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Innovations in assisted reproductive technologies: impact on contemporary donor egg practice and future advances

2018; Elsevier BV; Volume: 110; Issue: 6 Linguagem: Inglês

10.1016/j.fertnstert.2018.09.020

1556-5653

Mindy S. Christianson, José Bellver,

Ovarian function and disorders

Innovations in assisted reproductive technologies (ART) have driven progress in the donor egg field since the birth of the first baby derived from a donor egg in 1983. Over time, donor oocytes have become an increasingly used option for patients unable to conceive with autologous oocytes. In donor egg, the unique separation of the oocyte source and recipient uterus has created a model that has propelled advances in ART. Progressive ART innovations that have optimized the oocyte donor and resulting embryo include the following: evaluation of ovarian reserve, controlled ovarian hyperstimulation regimens that reduce the risk of ovarian hyperstimulation syndrome, blastocyst culture, oocyte cryopreservation, and preimplantation genetic testing. For donor egg recipients, methods to optimize the endometrium to maximize implantation include endometrial receptivity testing, immunologic donor-recipient matching, and increased understanding of the uterine microbiome. Innovations in assisted reproductive technologies (ART) have driven progress in the donor egg field since the birth of the first baby derived from a donor egg in 1983. Over time, donor oocytes have become an increasingly used option for patients unable to conceive with autologous oocytes. In donor egg, the unique separation of the oocyte source and recipient uterus has created a model that has propelled advances in ART. Progressive ART innovations that have optimized the oocyte donor and resulting embryo include the following: evaluation of ovarian reserve, controlled ovarian hyperstimulation regimens that reduce the risk of ovarian hyperstimulation syndrome, blastocyst culture, oocyte cryopreservation, and preimplantation genetic testing. For donor egg recipients, methods to optimize the endometrium to maximize implantation include endometrial receptivity testing, immunologic donor-recipient matching, and increased understanding of the uterine microbiome. Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/users/16110-fertility-and-sterility/posts/39242-27049 Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/users/16110-fertility-and-sterility/posts/39242-27049 Since the birth of the first baby from IVF 40 years ago, innovations in assisted reproductive technologies (ART) have driven progress in the donor egg field. Long gone are the days when donors were at high risk for ovarian hyperstimulation syndrome (OHSS), recipients were waiting months to find a donor, and clinics were struggling to perfectly synchronize donor and recipient cycles. This is fortunate as donor oocytes have become an increasingly used option for patients unable to conceive with autologous oocytes (1Kawwass J.F. Monsour M. Crawford S. Kissin D.M. Session D.R. Kulkarni A.D. et al.Trends and outcomes for donor oocyte cycles in the United States, 2000–2010.JAMA. 2013; 310: 2426-2434PubMed Google Scholar). Indeed, in an interview in which he discussed advances in ART, Dr. Howard Jones had this no-nonsense advice for the woman of advanced age contemplating pregnancy: "If she is comfortable with donor egg, I would think she would be well advised to expend her emotional and financial resources in a donor egg" (2Sontag S. Chat transcript: US father of IVF—Howard Jones, M.D. International Council on Infertility Information Dissemination, 2018Google Scholar). In addition to addressing a variety of reproductive problems, the introduction of human egg donation in 1983 has enhanced our understanding of the physiology and pathophysiology of human reproduction. These findings provide greater insight into possible predictors of live birth in donor oocyte cycles, allowing us to continue to improve outcomes moving forward. While increasing use of donor oocyte-recipient cycles has been due to optimization of ovarian stimulation in oocyte donors, as well as laboratory advances, the unique separation of the oocyte source and recipient uterus