The greater incidence of small‐for‐gestational‐age newborns after gonadotropin‐stimulated in vitro fertilization with a supraphysiological estradiol level on ovulation trigger day

INTRODUCTION: Reproductive scientists have postulated various risk factors for lower birthweight following conventional gonadotropin‐stimulated in vitro fertilization compared with spontaneously conceived children: parental factors (age, health, duration of subfertility and smoking habits); ovarian stimulation; laboratory procedures; the number of oocytes retrieved and the number of embryos transferred. Our aim was to investigate the impact of gonadotropin stimulation and serum estradiol level on the risk of a newborn being small‐for‐gestational‐age. MATERIAL AND METHODS: We conducted a cohort study (2010‐2016) of singletons (n = 155) born either after conventional gonadotropin‐stimulated in vitro fertilization (using ≥150 IU/d human gonadotropin for stimulation) or after natural cycle in vitro fertilization without any stimulation. We analyzed perinatal outcomes using birthweight percentiles, adjusted for gestational age and sex. RESULTS: The proportion of small‐for‐gestational‐age was 11.8% following conventional gonadotropin‐stimulated in vitro fertilization and 2.9% after natural cycle in vitro fertilization (P = 0.058). The odds of small‐for‐gestational‐age were significantly higher with supraphysiological estradiol levels in maternal serum on ovulation trigger day (unadjusted odds ratio 4.58; 95% confidence interval 1.35‐15.55; P = 0.015). It remained significant after adjusting for maternal height, age and body mass index (adjusted odds ratio 3.83; 95% confidence interval 1.06‐13.82; P = 0.041). CONCLUSIONS: We found an associated risk of children being born small‐for‐gestational‐age after conventional gonadotropin‐stimulated in vitro fertilization compared with natural cycle in vitro fertilization. This higher risk is significantly associated with supraphysiological estradiol levels. We propose a reduction in the dosage of gonadotropin to minimize the risk of small‐for‐gestational‐age and future health consequences.