Criteria for number of embryos to transfer: a committee opinion The Practice Committee of the American Society for Reproductive Medicine and the Practice Committee of the Society for Assisted Reproductive Technology American Society for Reproductive Medicine and Society for Assisted Reproductive Technology, Birmingham, Alabama Based on American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology data available for 2010, ASRM's guidelines for the number of embryos to be transferred in in vitro fertilization cycles have been further refined in continuing efforts to reduce the number of higher-order mulUse your smartphone tiple pregnancies. This version replaces the document titled Guidelines on number of embryos to scan this QR code transferred that was published most recently in August of 2009, Fertil Steril 2009;92:1518–9. and connect to the (Fertil SterilÒ 2013;99:44–6. Ó2013 by American Society for Reproductive Medicine.) Discuss: You can discuss this article with its authors and with other ASRM members at http:// fertstertforum.com/goldsteinj-guidelines-embryos-transferred-committee-opinion/ B ased on American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART) data available for 2010, ASRM's guidelines for the number of embryos to be transferred in in vitro fertilization (IVF) cycles were revised in an effort to reduce the number of higher-order multiple pregnancies. High-order multiple pregnancy (three or more implanted embryos) is an undesirable consequence (outcome) of assisted reproductive technologies (ART) (1). Multiple gestations lead to an increased risk of complications in both the fetuses and the mothers (2). Ideally, the goal of ART is to achieve a singleton gestation (3, 4). Although multifetal pregnancy reduction can be performed to reduce fetal number, the procedure may result in the loss of all fetuses, does not completely eliminate the risks associated with multiple pregnancy, and may have adverse psychological consequences (5). Moreover, multifetal pregnancy reduction is not an acceptable option for many women. In an effort to reduce the incidence of high-order multiple gestations and promote singleton gestations, ASRM and SART have developed the following guidelines to assist ART programs and patients in determining the appropriate number of cleavage-stage (usually 2 or 3 days after fertilization) embryos or blastocysts (usually 5 or 6 days after fertilization) to transfer. Strict limitations on the number of embryos transferred, as required by law in some countries, do not allow treatment plans to be individualized after careful consideration of each patient's own unique circumstances. Therefore, transferring greater or fewer embryos than dicatated by these criteria may be justified according to individual clinical conditions, including patient age, embryo quality, the opportunity for cryopreservation, and as clinical experience with newer techniques accumulates. I. Individual programs are encouraged to generate and use their own data regarding patient characteristics Received September 19, 2012; accepted September 21, 2012; published online October 22, 2012. No reprints will be available. Correspondence: Practice Committee, American Society for Reproductive Medicine, 1209 Montgomery Hwy., Birmingham, AL 35216 (E-mail: ASRM@asrm.org). Fertility and Sterility® Vol. 99, No. 1, January 2013 0015-0282/$36.00 Copyright ©2013 American Society for Reproductive Medicine, Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fertnstert.2012.09.038 44 discussion forum for this article now.* * Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace. 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. Programs that have a high-order multiple pregnancy rate that is >2 standard deviations above the mean rate for all SART-reporting clinics for 2 consecutive years may be audited by SART. II. Independent of age, the following characteristics have been associated with a favorable prognosis: 1) first cycle of IVF; 2) good-quality embryos as judged by morphologic criteria; and 3) excess embryos of sufficient quality to warrant cryopreservation. Patients who have had previous success with IVF also should be regarded as being in a favorable prognostic category. The number of embryos transferred should be agreed upon by the physician and the treated patient(s), informed consent documents completed, and the information recorded in the clinical record. In the absence of data generated by the individual program, and based on data generated by all clinics providing ART services, the following guidelines are recommended (Table 1): A. Patients under the age of 35 who have a favorable prognosis VOL. 99 NO. 1 / JANUARY 2013 Fertility and Sterility® TABLE 1 Recommended limits on the numbers of embryos to transfer. Age (y) Prognosis <35 35–37 38–40 41–42 1–2 2 2 3 3 4 5 5 1 2 2 2 2 3 3 3 a Cleavage-stage embryos Favorableb All others Blastocystsa Favorableb All others a b See text for more complete explanations. Justification for transferring one additional embryo more than the recommended limit should be clearly documented in the patient's medical record. Favorable ¼ first cycle of IVF, good embryo quality, excess embryos available for cryopreservation, or previous successful IVF cycle. Practice Committee. Pharmacogenetic approach to male infertility. Fertil Steril 2013. B. C. D. E. F. G. H. should be offered a single-embryo transfer and