in donor egg has created a paradigm that has propelled advances in ART. This paper highlights advances in ART and the donor egg model that have impacted today's practice. We also identify future areas of innovation. Progressive ART innovations that have optimized the oocyte donor and resulting embryo include the following: evaluation of ovarian reserve, controlled ovarian hyperstimulation regimens that reduce risk of OHSS, blastocyst culture, oocyte cryopreservation, and preimplantation genetic testing. For donor egg recipients, methods to optimize the endometrium to maximize implantation include endometrial receptivity testing, immunologic donor-recipient matching, and increased understanding of the uterine microbiome. Early in the history of donor egg, oocytes were obtained primarily from women already undergoing IVF who had excess oocytes at the time of retrieval. Today, however, most egg donors are young women without infertility willing to donate their oocytes for altruistic or commercial reasons (3Morris R.S. Sauer M.V. New advances in the treatment of infertility in women with ovarian failure.Curr Opin Obstet Gynecol. 1993; 5: 368-377Crossref PubMed Scopus (24) Google Scholar). Along with donor age, ovarian reserve testing among prospective donors is useful to assess a donor's ovarian reserve status, predict ovarian response, and guide the stimulation protocol. Ultimately, success in oocyte donation cycles is dependent on both the recruitment and development of multiple follicles, leading to the development of multiple high-quality embryos for selection for ET. Indeed, in a retrospective cohort study of 237 fresh donor oocyte ET cycles, the greatest probability of live birth was observed in cycles with more oocytes retrieved (>10), more mature oocytes, and an increased number of cleavage stage embryos (4Hariton E. Kim K. Mumford S.L. Palmor M. Bortoletto P. Cardozo E.R. et al.Total number of oocytes and zygotes are predictive of live birth pregnancy in fresh donor oocyte in vitro fertilization cycles.Fertil Steril. 2017; 108: 262-268Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar). Developments in ART that have improved donor selection include the ovarian reserve markers antimüllerian hormone (AMH), baseline gonadotropin levels, and antral follicle count (AFC). In IVF cycles, AMH has been recognized as an accurate predictor of ovarian response to gonadotropin stimulation. Several studies have demonstrated significant correlations between AMH and donor response to controlled ovarian hyperstimulation. Specifically, we have learned that AMH can be correlated to number of oocytes retrieved, peak E2 levels, and the need for a decreased gonadotropin dose to avoid OHSS (5Nakhuda G.S. Douglas N.C. Thornton M.H. Guarnaccia M.M. Lobo R. Sauer M.V. Anti-Mullerian hormone testing is useful for individualization of stimulation protocols in oocyte donors.Reprod Biomed Online. 2011; 22: S88-S93Abstract Full Text PDF PubMed Scopus (7) Google Scholar). While one cross-sectional study demonstrated that AMH was superior to basal FSH in predicting low and high response in oocyte donors, it was also not predictive of embryo morphology or pregnancy outcome among recipients (6Riggs R. Kimble T. Oehninger S. Bocca S. Zhao Y. Leader B. et al.Anti-Mullerian hormone serum levels predict response to controlled ovarian hyperstimulation but not embryo quality or pregnancy outcome in oocyte donation.Fertil Steril. 2011; 95: 410-412Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar). In a prospective study of 1,075 oocyte donors, those with an AFC < 10 reported significantly lower E2 levels and fewer mature retrieved oocyte numbers. These donors also showed significantly higher cancellation and no-donation rates (7Melo M.A. Garrido N. Alvarez C. Bellver J. Meseguer M. Pellicer A. et al.Antral follicle count (AFC) can be used in the prediction of ovarian response but cannot predict the oocyte/embryo quality or the in vitro fertilization outcome in an egg donation program.Fertil Steril. 2009; 91: 148-156Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar). Of note, baseline FSH appears less predictive of other ovarian reserve measurements for the young donor egg population (8Esposito M.A. Coutifaris C. Barnhart K.T. A moderately elevated day 3 FSH concentration has limited predictive value, especially in younger women.Hum Reprod. 