Clinical effectiveness of elective single versus double embryo transfer

meta-analysis of individual patient data from randomised trials

D J McLernon, K Harrild, C Bergh, M J Davies, D de Neubourg, J C M Dumoulin, J Gerris, J A M Kremer, H Martikainen, B W Mol, R J Norman, A Thurin-Kjellberg, A Tiitinen, A P A van Montfoort, A M van Peperstraten, E Van Royen, S Bhattacharya

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Objective To compare the effectiveness of elective single embryo transfer versus double embryo transfer on the outcomes of live birth, multiple live birth, miscarriage, preterm birth, term singleton birth, and low birth weight after fresh embryo transfer, and on the outcomes of cumulative live birth and multiple live birth after fresh and frozen embryo transfers.

Design One stage meta-analysis of individual patient data.

Data sources A systematic review of English and non-English articles from Medline, Embase, and the Cochrane Central Register of Controlled Trials (up to 2008). Additional studies were identified by contact with clinical experts and searches of bibliographies of all relevant primary articles. Search terms included embryo transfer, randomised controlled trial, controlled clinical trial, single embryo transfer, and double embryo transfer.

Review methods Comparisons of the clinical effectiveness of cleavage stage (day 2 or 3) elective single versus double embryo transfer after fresh or frozen in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatments were included. Trials were included if the intervention differed only in terms of the intended number of embryos to be transferred. Trials that involved only blastocyst (day five) transfers were excluded.

Results Individual patient data were received for every patient recruited to all eight eligible trials (n=1367). A total of 683 and 684 women randomised to the single and double embryo transfer arms, respectively, were included in the analysis. Baseline characteristics in the two groups were comparable. The overall live birth rate in a fresh IVF cycle was lower after single (181/683, 27%) than double embryo transfer (285/683, 42%) (adjusted odds ratio 0.50, 95% confidence interval 0.39 to 0.63), as was the multiple birth rate (3/181 (2%) v 84/285 (29%)) (0.04, 0.01 to 0.12). An additional frozen single embryo transfer, however, resulted in a cumulative live birth rate not significantly lower than the rate after one fresh double embryo transfer (132/350 (38%) v 149/353 (42%) (0.85, 0.62 to 1.15), with a minimal cumulative risk of multiple birth (1/132 (1%) v 47/149 (32%)). The odds of a term singleton birth (that is, over 37 weeks) after elective single embryo transfer was almost five times higher than the odds after double embryo transfer (4.93, 2.98 to 8.18).

Conclusions Elective single embryo transfer results in a higher chance of delivering a term singleton live birth compared with double embryo transfer. Although this strategy yields a lower pregnancy rate than a double embryo transfer in a fresh IVF cycle, this difference is almost completely overcome by an additional frozen single embryo transfer cycle. The multiple pregnancy rate after elective single embryo transfer is comparable with that observed in spontaneous pregnancies.
Original languageEnglish
Article numberc6945
Number of pages13
JournalBritish Medical Journal
Volume341
Issue number-
DOIs
Publication statusPublished - 21 Dec 2010

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Embryo Transfer
Single Embryo Transfer
Meta-Analysis
Live Birth
Multiple Birth Offspring
Birth Rate
Fertilization in Vitro
Term Birth
Pregnancy Rate
Multiple Pregnancy
Intracytoplasmic Sperm Injections
Information Storage and Retrieval
Premature Birth
Controlled Clinical Trials
Bibliography
Low Birth Weight Infant
Blastocyst
Spontaneous Abortion
Embryonic Structures
Randomized Controlled Trials

Keywords

  • abortion, spontaneous
  • adult
  • embryo transfer
  • female
  • fertilization in vitro
  • humans
  • live birth
  • maternal age
  • pregnancy
  • pregnancy rate
  • pregnancy, multiple
  • randomized controlled trials as topic

Cite this

Clinical effectiveness of elective single versus double embryo transfer : meta-analysis of individual patient data from randomised trials. / McLernon, D J; Harrild, K; Bergh, C; Davies, M J; de Neubourg, D; Dumoulin, J C M; Gerris, J; Kremer, J A M; Martikainen, H; Mol, B W; Norman, R J; Thurin-Kjellberg, A; Tiitinen, A; van Montfoort, A P A; van Peperstraten, A M; Van Royen, E; Bhattacharya, S.

In: British Medical Journal, Vol. 341, No. -, c6945, 21.12.2010.

