Elective single embryo transfer (eSET) for all patients?

Debate The development of culture techniques that allowed more embryos to develop to the blastocyst stage has made the implementation of eSET more imperative and sound medicine, as the implantation of these embryos is high. Many centres in the world presently accept that blastocyst technology need to be developed in all possible cycles, with protocols set to increase the number of cycles with blastocysts and in such case to implement eSET for women <38 years and even in women <40 years. The European experience even advice that cleaved (day 3) eSET for women <37 years will result in similar cumulative live birth to double ET (day 3) with a significant reduction in twin pregnancies. In UK the HFEA advices that women <40 years of age are only to have 2 or less embryos to be transferred at a time and that eSET to be implemented on all transfers in order to reduce multiple pregnancies to <10%. It is incumbent on all of us as specialist in the field of Reproductive Medicine to ensure the safety of our patients including the children resulting from our treatment. The evidence is overwhelming that we have to reduce multiple pregnancies to improve the outcome of ART. We have to improve our clinical and laboratory environment and increase the practice of eSET. It is important for MEFS and its members to promote and educate all practitioners in the Middle East that transferring more embryos in each cycle only indicate poor practice and low quality care. Patients need to be informed that they need to ask for a quality care that offers them a more successful result with adopting single live birth as the measure of success. References (1) Multiple Pregnancy Following Assisted reproduction. Royal College of Obstetricians and Gynaecologists, Scientific Advisory Committee Opinion Paper 22. (2) Assisted Reproductive Technology Success Rates National Summary and Fertility Clinic Reports. CDC 2008 Report. (3) Report of Expert Group on Multiple Births after IVF, HFEA 2005. (4) Pandian Z, Bhattacharya S, Ozturk O, Serour G, Templeton A. Number of embryos for transfer following in-vitro fertilisation or intra-cytoplasmic sperm injection (Review). The Cochrane Collaboration 2009. (5) Gelbaya TA, Tsoumpou I, Nardo LG. The likelihood of live birth and multiple birth after single versus double embryo transfer at the cleavage stage: a systematic review and meta-analysis. Fertil Steril 2010;94(3):936–45. (6) Clinical effectiveness of elective single versus double embryo transfer: meta-analysis of individual patient data from randomised trials 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. BMJ 2010;341: 1336–45. Talha Al-Shawaf Barts and the London Centre for Reproductive Medicine, Barts and The London NHS Trust, St Bartholomew’s Hospital, West Smithfield, London EC1A 7BE, UK E-mail addresses: Talha.Al-Shawaf@bartsandthelondon.nhs.uk 185 Comment by: Ahmed Nasr 1. Introduction Almost one third of a century has swiftly elapsed since the delivery of the first IVF baby, Louise Brown, back in 1978. Since then, more than four million babies have been brought to life with the assistance of IVF worldwide. Having unveiled many of the secrets of human reproduction on their way to success with IVF, the medical visionaries, Edwards and Steptoe, quelled the vitriolic critics with their outstanding achievement. Akin to all other breakthroughs in medicine, IVF has been surrounded by a great deal of reverence, admiration and veneration on the one hand with some skepticism, incredulity and disparagement on the other. Louise Brown emerged from a compulsory single embryo transfer (SET) with no other choice than to transfer one embryo. With continuing refinements in ART techniques, the conventional policy has been to transfer three or more embryos in the hope of maximizing success. This strategy has resulted in an unfortunate increase in the rate of twinning and high-order multiple pregnancies. This has not only increased costs to the health service but has also brought about an endless list of maternal and neonatal complications. The famous Los Angeles resident Nadya Suleman’s octuplet pregnancy with eight babies born after IVF treatment is but one existing example. To reduce such potential threats to an absolute minimum, elective single embryo transfer (eSET) has been proposed. Such women do have several embryos available for transfer, but deliberately only one embryo is transferred. Elective SET remains the most operational way of reducing the ever-rising multiple pregnancy rates associated with ART. Other potential options include multifetal pregnancy reduction. However, this technique is skill-demanding, may not completely abolish the risks associated with multiple pregnancy, may end up in the dreaded loss of all fetuses and may be unappealing and indeed psychologically devastating to many women (1). SET is a mimic-to-nature endeavor. Published evidence proposes that prudent adoption of an eSET strategy can almost annul the chances of multiples without compromising cumulative live birth rates (2). Elective SET shows acceptable pregnancy rates; the somewhat lower rates in comparison with double embryo transfer (DET) are compensated by the possibility to cryopreserve one or more embryos after eSET for subsequent cycles (3). Moreover, even in singleton pregnancy after ART, outcomes are less favorable when compared with naturally conceived singletons. Currently, there is growing evidence that eSET may be an answer to the less advantageous outcome in singletons after ART (3). However, global application of eSET remains a contentious issue and a unanimous universal consensus on its adoption is a yet-to-be-achieved goal. Unanswered remains the all-important question of when to apply eSET. The currently available evidence is far from being inclusive or complete for practicing gynecologists and IVF specialists. 