2002; 17: 118-123Crossref PubMed Scopus (87) Google Scholar). As donor egg use increased and young donors were recruited, it was critical to develop a suitable stimulation protocol for a group of fertile young women at risk for developing OHSS. Both the development of antagonist protocols and use of GnRH agonist triggers were critical ART innovations that optimized oocyte yield while minimizing risks to donors. In the late 1980s, the standard of care in autologous IVF cycles was suppression of the hypothalamic-pituitary axis using GnRH agonists to prevent a premature LH surge. This approach optimized autologous IVF outcomes and likewise became the typical protocol for oocyte donor cycles (9Klein J. Sauer M.V. Oocyte donation.Best Pract Res Clin Obstet Gynaecol. 2002; 16: 277-291Crossref PubMed Scopus (45) Google Scholar, 10Sauer M.V. Oocyte donation: reflections on past work and future directions.Hum Reprod. 1996; 11: 1149-1150Crossref PubMed Scopus (24) Google Scholar). GnRH antagonist protocols were introduced into clinical practice in the late 1990s and have emerged as the standard protocol for contemporary oocyte donor IVF cycles due to multiple benefits. They offer the advantage of fewer injections for the donor, fewer days of medication, and a decreased risk of OHSS (11A double-blind, randomized, dose-finding study to assess the efficacy of the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462) to prevent premature luteinizing hormone surges in women undergoing ovarian stimulation with recombinant follicle stimulating hormone (Puregon). The Ganirelix Dose-Finding Study Group.Hum Reprod. 1998; 13: 3023-3031Crossref PubMed Scopus (337) Google Scholar, 12de Jong D. Macklon N.S. Mannaerts B.M. Coelingh Bennink H.J. Fauser B.C. High dose gonadotrophin-releasing hormone antagonist (ganirelix) may prevent ovarian hyperstimulation syndrome caused by ovarian stimulation for in-vitro fertilization.Hum Reprod. 1998; 13: 573-575Crossref PubMed Scopus (50) Google Scholar). Oocyte donation studies have failed to demonstrate a negative impact of GnRH antagonists on oocyte or embryo quality compared with those treated with GnRH agonists (13Vlahos N.F. Bankowski B.J. Zacur H.A. Garcia J.E. Wallach E.E. Zhao Y. An oocyte donation protocol using the GnRH antagonist ganirelix acetate, does not compromise embryo quality and is associated with high pregnancy rates.Arch Gynecol Obstet. 2005; 272: 1-6Crossref PubMed Scopus (9) Google Scholar, 14Bodri D. Sunkara S.K. Coomarasamy A. Gonadotropin-releasing hormone agonists versus antagonists for controlled ovarian hyperstimulation in oocyte donors: a systematic review and meta-analysis.Fertil Steril. 2011; 95: 164-169Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar). The donor egg model was used to specifically compare agonist and antagonist protocols. A prospective randomized study demonstrated that the antagonist protocol was equivalent to the long agonist protocol with respect to clinical pregnancy, implantation, and miscarriage rate in oocyte donor cycles (15Prapas N. Prapas Y. Panagiotidis Y. Prapa S. Vanderzwalmen P. Schoysman R. et al.GnRH agonist versus GnRH antagonist in oocyte donation cycles: a prospective randomized study.Hum Reprod. 2005; 20: 1516-1520Crossref PubMed Scopus (52) Google Scholar). In a subsequent randomized trial, oocyte donors underwent controlled ovarian hyperstimulation with either a GnRH agonist or antagonist protocol. Further demonstrating the efficacy of antagonist cycles in this group, the study team found no significant difference in number of mature oocytes retrieved or pregnancy rates between donors undergoing controlled ovarian hyperstimulation with GnRH antagonist or short GnRH agonist protocols (16Bodri D. Vernaeve V. Guillen J.J. Vidal R. Figueras F. Coll O. Comparison between a GnRH antagonist and a GnRH agonist flare-up protocol in oocyte donors: a randomized clinical trial.Hum Reprod. 