Scolaris Content Display Scolaris Content Display

Cochrane Database of Systematic Reviews

Transferencia de embriones frescos versus congelados en la reproducción asistida

This is not the most recent version

Information

DOI:
https://doi.org/10.1002/14651858.CD011184.pub2Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 28 March 2017see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Gynaecology and Fertility Group

Copyright:
  1. Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Article metrics

Altmetric:

Cited by:

Cited 0 times via Crossref Cited-by Linking

Collapse

Authors

  • Kai Mee Wong

    Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

  • Madelon van Wely

    Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

  • Femke Mol

    Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

  • Sjoerd Repping

    Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

  • Sebastiaan Mastenbroek

    Correspondence to: Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

    [email protected]

Contributions of authors

Kai Mee Wong and Sebastiaan Mastenbroek wrote the review. Kai Mee Wong, Sjoerd Repping, and Sebastiaan Mastenbroek developed the concept of the study. Madelon van Wely, Femke Mol, and Sjoerd Repping provided feedback on the review.

Sources of support

Internal sources

  • None, Other.

External sources

  • None, Other.

Declarations of interest

Kai Mee Wong: none known
Madelon van Wely: none known
Femke Mol: none known
Sjoerd Repping: none known
Sebastiaan Mastenbroek is principal investigator of one of the ongoing studies.

Acknowledgements

We would like to acknowledge the team at the Cochrane Gynaecology and Fertility Group for their assistance, and especially Information Specialist Marian Showell for the literature search.

Version history

Published

Title

Stage

Authors

Version

2021 Feb 04

Fresh versus frozen embryo transfers in assisted reproduction

Review

Tjitske Zaat, Miriam Zagers, Femke Mol, Mariëtte Goddijn, Madelon Wely, Sebastiaan Mastenbroek

https://doi.org/10.1002/14651858.CD011184.pub3

2017 Mar 28

Fresh versus frozen embryo transfers in assisted reproduction

Review

Kai Mee Wong, Madelon van Wely, Femke Mol, Sjoerd Repping, Sebastiaan Mastenbroek

https://doi.org/10.1002/14651858.CD011184.pub2

2014 Jul 10

Fresh versus frozen embryo transfers for assisted reproduction

Protocol

Kai Mee Wong, Madelon van Wely, Fulco Van der Veen, Sjoerd Repping, Sebastiaan Mastenbroek

https://doi.org/10.1002/14651858.CD011184

Differences between protocol and review

We added a method of analysing time to pregnancy (by hazard ratios), as this was not reported in the protocol; in the event, no data were available for this outcome.

We performed a subgroup analysis by timing of embryo transfer for the primary outcome of cumulative live birth.

We changed the unit of analysis for birth weight (from per woman to per baby).

We added some details to the section specifying our plans for the summary of findings table.

Congenital disorders, defined as the number of congenital abnormalities at birth, were reported per live‐born children plus number of foetuses therapeutically terminated in stead of per all clinical pregnancies.

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 2

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

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 3

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

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.1 Live birth rate.
Figures and Tables -
Figure 4

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.1 Live birth rate.

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.2 OHSS.
Figures and Tables -
Figure 5

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.2 OHSS.

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.3 Ongoing pregnancy rate.
Figures and Tables -
Figure 6

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.3 Ongoing pregnancy rate.

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.4 Clinical pregnancy rate.
Figures and Tables -
Figure 7

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.4 Clinical pregnancy rate.

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.5 Multiple pregnancy rate.
Figures and Tables -
Figure 8

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.5 Multiple pregnancy rate.

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.6 Miscarriage rate.
Figures and Tables -
Figure 9

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.6 Miscarriage rate.

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.7 Pregnancy complications.
Figures and Tables -
Figure 10

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.7 Pregnancy complications.

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.8 Birth weight of babies born.
Figures and Tables -
Figure 11

Forest plot of comparison: 1 Freeze‐all vs conventional IVF, outcomes per woman, outcome: 1.8 Birth weight of babies born.

Forest plot of comparison: 3 Freeze‐all vs conventional IVF, congenital abnormalities per live‐born children plus number of foetuses therapeutically terminated, outcome: 3.1 Congenital abnormalities.
Figures and Tables -
Figure 12

Forest plot of comparison: 3 Freeze‐all vs conventional IVF, congenital abnormalities per live‐born children plus number of foetuses therapeutically terminated, outcome: 3.1 Congenital abnormalities.

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 1 Live birth rate.
Figures and Tables -
Analysis 1.1

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 1 Live birth rate.

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 2 OHSS.
Figures and Tables -
Analysis 1.2

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 2 OHSS.

