Neonatal outcomes following different ovarian stimulation protocols in fresh single embryo transfer

Previous studies suggested ovarian stimulation was associated with lower birth weight and higher risk of preterm delivery (PTD) from fresh embryo transfers (ETs). However, whether the increased risk differs between distinct ovarian stimulation protocols remains unknown. A retrospective cohort study of 38,220 singleton deliveries after fresh single ETs from 2007 to 2013 was conducted. Main outcomes were birth weight and gestational length. Compared with the natural cycle, all ovarian stimulation protocols were associated with a significantly increased risk for PTD, low birth weight (LBW) and small for gestational age (SGA). In subgroup analysis of maternal age under 35 years, luteal support using progesterone, and early cleavage ETs, the significant associations remained for LBW and SGA in gonadotropin-releasing hormone (GnRH) antagonist protocol and for LBW in GnRH agonist protocol. Ovarian stimulation using clomiphene citrate (CC) had the highest increased risks for LBW (Adjusted odds ratio [AOR], 1.58, 95% confidence interval [95% CI], 1.43-1.73) and SGA (AOR, 1.65, 95% CI, 1.50-1.82) compared with natural cycles, and was further associated with PTD and cesarean section. These findings suggest ovarian stimulation was associated with lower birth weight, and CC may have adverse effect on neonatal outcomes in fresh cycles.