Two’s company, three’s a crowd: involvement of a gestational carrier necessitates use of best and safe practices

Abstract

As reproductive endocrinologists, this setting is all too familiar: navigating the difficult conversation between the intended parent(s) (IP) and gestational carrier (GC) of the number of embryos to transfer. We all know it is not uncommon to find them in agreement and pleading for the transfer of two good quality blastocysts, sometimes even two euploid blastocysts after preimplantation genetic testing (PGT-A), to increase the odds of a successful pregnancy. The reproductive attorney has written into the executed contract between both parties that one versus two embryos is acceptable. The GC is healthy and has carried to term in the past and only wishes to have one more pregnancy. The IP ideally wants two children and cannot afford this process again. Truth be told, the IP actually hopes for what we plan to discuss as an adverse outcome of transferring two embryos: a multiple gestation. Namath et al. (1Namath A. Jahandideh S. Devine K. O’Brien J. Stillman R. Gestational carrier pregnancy outcomes from frozen embryo transfer depending on the number of embryos transferred and pre-implantation genetic testing: a retrospective analysis.Fertil Steril. 2021; 115: 1471-1477Abstract Full Text Full Text PDF Scopus (1) Google Scholar) address this important and complex topic in their retrospective cohort study covering nearly a decade of frozen embryo transfer cycles involving a GC. It is important for readers to understand the data analyzed: 583 total cycles of which 427 were single embryo transfers (SET) and of those, 194 used PGT-A. The majority of the cycles respectfully used SET and very few PGT-A cases were double embryo transfers (DET). The data are presented as outcomes of SET versus DET, which can be hard to interpret at times when trying to differentiate how much of the negative outcomes are truly a result of a twin gestation rather than an adverse outcome in a singleton live birth after DET to start (it is unclear if any were early twin gestations with spontaneous reduction to singleton). One primary conclusion of the study was that live births (LB) resulting from DET showed higher risk of preterm birth (PTB) and lower birth rates compared with LB resulting from SET. Based on the data of the study, when one truly analyzes only singleton LB from DET versus SET, the difference in mean gestational age was 37.35 versus 37.98 weeks, respectively, and the difference in birth weight is 237 gm. Deciding if such an absolute difference is clinically relevant outside of the multiple embryo transfer discussion is too difficult to determine and the study is likely underpowered to make this conclusion. Overall, the primary outcomes of the study confirm much of what we already know and the reasons behind the general trend that we have seen in our field over the past decade toward elective SET – transferring >1 high quality blastocyst significantly increases the rate of multiple pregnancy, increasing the rate of PTB associated with a multiple gestation. The study found that there was a 10-fold higher chance of a multiple birth if two embryos were transferred instead of one (20% vs. 2%). Fortunately, no triplet pregnancies were reported in this cohort. If PGT-A–tested embryos were used for a DET, the rate of multiples increased even further to 35%, but the study only had 31 cycles in which two euploid embryos were transferred. Approximately 40% of DETs resulted in PTB which is to be expected in twin gestations and is less than what often is reported by the Centers for Disease Control in the United States in multiple gestations, which can be upwards of 60% (2Martin J.A. Osterman M.J.K. Describing the increase in preterm births in the United States, 2014-2016.NCHS Data Brief. 2018; 312: 1-8Google Scholar). However, it is fairly reassuring that the majority were late PTB as the mean gestational age was 36.3 ± 3 weeks in the DET group. No specific neonatal outcomes or hospital stay details were collected. Study results also demonstrated a significantly higher live birth rate (LBR) if two embryos were transferred (51.3% vs. 36.8%). This LBR number is what patients often hear first and foremost, because after all that the IP has experienced, what is most important to them is how to best optimize the chances of having a take home baby. The conclusions of the study are sound, but not necessarily novel in that they emphasize what we already know, that is DETs increase LBR but are associated with greater neonatal, maternal, and obstetric risks. The LBR difference seen between the SET and DET group in this study is expectedly higher than what has been reported in non-GC cycles, likely because of the optimal uterine environment of a GC. What this study does nicely elucidate is lacking data on GC outcomes in the United States, especially from centers with standardized protocols and respectable success rates. The data presented