Obstetrical and Neonatal Outcomes From the BEST Trial

Abstract

Nearly 50% of all US babies born after in vitro fertilization are multiple gestations. Because nearly all deliveries after elective single-embryo transfer (eSET) are singletons, the authors hypothesized that obstetrical and neonatal outcomes could be improved in patients randomized to euploid eSET compared with those undergoing transfer of 2 untested embryos. The Blastocyst Euploid Selective Transfer (BEST) trial was a randomized, noninferiority study comparing SET after real-time quantitative polymerase chain reaction–based comprehensive chromosome screening with transfer of 2 untested embryos. When at least 2 embryos reached the blastocyst stage of development, patients were randomized to the screened euploid eSET or untested 2-embryo transfer group. The primary outcome was the ongoing pregnancy rate to a viable gestation after the first embryo transfer, fresh or frozen. This current study is an analysis of the final obstetrical and neonatal delivery outcomes of patients randomized in the earlier trial after the initial fresh cycle and up to 1 frozen transfer. Patients provided data on gestational age at delivery, mode of delivery, birth weight, sex, pregnancy complications, and number of days their newborns were in the neonatal intensive care unit (NICU). Eighty-nine and 86 patients were randomized to the euploid eSET and untested 2-embryo transfer group, respectively. The 2 groups were similar in all demographic characteristics; the mean (SD) ages were 35.1 (3.9) and 34.5 (4.7) years (P = 0.5), respectively. The mean number of blastocysts suitable for transfer was 5.8 (range, 2–22) for eSET and 5.3 (range, 2–18) for 2-embryo transfer. In the eSET group, a biopsy of 521 blastocysts was performed for comprehensive chromosome screening, with an aneuploidy rate of 31% (n = 162). The proportion of aneuploid embryos increased with increasing age (21%, 34%, 56%, and 56% for ages <35 years, 35–37 years, 38–40 years, and 41–42 years, respectively; P < 0.001). The cumulative delivery rate after up to 1 frozen transfer was 69% after eSET and 72% after 2-embryo transfer (P = 0.6). Interestingly, 58% of the transferred embryos resulted in live births after eSET of genetically screened embryos; and 46%, after 2-embryo transfer of untested embryos (P = 0.048). Rates of multiple deliveries were 47% in the 2-embryo transfer group and 1.6% in the eSET group (relative risk [RR], 28.5; 95% confidence interval, 4.01–202.9). Per patient randomized, the chance of having a term singleton delivery was 60% after eSET and 31% after 2-embryo transfer (P < 0.001). The risk for preterm delivery was 29% after 2-embryo transfer and 13% for eSET (RR, 2.21; 95% confidence interval, 1.04–4.70; P = 0.03). The risk for a newborn being less than 2500 g was 11% in the eSET group and 33% in the 2-embryo transfer group (P = 0.002). The risk for a newborn being admitted to the NICU was 26% and 11% in the 2-embryo transfer and eSET group, respectively (P = 0.04). Culturing embryos to the blastocyst stage, performing a trophectoderm biopsy, and amplifying DNA with quantitative polymerase chain reaction assays on each chromosome will allow selection of a single euploid blastocyst with high reproductive potential. This strategy dramatically reduces the risk for multiple gestation and increases the chance for a healthy, term singleton delivery without requiring patients to undergo many failed cycles. The improved obstetrical and neonatal outcomes suggest that this approach may become the standard of care for couples requiring in vitro fertilization.