2006; 21: 2246-2251Crossref PubMed Scopus (31) Google Scholar). A follow-up systematic review and meta-analysis reported similar ongoing pregnancy rates for GnRH agonist and antagonist protocols. While the duration of stimulation was lower with the GnRH antagonist protocol, no significant differences were observed in the number of oocytes retrieved, gonadotropin consumption, or OHSS incidence. A Cochrane review also suggested similar clinical outcomes using either GnRH agonist or antagonist cycles in donor oocyte cycles, providing clinicians reassurance for using either option without compromising results (17Al-Inany H.G. Youssef M.A. Aboulghar M. Broekmans F. Sterrenburg M. Smit J. et al.Gonadotrophin-releasing hormone antagonists for assisted reproductive technology.Cochrane Database Syst Rev. 2011; : CD001750Google Scholar). With the advent of GnRH antagonist protocols, use of a GnRH agonist trigger to prevent OHSS was recognized and rapidly used. Stories of the early days of donor egg before the use of GnRH agonist triggers, when severe OHSS was a devastating consequence of controlled ovarian hyperstimulation, build upon our appreciation of this advance in ART. Much of the data regarding GnRH agonist trigger to decrease risk of OHSS, while not impacting oocyte yield and embryo development, were demonstrated in the oocyte donor model. Several retrospective studies and randomized clinical trials were performed in oocyte donors, showing a significantly reduced OHSS incidence when a GnRH agonist was used for inducing final oocyte maturation instead of hCG (18Bodri D. Guillen J.J. Trullenque M. Schwenn K. Esteve C. Coll O. Early ovarian hyperstimulation syndrome is completely prevented by gonadotropin releasing-hormone agonist triggering in high-risk oocyte donor cycles: a prospective, luteal-phase follow-up study.Fertil Steril. 2010; 93: 2418-2420Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, 19Hernandez E.R. Gomez-Palomares J.L. Ricciarelli E. No room for cancellation, coasting, or ovarian hyperstimulation syndrome in oocyte donation cycles.Fertil Steril. 2009; 91: 1358-1361Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar, 20Galindo A. Bodri D. Guillen J.J. Colodron M. Vernaeve V. Coll O. Triggering with HCG or GnRH agonist in GnRH antagonist treated oocyte donation cycles: a randomised clinical trial.Gynecol Endocrinol. 2009; 25: 60-66Crossref PubMed Scopus (72) Google Scholar, 21Melo M. Busso C.E. Bellver J. Alama P. Garrido N. Meseguer M. et al.GnRH agonist versus recombinant HCG in an oocyte donation programme: a randomized, prospective, controlled, assessor-blind study.Reprod Biomed Online. 2009; 19: 486-492Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar, 22Acevedo B. Gomez-Palomares J.L. Ricciarelli E. Hernandez E.R. Triggering ovulation with gonadotropin-releasing hormone agonists does not compromise embryo implantation rates.Fertil Steril. 2006; 86: 1682-1687Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar). A retrospective analysis of 1,171 oocyte donors undergoing 2,077 stimulation cycles reported recipient outcome was not significantly different when comparing oocytes from GnRH antagonist donor cycles triggered with either hCG or GnRH agonist. Additionally, GnRH agonist triggering was associated with a lower incidence of moderate/severe OHSS in egg donors (23Bodri D. Guillen J.J. Galindo A. Mataro D. Pujol A. Coll O. Triggering with human chorionic gonadotropin or a gonadotropin-releasing hormone agonist in gonadotropin-releasing hormone antagonist-treated oocyte donor cycles: findings of a large retrospective cohort study.Fertil Steril. 2009; 91: 365-371Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar). In addition to preventing OHSS, GnRH agonist triggers were shown in a number of retrospective and prospective studies in oocyte donors to not negatively impact oocyte yield, embryo quality, or recipient pregnancy rates (24Erb T.M. Vitek W. Wakim A.N. Gonadotropin-releasing hormone agonist or human chorionic gonadotropin for final oocyte maturation in an oocyte donor program.Fertil Steril. 2010; 93: 374-378Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar, 25Sismanoglu A. Tekin H.I. Erden H.F. Ciray N.H. Ulug U. Bahceci M. Ovulation triggering with GnRH agonist vs. hCG in the same egg donor population undergoing donor oocyte cycles with GnRH antagonist: a prospective randomized cross-over trial.J Assist Reprod Genet. 