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 3 Ongoing pregnancy rate.
Figures and Tables -
Analysis 1.3

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 3 Ongoing pregnancy rate.

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 4 Clinical pregnancy rate.
Figures and Tables -
Analysis 1.4

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 4 Clinical pregnancy rate.

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 5 Multiple pregnancy rate.
Figures and Tables -
Analysis 1.5

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 5 Multiple pregnancy rate.

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 6 Miscarriage rate.
Figures and Tables -
Analysis 1.6

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 6 Miscarriage rate.

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 7 Pregnancy complications.
Figures and Tables -
Analysis 1.7

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 7 Pregnancy complications.

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 8 Birth weight of babies born.
Figures and Tables -
Analysis 1.8

Comparison 1 Freeze‐all versus conventional IVF, outcomes per woman, Outcome 8 Birth weight of babies born.

Comparison 2 Freeze‐all versus conventional IVF, adverse events per clinical pregnancy, Outcome 1 Multiple pregnancy.
Figures and Tables -
Analysis 2.1

Comparison 2 Freeze‐all versus conventional IVF, adverse events per clinical pregnancy, Outcome 1 Multiple pregnancy.

Comparison 2 Freeze‐all versus conventional IVF, adverse events per clinical pregnancy, Outcome 2 Miscarriage.
Figures and Tables -
Analysis 2.2

Comparison 2 Freeze‐all versus conventional IVF, adverse events per clinical pregnancy, Outcome 2 Miscarriage.

Comparison 2 Freeze‐all versus conventional IVF, adverse events per clinical pregnancy, Outcome 3 Pregnancy complications.
Figures and Tables -
Analysis 2.3

Comparison 2 Freeze‐all versus conventional IVF, adverse events per clinical pregnancy, Outcome 3 Pregnancy complications.

Comparison 3 Freeze‐all versus conventional IVF, congenital abnormalities per live‐born children plus number of foetuses therapeutically terminated, Outcome 1 Congenital abnormalities.
Figures and Tables -
Analysis 3.1

Comparison 3 Freeze‐all versus conventional IVF, congenital abnormalities per live‐born children plus number of foetuses therapeutically terminated, Outcome 1 Congenital abnormalities.

Summary of findings for the main comparison. Fresh versus frozen embryo transfers in assisted reproduction

Fresh versus frozen embryo transfers in assisted reproduction

Patient or population: women undergoing assisted reproduction
Setting: assisted reproduction clinic
Intervention: frozen embryo transfers only
Comparison: fresh and frozen embryo transfers

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with fresh and frozen embryo transfers

Risk with frozen embryo transfers only

Live birth rate

cumulatively for all embryo stages of transfer

579 per 1000

600 per 1000
(556 to 643)

OR 1.09
(0.91 to 1.31)

1892
(4 RCTs)

⊕⊕⊕⊝
MODERATE 1

Ovarian hyperstimulation syndrome

per cycle with ovarian hyperstimulation

70 per 1000

18 per 1000
(11 to 28)

OR 0.24
(0.15 to 0.38)

1633
(2 RCTs)

⊕⊕⊝⊝
LOW 1,2

Multiple pregnancy per woman

after first ET

161 per 1000

176 per 1000

(141 to 217)

OR 1.11

(0.85 to 1.44)

1630

(2 RCTs)

⊕⊕⊝⊝
LOW 1,2

Miscarriage per woman

after first ET

184 per 1000

131 per 1000

(105 to 162)

OR 0.67

(0.52 to 0.86)

1892
(4 RCTs)

⊕⊕⊝⊝
LOW 1,2

Pregnancy complications per woman after first ET

110 per 1000

151 per 1000

(118 to 191)

OR 1.44

(1.08 to 1.92)

1633
(2 RCTs)

⊕⊕⊝⊝
LOW 1,2

Time to pregnancy

Not reported in any of the included studies

*The risk in the intervention group (and its 95% confidence interval) is based on the mean risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; ET: embryo transfer; OR: odds ratio; RCT: randomised clinical 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.

1Downgraded one level due to serious risk of bias associated with lack of power calculation (unclear what determined end of study) and/or use of interim analysis that was calculated per transfer (unit of analysis error) with absence of adequate stopping rules (possible overestimation of treatment effect).
2Downgraded one level due to serious imprecision: event rate < 300.