2. Should eSET be adopted ‘selectively’ or rather ‘indiscriminately’? A multitude of potential factors govern the implementation of the eSET policy. Those include woman characteristics, fiscal 186 dilemmas (access to public funding for ART), availability of satisfactory cryopreservation facilities, legislation and personal inclinations as many infertile couples opt for twins (2). A randomized, multicenter trial has shown that 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 DET (4). Similarly in the UK, the British Fertility Society (BFS) and the Association of Clinical Embryologists (ACE) have issued new guidelines recommending that in women under the age of 37, in their first IVF cycle who have several high quality embryos eSET plus subsequent frozen embryo transfer can be as effective as DET, and does not compromise the likelihood of conception. It is essential to combine an eSET policy with an effective frozen embryo replacement program to maximize cumulative live birth rates per stimulated cycle (5). Joint guidelines proposed by the practice committees of the ASRM and the SART on number of embryos transferred recommend individualized programs to generate and use their own data regarding patient characteristics and the number of embryos to be transferred. Accordingly, programs should monitor their results continually and adjust the number of embryos transferred to minimize undesirable outcomes (1). Independent of age, favorable prognostic factors include: first cycle of IVF, women who have had previous success with IVF, good-quality embryos as judged by morphologic criteria and excess embryos of sufficient quality to warrant cryopreservation. The number of embryos transferred should be agreed upon by the physician and the treated woman with an informed consent (1). Women under the age of 35 who have a more favorable prognosis are considered for eSET; no more than two embryos (cleavage-stage or blastocyst) should be transferred. In women between 35 and 37 years of age who have a more favorable prognosis, no more than two cleavage-stage embryos should be transferred. All other women in this age group with an unfavorable prognosis should have no more than three cleavagestage embryos transferred; if extended culture is performed, no more than two blastocysts should be transferred (1). For women between 38 and 40 years of age who have a more favorable prognosis, no more than three cleavage-stage embryos or two blastocysts should be transferred. All others in this age group should have no more than four cleavagestage embryos or three blastocysts transferred. In women aged 41–42 years, no more than five cleavage-stage embryos or three blastocysts should be transferred. For all the abovementioned age groups, women with P2 previous failed fresh IVF cycles or a less favorable prognosis, one additional embryo may be transferred according to individual circumstances, given adequate counseling is provided. In women P43 years of age, there are insufficient data to recommend a limit on the number of embryos to transfer. In frozen embryo transfer cycles, the number of good-quality thawed embryos transferred should not exceed the recommended limit on the number of fresh embryos transferred for each age group (1). The usage of eSET is highest in Sweden (69.4%), but as low as 2.8% in the USA (2). Legislative amendments might help bridge such significant gaps. Any birth of multiples increases Debate the risk of complications to mothers and their babies as well as healthcare costs. Many couples would rather opt to have twins or triplets than to spend more money on multiple SETs to build their families. Down the road, many challenges still hinder advancement of IVF practice; one of the most salient is to find a satisfactory compromise between effectiveness and cost-effectiveness on the one hand and avoidance of potential risks on the other. Conclusively, not all women can potentially become ‘ideal’ candidates for implementing the eSET strategy. It is intriguing at this juncture that the discerning IVF specialist should stand the difficult test of making choices. 3. Conclusion The critical issue of universal adoption of eSET remains unresolved. Significant variations in its application among different countries around the globe testify to this thesis. Pragmatic application of eSET for all women is arguable. Elective SET should not be considered ‘routine’. Selective adoption is a policy that should be commended and invigorated. This is particularly pertinent to developing nations, where the cost-benefit balance has to be seriously taken into consideration. In this context, the interplay of many other personal, fiscal and legislative influences has to be kept in perspective. Availability of satisfactory cryopreservation facilities is pivotal for eSET practice. The final decision as whether or not to electively transfer a single embryo should not only be taken by the vigilant IVF specialist, who is well aware of the various aspects of this multifaceted dilemma, but also by the concerned woman, or more correctly couple. Consequently, the vital role of satisfactory counseling cannot be overemphasized. References (1) Practice Committee of the American Society for Reproductive Medicine; Practice Committee of the Society for Assisted Reproductive Technology. Guidelines on number of embryos transferred. Fertil Steril 2009;92(5):1518–9. (2) Maheshwari A, Griffiths S, Bhattacharya S. Global variations in the uptake of single embryo transfer. Hum Reprod Update 2011;17(1):107–20. (3) Ilse D, Petra D, Jan G, Marleen T. Single embryo transfer: double remedy for complications after assisted reproduction. Curr Womens Health Rev 2008;4:218–22. (4) Thurin A, Hausken J, Hillensjö T, Jablonowska B, Pinborg A, Strandell A, Bergh C. Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization. N Engl J Med 2004;351(23):2392–402. (5) Cutting R, Morroll D, Roberts SA, Pickering S, Rutherford A. BFS and ACE. Elective single embryo transfer: guidelines for practice British Fertility Society and Association of Clinical Embryologists. Hum Fertil (Camb) 2008;11(3):131–46. Ahmed Nasr Women’s Health Center, Department of Obstetrics and Gynecology, Faculty of Medicine, Assiut University, P.O. Box 1, 71516 Assiut, Egypt E-mail addresses: a_nasr02@lycos.com