2009; 26: 251-256Crossref PubMed Scopus (59) Google Scholar). Likewise, in a randomized study comparing GnRH agonist or recombinant hCG triggers, there was no difference in oocyte morphology, embryo quality, implantation, or pregnancy rates, while OHSS was reduced, in donors who received a GnRH agonist trigger (22Acevedo B. Gomez-Palomares J.L. Ricciarelli E. Hernandez E.R. Triggering ovulation with gonadotropin-releasing hormone agonists does not compromise embryo implantation rates.Fertil Steril. 2006; 86: 1682-1687Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar). A randomized controlled trial of 212 oocyte donors who received either GnRH or hCG trigger found no difference in the number of mature oocytes retrieved or pregnancy rates. However, there were significantly more cases of OHSS in patient who received the hCG trigger (20Galindo A. Bodri D. Guillen J.J. Colodron M. Vernaeve V. Coll O. Triggering with HCG or GnRH agonist in GnRH antagonist treated oocyte donation cycles: a randomised clinical trial.Gynecol Endocrinol. 2009; 25: 60-66Crossref PubMed Scopus (72) Google Scholar). Compared with stories from early donor egg when recipients waited several months to even a year for a suitable donor to become available, today in many countries such as the U.S. a recipient can simply browse a donor egg bank website for a suitable donor and purchase a cohort of frozen eggs online, allowing delivery within days. Indeed, improvements in oocyte cryopreservation techniques, specifically vitrification, advanced the status of oocyte cryopreservation such that it was deemed no longer experimental in 2012 (26Practice Committees of American Society for Reproductive Medicine, Society for Assisted Reproductive TechnologyMature oocyte cryopreservation: a guideline.Fertil Steril. 2013; 99: 37-43Abstract Full Text Full Text PDF PubMed Scopus (680) Google Scholar). Subsequently, cryopreserved donor oocyte banks expanded in availability, improving access and lowering donor egg costs (27Kushnir V.A. Gleicher N. Fresh versus cryopreserved oocyte donation.Curr Opin Endocrinol Diabetes Obes. 2016; 23: 451-457Crossref PubMed Scopus (9) Google Scholar). Based on early reports that IVF outcomes with cryopreserved and fresh donor oocytes are comparable (28Cobo A. Meseguer M. Remohi J. Pellicer A. Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial.Hum Reprod. 2010; 25: 2239-2246Crossref PubMed Scopus (416) Google Scholar), frozen donor egg banks have emerged as an alternative for patients over using a fresh donor. Benefits of oocyte cryopreservation include simplified IVF logistics since coordinating donor and recipient cycles is no longer necessary, reduced costs, and a faster flow as donors can be selected from a bank and used relatively quickly (27Kushnir V.A. Gleicher N. Fresh versus cryopreserved oocyte donation.Curr Opin Endocrinol Diabetes Obes. 2016; 23: 451-457Crossref PubMed Scopus (9) Google Scholar). Before the experimental label for oocyte cryopreservation was lifted, it was actually early work with frozen donor oocytes that demonstrated improved efficiency of vitrified oocytes over the traditional slow-freezing method. In 2009, a report of 153 vitrified oocytes from 10 donors demonstrated the promise of this technology with 87.6% oocyte survival post-thaw, 87.3% fertilization, 68% blastocyst development, and a 75% pregnancy rate per transfer (29Nagy Z.P. Chang C.C. Shapiro D.B. Bernal D.P. Elsner C.W. Mitchell-Leef D. et al.Clinical evaluation of the efficiency of an oocyte donation program using egg cryo-banking.Fertil Steril. 2009; 92: 520-526Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar). In a large randomized controlled trial of 600 recipients randomized to fresh versus frozen donor oocytes, recipients using either vitrified or fresh oocytes were similar with respect to clinical pregnancy rate per cycle (50.2 vs. 49.8%; P=.933) and clinical pregnancy rate per ET (55.4 vs. 55.6%; P=.974) (28Cobo A. Meseguer M. Remohi J. Pellicer A. Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial.Hum Reprod. 