To the Editor: We previously reported in the Journal1 the resultsof a randomized, controlled trial comparing pregnancy outcomesin patients undergoing in vitro fertilization (IVF) involvinga fresh single-embryo transfer followed, if no live birth occurredafter the fresh-embryo cycle, by a frozen-thawed single-embryotransfer with patients undergoing IVF involving a fresh double-embryotransfer. As compared with the rates in the double-embryo-transfergroup, in the single-embryo-transfer group, the live-birth ratewas not substantially lower and the multiple-birth rate wassignificantly lower.1 Multiple birth is considered to be themain risk associated with IVF because of the increased rateof adverse perinatal outcomes.2,3
The present study investigated the cumulative live-birth ratesin the two groups after the inclusion of all frozen-thawed cyclesafter the fresh-embryo cycle. The cumulative live-birth ratewas defined as the number of women with a pregnancy resultingin at least one live birth divided by the number of women whounderwent randomization. In the additional frozen-thawed cycles,one or two embryos were transferred, without regard to the originalrandomization group. All 661 patients who participated in therandomized trial were included; none of the patients were lostto follow-up, and all embryos were accounted for (Figure 1).
The patients in the single-embryo-transfer group underwent one fresh single-embryo transfer, and if no live birth occurred after one cycle, these patients underwent one frozen-thawed single-embryo transfer. Patients in the double-embryo-transfer group underwent one fresh double-embryo transfer. Twenty-nine patients in the single-embryo-transfer group and 18 patients in the double-embryo-transfer group had pregnancies resulting in two live births. One woman in the double-embryo-transfer group had a pregnancy resulting in three live births. The 48 pairs of twins in the double-embryo-transfer group after the first cycle included three twin pregnancies in which one fetus died in utero between 24 and 27 weeks of gestational age.
The cumulative live-birth rates were 43.9% (145 of 330 patients)in the single-embryo-transfer group and 51.1% (169 of 331 patients)in the double-embryo-transfer group (difference, 7.1%; 95% confidenceinterval [CI], –0.6 to 14.8; P=0.08). The mean rate oflive births was 53% (174 of 330 patients) in the single-embryo-transfergroup and 57% (189 of 331 patients) in the double-embryo-transfergroup (P=0.20). The multiple-birth rate was significantly lowerin the single-embryo-transfer group than in the double-embryo-transfergroup (2.3% vs. 27.5%; difference, 25.2%; 95% CI, 15.1 to 35.0;P<0.001). The rate of preterm birth (<37 full weeks ofgestational age) was significantly higher in the double-embryo-transfergroup as compared with the single-embryo-transfer group (25.5%vs. 11.8%; difference, 13.7%; 95% CI, 4.0 to 23.2; P<0.001)(see Table I in the Supplementary Appendix, available with thefull text of this letter at NEJM.org).
The use of cumulative live-birth rates instead of outcome percycle has advantages for the patient, since it better summarizesher chance of a live birth over an entire treatment period.4We found that the cumulative live-birth rate after one oocyteretrieval was high in both groups. It was lower in the single-embryo-transfergroup than in the double-embryo-transfer group, although notsignificantly so. The advantage of single-embryo transfer isthe dramatically reduced rate of multiple births as comparedwith double-embryo transfer. A well-functioning cryopreservationprogram is a prerequisite to implementation of a single-embryo-transferstrategy and should be encouraged.5
Ann Thurin-Kjellberg, M.D., Ph.D. Catharina Olivius, M.D. Christina Bergh, M.D., Ph.D. Gothenburg University Gothenburg, Sweden ann.thurin{at}vgregion.se
Supported by Sahlgrenska Academy, Sahlgrenska University Hospital,and the Göteborg Medical Society.
Dr. Thurin-Kjellberg reports receiving lecture fees from MerckSerono, Schering-Plough, and Ferring, and consulting fees fromMerck Serono Sweden; and Dr. Bergh, lecture fees from MerckSerono, Schering-Plough, and Ferring. No other potential conflictof interest relevant to this letter was reported.
References
Thurin-Kjellberg A, Hausken J, Hillensjö T, et al. Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization. N Engl J Med 2004;351:2392-2402. [Free Full Text]
Schieve LA, Meikle SF, Ferre C, Peterson HB, Jeng G, Wilcox LS. Low and very low birth weight in infants conceived with use of assisted reproductive technology. N Engl J Med 2002;346:731-737. [Free Full Text]
Wennerholm UB, Bergh C. Outcome of IVF pregnancies. Fetal Matern Med Rev 2004;15:27-57.
Malizia BA, Hacker MR, Penzias AS. Cumulative live-birth rates after in vitro fertilization. N Engl J Med 2009;360:236-243. [Free Full Text]
Veleva Z, Karinen P, Tomás C, Tapanainen J, Martikainen H. Elective single embryo transfer with cryopreservation improves the outcome and diminishes the costs of IVF/ICSI. Hum Reprod 2009;24:1632-1639. [Free Full Text]
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