no more than two embryos (cleavage stage or blastocyst) should be transferred (4, 6). If two embryos are transferred, the patient(s) must be counseled regarding the risks of multifetal pregnancy and the counseling should be documented in the patient's permanent medical record. For patients between 35 and 37 years of age who have a favorable prognosis, no more than two cleavagestage embryos should be transferred. All others in this age group should have no more than three cleavagestage embryos transferred. If extended culture is performed, no more than two blastocysts should be transferred to women in this age group. For patients between 38 and 40 years of age who have a favorable prognosis, no more than three cleavagestage embryos or two blastocysts should be transferred. All others in this age group should have no more than four cleavage-stage embryos or three blastocysts transferred. For patients 41–42 years of age, no more than five cleavage-stage embryos or three blastocyts should be transferred. In each of the above age groups, for patients with two or more previous failed fresh IVF cycles or a less favorable prognosis, one additional embryo may be transferred according to individual circumstances. The patient must be counseled regarding the risks of multifetal pregnancy. Both the counseling and the justification for exceeding the recommended limits must be documented in the patient(s)'s permanent medical record. In women >43 years of age, there are insufficient data to recommend a limit on the number of embryos to transfer. In donor-egg cycles, the age of the donor should be used to determine the appropriate number of embryos to transfer, but when the donor is <35 years of age single embryo transfer should be strongly considered. In frozen-embryo transfer cycles, the number of goodquality thawed embryos transferred should not exceed the recommended limit on the number of fresh embryos transferred for each age group. VOL. 99 NO. 1 / JANUARY 2013 III. Because not all oocytes may fertilize when gamete intrafallopian transfer is performed, one more oocyte than embryo may be transferred for each prognostic category (7). Acknowledgments: This report was developed under the direction of the Practice Committee of the American Society for Reproductive Medicine as a service to its members and other practicing clinicians. Although this document reflects appropriate management of a problem encountered in the practice of reproductive medicine, it is not intended to be the only approved standard of practice or to dictate an exclusive course of treatment. Other plans of management may be appropriate, taking into account the needs of the individual patient, available resources, and institutional or clinical practice limitations. The Practice Committee and the Board of Directors of the American Society for Reproductive Medicine have approved this report. This document was reviewed by ASRM members and their input was considered in the preparation of the final document. The following members of the ASRM Practice Committee participated in the development of this document. All Committee members disclosed commercial and financial relationships with manufacturers or distributors of goods or services used to treat patients. Members of the Committee who were found to have conflicts of interest based on the relationships disclosed did not participate in the discussion or development of this document. Samantha Pfeifer, M.D.; Marc Fritz, M.D.; Jeffrey Goldberg, M.D.; Roger Lobo, M.D.; R. Dale McClure, M.D.; Michael Thomas, M.D.; Eric Widra, M.D.; Glenn Schattman, M.D.; Mark Licht, M.D.; John Collins, M.D.; Marcelle Cedars, M.D.; Catherine Racowsky, PhD.; Michael Vernon, M.D.; Owen Davis, M.D.; Kurt Barnhart, M.D., M.S.C.E.; Clarisa Gracia, M.D., M.S.C.E.; William Catherino, M.D., Ph.D.; Robert Rebar, M.D.; Andrew La Barbera, Ph.D. REFERENCES 1. Society for Assisted Reproductive Technology, American Society for Reproductive Medicine. Assisted reproductive technology in the United States: 2010 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Available at: https://www.sartcorsonline. com/rptCSR_PublicMultYear.aspx?ClinicPKID¼0. Last accessed September 27, 2012. 45 ASRM PAGES 2. 3. 4. 46 Sunderam S, Chang J, Flowers L, Kulkarni A, Sentelle G, Jeng G, Macaluso M, et al. Assisted reproductive technology surveillance–United States, 2006. MMWR Surveill Summ 2009;58:1–25. Practice Committee of American Society for Reproductive Medicine. Multiple gestation associated with infertility therapy: an American Society for Reproductive Medicine Practice Committee opinion. Fertil Steril 2012;97:825–34. Practice Committee of Society for Assisted Reproductive Technology, Practice Committee of American Society for Reproductive Medicine. Elective singleembryo transfer. Fertil Steril 2012;97:835–42. 5. 6. 7. Stone J, Eddleman K, Lynch L, Berkowitz RL. A single center experience with 1000 consecutive cases of multifetal pregnancy reduction. Am J Obstet Gynecol 2002;187:1163–7. Pandian Z, Bhattacharya S, Ozturk O, Serour G, Templeton A. Number of embryos for transfer following in-vitro fertilization or intra-cytoplasmic sperm injection. Cochrane Database Syst Rev 2009;2:CD003416. Qasim SM, Karacan M, Corsan GH, Shelden R, Kemmann E. High-order oocyte transfer in gamete intrafallopian transfer patients 40 or more years of age. Fertil Steril 1995;64:107–10. VOL. 99 NO. 1 / JANUARY 2013