The impact of different endometrial preparation protocols on obstetric and neonatal complications in frozen-thawed embryo transfer: a retrospective cohort study of 3,458 singleton deliveries

Background Frozen-thawed embryo transfer (FET) is thought to be associated with obstetric and neonatal complications after in vitro fertilization/intracytoplasmic single sperm injection (IVF/ICSI) treatment. The study aimed to determine whether the endometrial preparation protocol is an influencing factor for these complications. Methods We conducted a retrospective cohort study of 3,458 women who had singleton deliveries after IVF/ICSI-FET treatment at the Centre for Reproductive Medicine of Shanghai First Maternity and Infant Hospital between July 2016 and April 2021. The women were divided into three groups according to the endometrial preparation protocols: 2,029 women with programmed cycles, 959 with natural cycles, and 470 with minimal ovarian stimulation cycles. The primary outcomes were the incidence rates of obstetric and neonatal complications, namely, hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), placenta previa, preterm rupture of membranes (PROM), preterm delivery, postpartum haemorrhage, large for gestational age (LGA), small for gestational age (SGA), and macrosomia. Results After adjustments for confounding variables by multivariate logistic regression analysis, the results showed that programmed cycles had an increased risk of HDP (aOR = 1.743; 95% CI, 1.110-2.735; P = 0.016) and LGA (aOR = 1.269; 95% CI, 1.011-1.592; P = 0.040) compared with natural cycles. Moreover, programmed cycles also increased the risk of LGA (aOR = 1.459; 95% CI, 1.083-1.965; P = 0.013) but reduced the risk of SGA (aOR = 0.529; 95% CI, 0.348-0.805; P = 0.003) compared with minimal ovarian stimulation cycles. There were no significant differences between natural cycles and minimal ovarian stimulation cycles. Conclusions During IVF/ICSI-FET treatment, the risk of HDP and LGA was increased in women with programmed cycles. Therefore, for patients with thin endometrium, irregular menstruation or no spontaneous ovulation, minimal ovarian stimulation cycles may be a relatively safer option than programmed cycles.