Research output: Contribution to journalArticle

McLernon, DJ, Harrild, K, Bergh, C, Davies, MJ, de Neubourg, D, Dumoulin, JCM, Gerris, J, Kremer, JAM, Martikainen, H, Mol, BW, Norman, RJ, Thurin-Kjellberg, A, Tiitinen, A, van Montfoort, APA, van Peperstraten, AM, Van Royen, E & Bhattacharya, S 2010, 'Clinical effectiveness of elective single versus double embryo transfer: meta-analysis of individual patient data from randomised trials', British Medical Journal, vol. 341, no. -, c6945. https://doi.org/10.1136/bmj.c6945
McLernon, D J ; Harrild, K ; Bergh, C ; Davies, M J ; de Neubourg, D ; Dumoulin, J C M ; Gerris, J ; Kremer, J A M ; Martikainen, H ; Mol, B W ; Norman, R J ; Thurin-Kjellberg, A ; Tiitinen, A ; van Montfoort, A P A ; van Peperstraten, A M ; Van Royen, E ; Bhattacharya, S. / Clinical effectiveness of elective single versus double embryo transfer : meta-analysis of individual patient data from randomised trials. In: British Medical Journal. 2010 ; Vol. 341, No. -.
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abstract = "Objective To compare the effectiveness of elective single embryo transfer versus double embryo transfer on the outcomes of live birth, multiple live birth, miscarriage, preterm birth, term singleton birth, and low birth weight after fresh embryo transfer, and on the outcomes of cumulative live birth and multiple live birth after fresh and frozen embryo transfers.Design One stage meta-analysis of individual patient data.Data sources A systematic review of English and non-English articles from Medline, Embase, and the Cochrane Central Register of Controlled Trials (up to 2008). Additional studies were identified by contact with clinical experts and searches of bibliographies of all relevant primary articles. Search terms included embryo transfer, randomised controlled trial, controlled clinical trial, single embryo transfer, and double embryo transfer.Review methods Comparisons of the clinical effectiveness of cleavage stage (day 2 or 3) elective single versus double embryo transfer after fresh or frozen in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatments were included. Trials were included if the intervention differed only in terms of the intended number of embryos to be transferred. Trials that involved only blastocyst (day five) transfers were excluded.Results Individual patient data were received for every patient recruited to all eight eligible trials (n=1367). A total of 683 and 684 women randomised to the single and double embryo transfer arms, respectively, were included in the analysis. Baseline characteristics in the two groups were comparable. The overall live birth rate in a fresh IVF cycle was lower after single (181/683, 27{\%}) than double embryo transfer (285/683, 42{\%}) (adjusted odds ratio 0.50, 95{\%} confidence interval 0.39 to 0.63), as was the multiple birth rate (3/181 (2{\%}) v 84/285 (29{\%})) (0.04, 0.01 to 0.12). An additional frozen single embryo transfer, however, resulted in a cumulative live birth rate not significantly lower than the rate after one fresh double embryo transfer (132/350 (38{\%}) v 149/353 (42{\%}) (0.85, 0.62 to 1.15), with a minimal cumulative risk of multiple birth (1/132 (1{\%}) v 47/149 (32{\%})). The odds of a term singleton birth (that is, over 37 weeks) after elective single embryo transfer was almost five times higher than the odds after double embryo transfer (4.93, 2.98 to 8.18).Conclusions Elective single embryo transfer results in a higher chance of delivering a term singleton live birth compared with double embryo transfer. Although this strategy yields a lower pregnancy rate than a double embryo transfer in a fresh IVF cycle, this difference is almost completely overcome by an additional frozen single embryo transfer cycle. The multiple pregnancy rate after elective single embryo transfer is comparable with that observed in spontaneous pregnancies.",
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TY - JOUR