2010; 25: 2239-2246Crossref PubMed Scopus (416) Google Scholar). More recently, several studies have demonstrated positive outcomes with comparable blastocyst development between fresh and vitrified sibling oocytes (30Rienzi L. Romano S. Albricci L. Maggiulli R. Capalbo A. Baroni E. et al.Embryo development of fresh "versus" vitrified metaphase II oocytes after ICSI: a prospective randomized sibling-oocyte study.Hum Reprod. 2010; 25: 66-73Crossref PubMed Scopus (363) Google Scholar, 31Cobo A. Kuwayama M. Perez S. Ruiz A. Pellicer A. Remohi J. Comparison of concomitant outcome achieved with fresh and cryopreserved donor oocytes vitrified by the Cryotop method.Fertil Steril. 2008; 89: 1657-1664Abstract Full Text Full Text PDF PubMed Scopus (434) Google Scholar) and similar implantation and clinical pregnancy rates using fresh or vitrified oocytes in oocyte donor recipients (28Cobo A. Meseguer M. Remohi J. Pellicer A. Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial.Hum Reprod. 2010; 25: 2239-2246Crossref PubMed Scopus (416) Google Scholar, 29Nagy Z.P. Chang C.C. Shapiro D.B. Bernal D.P. Elsner C.W. Mitchell-Leef D. et al.Clinical evaluation of the efficiency of an oocyte donation program using egg cryo-banking.Fertil Steril. 2009; 92: 520-526Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar). This is in contrast to a large 2013 study that reported on 11,148 donor oocyte cycles in the United States, of which 20% used cryopreserved oocytes. Per ET, live birth rates were 56.1% with fresh oocytes versus 47.1% with cryopreserved oocytes (difference, 9.0%; 95% confidence interval [CI], 6.6%–11.4%; P<.001) (32Kushnir V.A. Barad D.H. Albertini D.F. Darmon S.K. Gleicher N. Outcomes of fresh and cryopreserved oocyte donation.JAMA. 2015; 314: 623-624Crossref PubMed Scopus (23) Google Scholar). Likewise, in a retrospective cohort study from the National ART Surveillance System, the team evaluated 105,517 fresh embryo cycles initiated in 2013 in the United States using embryos created with both fresh and cryopreserved oocytes from both autologous and donor cycles. Donor cryopreserved oocyte cycles had a decreased likelihood of pregnancy (relative risk = 0.88; 95% CI, 0.81–0.95) and live birth (relative risk = 0.87; 95% CI, 0.80–0.95). For cycles proceeding to transfer, there was no evidence of differences in implantation, pregnancy, or live birth rates (33Crawford S. Boulet S.L. Kawwass J.F. Jamieson D.J. Kissin D.M. Cryopreserved oocyte versus fresh oocyte assisted reproductive technology cycles, United States, 2013.Fertil Steril. 2017; 107: 110-118Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar). Currently, the convenience and decreased costs of vitrified donor eggs must be balanced with potentially lower pregnancy rates per egg. However, additional studies evaluating recent vitrification outcomes are needed as prior reports may include slow-freezing outcomes and earlier techniques. The clinical practice shift to widespread blastocyst transfer, including in oocyte donor recipients, represents a key factor in improving ART outcomes. Advances in highly specific sequential and nonsequential embryo culture systems have resulted in successful development of embryos to the blastocyst stage (34Gardner D.K. Lane M. Schoolcraft W.B. Culture and transfer of viable blastocysts: a feasible proposition for human IVF.Hum Reprod. 2000; 15: 9-23PubMed Google Scholar). This has resulted in the evolution of blastocyst ET for donor egg recipients as well as the ability to cryopreserve embryos at the blastocyst stage. Numerous prospective randomized trials have compared cleavage-stage with blastocyst ET, most of which demonstrated improved outcomes with blastocyst transfer (35Coskun S. Hollanders J. Al-Hassan S. Al-Sufyan H. Al-Mayman H. Jaroudi K. Day 5 versus day 3 embryo transfer: a controlled randomized trial.Hum Reprod. 2000; 15: 1947-1952Crossref PubMed Scopus (191) Google Scholar, 36Van der Auwera I. Debrock S. Spiessens C. Afschrift H. Bakelants E. Meuleman C. et al.A prospective randomized study: day 2 versus day 5 embryo transfer.Hum Reprod. 2002; 17: 1507-1512Crossref PubMed Scopus (101) Google Scholar, 37Levron J. Shulman A. Bider D. Seidman D. Levin T. Dor J. A prospective randomized study comparing day 3 with blastocyst-stage embryo transfer.Fertil Steril. 