Figures and Tables -
Summary of findings for the main comparison. Fresh versus frozen embryo transfers in assisted reproduction
Table 1. Sensitivity analysis for cumulative live birth rate

Studies, number of participants

OR, 95% CI, fixed effect

OR, 95% CI, random effect

RR, 95% CI, fixed effect

RR, 95% CI, random effect

Ferraretti 1999 (n = 125)

Shapiro 2011a (n = 103)

Shapiro 2011b (n = 122)

Chen 2016 (n = 1508)

1.09 (0.91, 1.31)

1.09 (0.91, 1.31)

1.04 (0.96, 1.12)

1.04 (0.96, 1.12)

CI: confidence interval
OR: odds ratio
RR: risk ratio

Figures and Tables -
Table 1. Sensitivity analysis for cumulative live birth rate
Table 2. Live birth rate after first transfer

Outcome

Number of studies

Number of participants

Analysis method

OR

Live birth rate after first embryo transfer for all embryo stages of transfer

4

1892

Odds ratio (Mantel‐Haenszel, fixed, 95% confidence interval)

1.34 (1.12, 1.61)

Live birth rate after first transfer with cleavage‐stage embryos

2

1633

Odds ratio (Mantel‐Haenszel, fixed, 95% confidence interval)

1.31 (1.08, 1.59)

Live birth rate after first transfer with blastocyst‐stage embryo

2

259

Odds ratio (Mantel‐Haenszel, fixed, 95% confidence interval)

1.54 (0.94, 2.52)

Live birth rate calculated per first transfer is added for illustrative purposes as this comparison is often reported in the literature. It possibly shows differences in outcome for a stimulated and an unstimulated uterus, although this does not take into account the number of embryos that were thawed for transfer. This outcome is less relevant for women undergoing treatment since at the same time of first transfer in a freeze‐all strategy, they would already have received the second transfer (in case of sufficient number of embryos) in a conventional strategy that includes fresh transfer.

Figures and Tables -
Table 2. Live birth rate after first transfer
Comparison 1. Freeze‐all versus conventional IVF, outcomes per woman

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Live birth rate Show forest plot

4

1892

Odds Ratio (M‐H, Fixed, 95% CI)

1.09 [0.91, 1.31]

1.1 Live birth rate: cumulatively for cleavage stage transfer

2

1633

Odds Ratio (M‐H, Fixed, 95% CI)

1.11 [0.91, 1.35]

1.2 Live birth rate: cumulatively for blastocyst stage transfer

2

259

Odds Ratio (M‐H, Fixed, 95% CI)

0.99 [0.60, 1.62]

2 OHSS Show forest plot

2

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

2.1 Per cycle with ovarian hyperstimulation

2

1633

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.24 [0.15, 0.38]

3 Ongoing pregnancy rate Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Cumulatively

2

259

Odds Ratio (M‐H, Fixed, 95% CI)

1.05 [0.64, 1.73]

4 Clinical pregnancy rate Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Cumulatively

1

125

Odds Ratio (M‐H, Fixed, 95% CI)

1.08 [0.54, 2.19]

5 Multiple pregnancy rate Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 After first ET

2

1630

Odds Ratio (M‐H, Fixed, 95% CI)

1.11 [0.85, 1.44]

6 Miscarriage rate Show forest plot

4

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 After first ET

4

1892

Odds Ratio (M‐H, Fixed, 95% CI)

0.67 [0.52, 0.86]

7 Pregnancy complications Show forest plot

2

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

7.1 After first ET

2

1633

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.44 [1.08, 1.92]

8 Birth weight of babies born Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

8.1 Birth weight of singletons

1

462

Mean Difference (IV, Fixed, 95% CI)

161.80 [57.11, 266.49]

8.2 Birth weight of multiples

1

453

Mean Difference (IV, Fixed, 95% CI)

‐2.0 [‐94.08, 90.08]

Figures and Tables -
Comparison 1. Freeze‐all versus conventional IVF, outcomes per woman
Comparison 2. Freeze‐all versus conventional IVF, adverse events per clinical pregnancy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Multiple pregnancy Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 After first ET

2

939

Odds Ratio (M‐H, Fixed, 95% CI)

1.02 [0.77, 1.37]

2 Miscarriage Show forest plot

4

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 After first ET

4

1058

Odds Ratio (M‐H, Fixed, 95% CI)

0.56 [0.41, 0.77]

3 Pregnancy complications Show forest plot

2

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

3.1 After first ET

2

914

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.43 [1.05, 1.95]

Figures and Tables -
Comparison 2. Freeze‐all versus conventional IVF, adverse events per clinical pregnancy
Comparison 3. Freeze‐all versus conventional IVF, congenital abnormalities per live‐born children plus number of foetuses therapeutically terminated

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Congenital abnormalities Show forest plot

1

923

Odds Ratio (M‐H, Fixed, 95% CI)

1.25 [0.66, 2.37]

Figures and Tables -
Comparison 3. Freeze‐all versus conventional IVF, congenital abnormalities per live‐born children plus number of foetuses therapeutically terminated