Risks of neonatal anomalies and obstetric complications in 7378 singleton births after frozen–thawed and fresh embryo transfers in Japan: An analysis using doubly robust estimation

Abstract

Purpose: To compare risks of neonatal anomalies and obstetric complications among frozen–thawed embryo transfer (FET), fresh embryo transfer (FreshET), and non-assisted reproductive technology (non-ART) treatments in infertile women. Methods: This retrospective cohort study analyzed 7378 singleton births (2643 non-ART, 4219 FET, 516 FreshET) from 2013 to 2022. Outcomes were compared using inverse probability weighting regression adjustment, with adjustment for maternal factors. Results: After adjustment, the risk of neonatal anomalies did not differ significantly between FET and non-ART, or FreshET and non-ART. FET was associated with increased risks of obstetric complications compared with non-ART, including placenta accreta (adjusted risk difference [ARD] 3.61%, 95% CI 2.95–4.28), placenta previa (ARD 0.55%, 95% CI 0.14–0.96), postpartum hemorrhage (ARD 7.08%, 95% CI 6.03–8.13), gestational hypertension (ARD 3.57%, 95% CI 2.47–4.68), gestational diabetes (ARD 0.96%, 95% CI 0.17–1.75), and preterm birth (ARD 2.13%, 95% CI 1.23–3.02). FET also showed higher risk of high birth weight (ARD 0.97%, 95% CI 0.42–1.52). FreshET showed no significant differences in obstetric complications. Conclusions: While the risk of neonatal anomalies did not differ among treatments, FET was associated with increased obstetric complication risks. These findings underscore the need for careful management of FET pregnancies and further research to improve treatment protocols.