Obstetrical and Neonatal Outcomes From the BEST Trial

Abstract

Although transfer of multiple embryos improves the likelihood for a delivery after each in vitro fertilization (IVF) cycle, it carries a significant risk for increased maternal and neonatal morbidity associated with multiple births. Early attempts to detect aneuploidy in cleavage-stage embryos and transfer only euploid embryos did not improve delivery rates, most likely because of a negative impact of cleavage-stage biopsy and the poor accuracy of fluorescence in situ hybridization for detection of aneuploidy. In recent years, improved delivery rates have been demonstrated with the use of blastocyst-stage biopsies and more accurate preimplantation genetic diagnosis such as real-time quantitative polymerase chain reaction. Nearly all deliveries after elective single-embryo transfer (eSET) are singletons. The Blastocyst Euploid Selective Transfer (BEST) Trial was a randomized, noninferiority study that compared the use of eSET after real-time quantitative polymerase chain reaction–based comprehensive chromosome screening with transfer of 2 untested (unselected) embryos. Initial data from that trial were previously published. The aim of the present study was to determine whether eSET after trophectoderm biopsy and rapid aneuploidy screening would improve the chance for a healthy term, singleton delivery compared with transferring 2 untested embryos. Infertile couples with a female partner up to 42 years old undergoing IVF were enrolled. A total of 175 patients were randomized to either the euploid eSET group (n = 89) or the untested 2-embryo transfer group (did not undergo biopsy for aneuploidy screening; n = 86). The Mann-Whitney U test was used to compare birth weight, gestational age at delivery, and length of stay in the neonatal intensive care unit (NICU). The χ2 test was used to compare the risk for preterm delivery (<37 weeks), low birth weight (<2500 g), and NICU admission. Although cumulative delivery rates were similar in the groups through the fresh cycle and up to 1 frozen transfer (69% in the euploid eSET group vs 72% in the untested 2-embryo transfer group; P = 0.6), there was a marked difference in multiple births (1.6% in the euploid eSET group vs 47% in the untested 2-embryo transfer group; P = 0.0001). As expected, the risks for preterm delivery, low birth weight, and NICU admission were significantly higher after untested 2-embryo transfer (P < 0.05 for all comparisons). Moreover, babies in the untested 2-embryo transfer group spent 5 times as many days in the NICU (479 vs 93 days; P = 0.03). Enhanced embryo selection using a validated method of aneuploidy screening allows selective transfer of a single euploid embryo with high reproductive potential. With this approach, the risk for multizygotic multiple gestation is eliminated and the chance of having a healthy, term singleton delivery after IVF is improved without compromising delivery rates.