Clinical effectiveness of elective single versus double embryo transfer: meta-analysis of individual patient data from randomised trials

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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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Most cited references 33

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Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses.

D Moher, D J Cook, S. Eastwood … (1999)

The Quality of Reporting of Meta-analyses (QUOROM) conference was convened to address standards for improving the quality of reporting of meta-analyses of clinical randomised controlled trials (RCTs). The QUOROM group consisted of 30 clinical epidemiologists, clinicians, statisticians, editors, and researchers. In conference, the group was asked to identify items they thought should be included in a checklist of standards. Whenever possible, checklist items were guided by research evidence suggesting that failure to adhere to the item proposed could lead to biased results. A modified Delphi technique was used in assessing candidate items. The conference resulted in the QUOROM statement, a checklist, and a flow diagram. The checklist describes our preferred way to present the abstract, introduction, methods, results, and discussion sections of a report of a meta-analysis. It is organised into 21 headings and subheadings regarding searches, selection, validity assessment, data abstraction, study characteristics, and quantitative data synthesis, and in the results with "trial flow", study characteristics, and quantitative data synthesis; research documentation was identified for eight of the 18 items. The flow diagram provides information about both the numbers of RCTs identified, included, and excluded and the reasons for exclusion of trials. We hope this report will generate further thought about ways to improve the quality of reports of meta-analyses of RCTs and that interested readers, reviewers, researchers, and editors will use the QUOROM statement and generate ideas for its improvement.

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Meta-analysis of the literature or of individual patient data: is there a difference?

L. Stewart, M Parmar (1993)

The use of meta-analyses or overviews to combine formally the results of related randomised clinical trials is becoming increasingly common. However the distinction between analyses based on information extracted from the published literature and those based on collecting and reanalysing updated individual patient data is not clear. We have investigated the difference between meta-analysis of the literature (MAL) and meta-analysis of individual patient data (MAP) by comparing the two approaches using randomised trials of cisplatin-based therapy in ovarian cancer. The MAL was based on 788 patients and the MAP on 1329 and estimated median follow-ups were 3.5 and 6.5 years, respectively. The MAL gave a result of greater statistical significance (p = 0.027 vs p = 0.30) and an estimate of absolute treatment effect three times as large as the MAP (7.5% vs 2.5%). Publication bias, patient exclusion, length of follow-up, and method of analysis all contributed to this observed difference. The results of a meta-analysis of the literature alone may be misleading. Whenever possible, a meta-analysis of updated individual patient data should be done because this provides the least biased and most reliable means of addressing questions that have not been satisfactorily resolved by individual clinical trials.

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Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization.

Anja Pinborg, Annika Strandell, Torbjörn Hillensjö … (2004)

The risks of premature birth and perinatal death are increased after in vitro fertilization. These risks are mainly due to the high incidence of multiple births, which relates to the number of embryos transferred. We performed a randomized, multicenter trial to assess the equivalence of two approaches to in vitro fertilization with respect to the rates of pregnancy that result in at least one live birth and to compare associated rates of multiple gestation. Women less than 36 years of age who had at least two good-quality embryos were randomly assigned either to undergo transfer of a single fresh embryo and, if there was no live birth, subsequent transfer of a single frozen-and-thawed embryo, or to undergo a single transfer of two fresh embryos. Equivalence was defined as a difference of no more than 10 percentage points in the rates of pregnancy resulting in at least one live birth. Pregnancy resulting in at least one live birth occurred in 142 of 331 women (42.9 percent) in the double-embryo-transfer group as compared with 128 of 330 women (38.8 percent) in the single-embryo-transfer group (difference, 4.1 percentage points; 95 percent confidence interval, -3.4 to 11.6 percentage points); rates of multiple births were 33.1 percent and 0.8 percent, respectively (P<0.001). These results do not demonstrate equivalence of the two approaches in rates of live births, but they do indicate that any reduction in the rate of live births with the transfer of single embryos is unlikely to exceed 11.6 percentage points. In women under 36 years of age, transferring one fresh embryo and then, if needed, one frozen-and-thawed embryo dramatically reduces the rate of multiple births while achieving a rate of live births that is not substantially lower than the rate that is achievable with a double-embryo transfer. Copyright 2004 Massachusetts Medical Society.

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Author and article information

Contributors

: Role: research fellow

: Role: professor

: Role: associate professor

: Role: medical director

: Role: head of IVF laboratory

: Role: sector manager

: Role: professor in reproductive medicine

: Role: chief physician

: Role: professor of obstetrics and gynaecology

: Role: professor

: Role: senior consultant

: Role: professor of reproductive medicine

: Role: research fellow

: Role: resident in obstetrics and gynaecology

: Role: scientific director

: Role: professor of reproductive medicine

Journal

Journal ID (nlm-ta): BMJ

Journal ID (publisher-id): bmj

Title: BMJ : British Medical Journal

Publisher: BMJ Publishing Group Ltd.

ISSN (Print): 0959-8138

ISSN (Electronic): 1468-5833

Publication date Collection: 2010

Publication date (Print): 2010

Publication date (Electronic): 21 December 2010

Volume: 341

Electronic Location Identifier: c6945

Affiliations

[1 ]Medical Statistics Team, Section of Population Health, University of Aberdeen, Aberdeen AB25 2ZD, UK

[2 ]Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska University Hospital, Gothenburg, Sweden

[3 ]Robinson Institute, Discipline of Obstetrics and Gynaecology, University of Adelaide, South Australia 5005, Australia

[4 ]Centre for Reproductive Medicine, ZNA Middelheim Hospital, Antwerp, Belgium

[5 ]Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht, Netherlands

[6 ]Sector Man, Women and Child, Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, University Hospital Ghent, Ghent, Belgium

[7 ]Radboud University Nijmegen Medical Centre, 791 Obstetrics and Gynaecology, Nijmegen, Netherlands

[8 ]Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology and Infertility, University of Oulu, Oulu, Finland

[9 ]Department of Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, Netherlands

[10 ]Discipline of Obstetrics and Gynaecology, University of Adelaide, South Australia

[11 ]Helsinki University, Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland

[12 ]IVF Laboratory, Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht

[13 ]Applied Clinical Sciences, Division of Applied Health Sciences, School of Medicine and Dentistry, University of Aberdeen, Aberdeen Maternity Hospital, Aberdeen

Author notes

Correspondence to: D J McLernon d.mclernon@ 123456abdn.ac.uk

Article

Publisher ID: mcld782771

DOI: 10.1136/bmj.c6945

PMC ID: 3006495

PubMed ID: 21177530

SO-VID: a97d35ed-8c0c-45c6-9f4e-2e2615953947

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This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

Clinical effectiveness of elective single versus double embryo transfer: meta-analysis of individual patient data from randomised trials

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Most cited references 33

Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses.

Meta-analysis of the literature or of individual patient data: is there a difference?

Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization.

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