2002; 77: 1300-1301Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar). In a retrospective series of 229 patients undergoing oocyte donation, 116 underwent day 3 transfer and 113 underwent day 5 transfer. Clinical pregnancy rates per retrieval were significantly higher with blastocyst transfer (87.6% vs. 75.0%; P<.05) (33Crawford S. Boulet S.L. Kawwass J.F. Jamieson D.J. Kissin D.M. Cryopreserved oocyte versus fresh oocyte assisted reproductive technology cycles, United States, 2013.Fertil Steril. 2017; 107: 110-118Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar). Likewise, in a retrospective study comparing cleavage and blastocyst ET in 93 consecutive oocyte donation cycles, significantly higher clinical pregnancy rates (73% vs. 40%; P<.01) were obtained after blastocyst transfers (35Coskun S. Hollanders J. Al-Hassan S. Al-Sufyan H. Al-Mayman H. Jaroudi K. Day 5 versus day 3 embryo transfer: a controlled randomized trial.Hum Reprod. 2000; 15: 1947-1952Crossref PubMed Scopus (191) Google Scholar). With these advances, an emerging need to maximize the likelihood of a live birth while minimizing the risk of multiple gestations has attained paramount importance, particularly for oocyte donation. Guidelines from the American Society for Reproductive Medicine have stated that in the case of young oocyte donors, only a single blastocyst-stage or no more than two cleavage-stage embryos may be transferred (38Practice Committee of the American Society for Reproductive Medicine, Practice Committee of the Society for Assisted Reproductive TechnologyGuidance on the limits to the number of embryos to transfer: a committee opinion.Fertil Steril. 2017; 107: 901-903Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar). Despite these recommendations, single blastocyst ET for donor oocyte recipients does not appear to be widely used. In an analysis of over 10,695 donor oocyte cycles in the United States from 2013–14, only 34.5% of donor oocyte cycles transferred one single blastocyst embryo. While live birth rates for single blastocyst transfer versus double ET were mildly increased for double ET (54.6% vs. 62.0%; P<.0001), the multiple pregnancy rate was significantly higher for double ET (1.3% vs. 47.9%; P<.0001) (39Klenov V.E. Boulet S.L. Mejia R.B. Kissin D.M. Munch E. Mancuso A. et al.Live birth and multiple birth rates in US in vitro fertilization treatment using donor oocytes: a comparison of single-embryo transfer and double-embryo transfer.J Assist Reprod Genet. 2018; https://doi.org/10.1007/s10815-018-1243-0Crossref Scopus (7) Google Scholar). In a retrospective analysis of 13,393 donor-recipient cycles from 2011 to 2012 in the United States, only 28% of blastocyst transfer cycles were compliant with guidelines to transfer one blastocyst embryo when the donor was < 35 year old. The multiple pregnancy rate was significantly higher in the noncompliant blastocyst cohort at 53% (compared with 2% in compliant cycles) (40Acharya K.S. Keyhan S. Acharya C.R. Yeh J.S. Provost M.P. Goldfarb J.M. et al.Do donor oocyte cycles comply with ASRM/SART embryo transfer guidelines? An analysis of 13,393 donor cycles from the SART registry.Fertil Steril. 2016; 106: 603-607Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar). There is no doubt that preimplantation genetic testing for aneuploidy (PGT-A) has revolutionized ART and will continue to expand in the future. The full impact and utility of PGT-A on donor oocyte cycles is still unclear. Historically, egg donor cycles have resulted in transfer of PGT-untested embryos. While donor oocyte cycles typically result in high pregnancy and live birth rates due to the young age of the donor, prior studies have shown that up to one third of embryos derived from donor oocytes are aneuploid (41Haddad G. Deng M. Wang C.T. Witz C. Williams D. Griffith J. et al.Assessment of aneuploidy formation in human blastocysts resulting from donated eggs and the necessity of the embryos for aneuploidy screening.J Assist Reprod Genet. 2015; 32: 999-1006Crossref PubMed Scopus (27) Google Scholar, 42Munne S. Ary J. Zouves C. Escudero T. Barnes F. Cinioglu C. et al.Wide range of chromosome abnormalities in the embryos of young egg donors.Reprod Biomed Online. 2006; 12: 340-346Abstract Full Text PDF PubMed Google Scholar). In a retrospective cross-sectional