robust studies (randomisation method and allocation concealment stated and live birth reported): assisted hatching compared with no assisted hatching