showed that their success rates continued to rise in SET, especially in the last couple of years, which is particularly reassuring and shows that we are making strides to attain the singleton success rates we all strive to achieve. However, we would caution the wording in this publication just slightly. The investigators note that their subanalysis of the PGT-A selected cycles showed no difference in LBR between the PGT-A and non-PGT-A cycles (41.2 % vs. 43.7%). This study is underpowered to draw any conclusions on PGT-A cycle outcomes. One also must consider all of the changes seen in PGT-A techniques over the years as well as the increasing use of PGT-A since the time at which these data were drawn from, which both are potential contributing factors. The investigators note that the LBR was the highest with a double embryo transfer of PGT-A–tested embryos (64.5%). Again, the study was underpowered to determine any conclusions and this LBR must be used with caution when counseling patients, so as not to encourage more frequent double euploid embryo transfers. One also should be wary of drawing conclusions from data in which the cycles are not all independent variables or observations. In cases where individual patients contribute >1 cycle to the data, most statisticians will argue the need for more complex analyses since these are no longer independent variables. It is difficult to determine how many GC cycles were from the same GC in this publication as this is not shared. The average gravidity is 4 and, put simply, if one particular GC carried two or three pregnancies but had smaller birthweight children, she would contribute more to the outcome, as those are not independent pregnancies. Some could question the validity of the conclusions and, while this is more of a teaching point for readers, it is important to consider. While the conclusions are not necessarily novel, the study brings us back to the core of what we all should believe: our job as reproductive endocrinologists is to provide the best and safest outcome for the IP, GC, and future children in accordance with Food and Drug Administration and American Society for Reproductive Medicine guidelines and recommendations, which means optimizing a healthy singleton live birth whenever possible. Some in vitro fertilization centers do not allow DETs for GCs, particularly when the age of the oocyte source is young or PGT-A is used. Others favor more autonomy over paternalism. These cases are challenging and bring up a myriad of ethical and legal considerations. We have had and continue to have obvious and compelling neonatal and obstetrical data showing added significant risk with DETs. What we must remember though is that with GC cycles, another person’s wellness is now at stake and we must be focused on safety. Consideration of costs incurred for the patient is something that will never be eliminated from the equation when making decisions. If surrogacy was not so expensive and complicated, the answer would seem easier. These data highlight two much larger and critical concerns, one of which is how to improve access to care to remove the ethical, paternalistic, and financial factors that bring this discussion to light, as we all have a responsibility to optimize a singleton healthy live birth. Fortunately, the more recent improvements in laboratory and embryo culture techniques, PGT-A technologies, and knowledge around in vitro fertilization processes are increasing LBR, so patients are more comfortable with success rates using a single good quality blastocyst. Yet, it does not begin to solve the fertility treatment access to care concerns in the United States and globally, as many patients make decisions based on what is most cost effective for them, regardless of what may be most cost effective for healthcare. The second concern in this publication is the remaining 3.8% of extremely preterm birth cycles in predominantly twin gestations. These cases represent the largest risk of morbidity and mortality to neonates, the hardest emotional toll on the IP and, in reality, the largest financial impact on payors and society. So, this brings us back to the core question at hand, how do we continue to improve access to care so that this question is no longer a debate in GC and non-GC cycles? We challenge each of you to continue to search for solutions to these bigger concerns. Gestational carrier pregnancy outcomes from frozen embryo transfer depending on the number of embryos transferred and preimplantation genetic testing: a retrospective analysisFertility and SterilityVol. 115Issue 6PreviewTo compare gestational age, birth weight (BW), and live birth rates in gestational carriers (GC) after the transfer of 1 or 2 frozen embryo(s) with or without preimplantation genetic testing for aneuploidy (PGT-A), with the understanding that several social and economic factors may motivate intended parents to request the transfer of 2 embryos and/or PGT-A when using a GC. Full-Text PDF