T1 - Clinical effectiveness of elective single versus double embryo transfer

T2 - meta-analysis of individual patient data from randomised trials

AU - McLernon, D J

AU - Harrild, K

AU - Bergh, C

AU - Davies, M J

AU - de Neubourg, D

AU - Dumoulin, J C M

AU - Gerris, J

AU - Kremer, J A M

AU - Martikainen, H

AU - Mol, B W

AU - Norman, R J

AU - Thurin-Kjellberg, A

AU - Tiitinen, A

AU - van Montfoort, A P A

AU - van Peperstraten, A M

AU - Van Royen, E

AU - Bhattacharya, S

PY - 2010/12/21

Y1 - 2010/12/21

N2 - Objective To compare the effectiveness of elective single embryo transfer versus double embryo transfer on the outcomes of live birth, multiple live birth, miscarriage, preterm birth, term singleton birth, and low birth weight after fresh embryo transfer, and on the outcomes of cumulative live birth and multiple live birth after fresh and frozen embryo transfers.Design One stage meta-analysis of individual patient data.Data sources A systematic review of English and non-English articles from Medline, Embase, and the Cochrane Central Register of Controlled Trials (up to 2008). Additional studies were identified by contact with clinical experts and searches of bibliographies of all relevant primary articles. Search terms included embryo transfer, randomised controlled trial, controlled clinical trial, single embryo transfer, and double embryo transfer.Review methods Comparisons of the clinical effectiveness of cleavage stage (day 2 or 3) elective single versus double embryo transfer after fresh or frozen in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatments were included. Trials were included if the intervention differed only in terms of the intended number of embryos to be transferred. Trials that involved only blastocyst (day five) transfers were excluded.Results Individual patient data were received for every patient recruited to all eight eligible trials (n=1367). A total of 683 and 684 women randomised to the single and double embryo transfer arms, respectively, were included in the analysis. Baseline characteristics in the two groups were comparable. The overall live birth rate in a fresh IVF cycle was lower after single (181/683, 27%) than double embryo transfer (285/683, 42%) (adjusted odds ratio 0.50, 95% confidence interval 0.39 to 0.63), as was the multiple birth rate (3/181 (2%) v 84/285 (29%)) (0.04, 0.01 to 0.12). An additional frozen single embryo transfer, however, resulted in a cumulative live birth rate not significantly lower than the rate after one fresh double embryo transfer (132/350 (38%) v 149/353 (42%) (0.85, 0.62 to 1.15), with a minimal cumulative risk of multiple birth (1/132 (1%) v 47/149 (32%)). The odds of a term singleton birth (that is, over 37 weeks) after elective single embryo transfer was almost five times higher than the odds after double embryo transfer (4.93, 2.98 to 8.18).Conclusions Elective single embryo transfer results in a higher chance of delivering a term singleton live birth compared with double embryo transfer. Although this strategy yields a lower pregnancy rate than a double embryo transfer in a fresh IVF cycle, this difference is almost completely overcome by an additional frozen single embryo transfer cycle. The multiple pregnancy rate after elective single embryo transfer is comparable with that observed in spontaneous pregnancies.

AB - Objective To compare the effectiveness of elective single embryo transfer versus double embryo transfer on the outcomes of live birth, multiple live birth, miscarriage, preterm birth, term singleton birth, and low birth weight after fresh embryo transfer, and on the outcomes of cumulative live birth and multiple live birth after fresh and frozen embryo transfers.Design One stage meta-analysis of individual patient data.Data sources A systematic review of English and non-English articles from Medline, Embase, and the Cochrane Central Register of Controlled Trials (up to 2008). Additional studies were identified by contact with clinical experts and searches of bibliographies of all relevant primary articles. Search terms included embryo transfer, randomised controlled trial, controlled clinical trial, single embryo transfer, and double embryo transfer.Review methods Comparisons of the clinical effectiveness of cleavage stage (day 2 or 3) elective single versus double embryo transfer after fresh or frozen in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatments were included. Trials were included if the intervention differed only in terms of the intended number of embryos to be transferred. Trials that involved only blastocyst (day five) transfers were excluded.Results Individual patient data were received for every patient recruited to all eight eligible trials (n=1367). A total of 683 and 684 women randomised to the single and double embryo transfer arms, respectively, were included in the analysis. Baseline characteristics in the two groups were comparable. The overall live birth rate in a fresh IVF cycle was lower after single (181/683, 27%) than double embryo transfer (285/683, 42%) (adjusted odds ratio 0.50, 95% confidence interval 0.39 to 0.63), as was the multiple birth rate (3/181 (2%) v 84/285 (29%)) (0.04, 0.01 to 0.12). An additional frozen single embryo transfer, however, resulted in a cumulative live birth rate not significantly lower than the rate after one fresh double embryo transfer (132/350 (38%) v 149/353 (42%) (0.85, 0.62 to 1.15), with a minimal cumulative risk of multiple birth (1/132 (1%) v 47/149 (32%)). The odds of a term singleton birth (that is, over 37 weeks) after elective single embryo transfer was almost five times higher than the odds after double embryo transfer (4.93, 2.98 to 8.18).Conclusions Elective single embryo transfer results in a higher chance of delivering a term singleton live birth compared with double embryo transfer. Although this strategy yields a lower pregnancy rate than a double embryo transfer in a fresh IVF cycle, this difference is almost completely overcome by an additional frozen single embryo transfer cycle. The multiple pregnancy rate after elective single embryo transfer is comparable with that observed in spontaneous pregnancies.

KW - abortion, spontaneous

KW - adult

KW - embryo transfer

KW - female

KW - fertilization in vitro

KW - humans

KW - live birth

KW - maternal age

KW - pregnancy

KW - pregnancy rate

KW - pregnancy, multiple

KW - randomized controlled trials as topic

U2 - 10.1136/bmj.c6945

DO - 10.1136/bmj.c6945

M3 - Article

VL - 341

JO - BMJ

JF - BMJ

SN - 0959-8146

IS - -

M1 - c6945

ER -