Abstract
OBJECTIVE: To assess neonatal outcomes in siblings born after frozen embryo transfer (FET) in comparison with siblings born after fresh embryo transfer. DESIGN: Prospective cohort study. Linear mixed models and generalized linear mixed models were used to study the association between outcomes after FET vs. fresh embryo transfer, considering the correlation of observations from siblings and controlling for treatment and maternal characteristics. Subgroup analysis according to the day of fresh embryo transfer and according to the FET protocol was also performed. SUBJECTS: Sibling pairs of singletons born to mothers who had both fresh and vitrified embryos transferred between 2008 and 2021, irrespective of the order (fresh-frozen or frozen-fresh) from a single center were included. Sibling pairs born after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and after embryo biopsy were considered. EXPOSURE: Women who had singleton deliveries after both fresh (cleavage stage or blastocyst stage) and vitrified (cleavage stage or blastocyst stage) embryo transfers. MAIN OUTCOME MEASURES: Measurements at birth, as well as neonatal outcomes including prematurity, small-for-gestational age, large-for-gestational age (LGA), perinatal death and congenital malformations. RESULTS: Data were available for 1,185 sibling pairs born after IVF/ICSI and for 155 sibling pairs born after embryo biopsy. Higher mean birthweight standard deviation scores were found in FET siblings compared with siblings born after fresh embryo transfer, even after adjustment for treatment and maternal characteristics. This finding was confirmed in the subgroup analysis according to the day of fresh embryo transfer and according to the FET protocol. Frozen embryo transfer was associated with a lower risk of prematurity and a higher risk of LGA after adjustment for treatment and maternal characteristics. The rates of perinatal deaths and congenital malformations were comparable between siblings born after FET and fresh embryo transfer. Like the outcomes for IVF/ICSI sibling pairs, higher LGA rates and higher mean birthweight standard deviation scores were found for FET siblings born after embryo biopsy when compared with siblings born after fresh embryo transfer. CONCLUSION: Our results in siblings born after IVF/ICSI and after embryo biopsy, indicated that FET is associated with higher birthweight, even after controlling for confounders.