Association between the total dosage of gonadotropin-releasing hormone antagonist during controlled ovarian stimulation and pregnancy outcomes

Abstract At present, gonadotropin-releasing hormone antagonist (GnRH-ant) protocol is being increasingly used in controlled ovarian stimulation (COS). However, some studies have shown that the GnRH-ant protocol impairs the pregnancy outcomes of fresh embryo transfer owing to the decreased endometrial receptivity caused by the administration of GnRH-ant. The present study aimed to explore whether the total dosage of GnRH-ant was associated with the pregnancy outcomes in infertile women undergoing in vitro fertilization / intracytoplasmic sperm injection (IVF/ICSI) treatment. The study was a retrospective cohort study where data were obtained between 1 November 2019 and 31 October 2024. The study included IVF and ICSI cycles with the GnRH-ant protocol. The primary outcome was the clinical pregnancy rate (CPR) per fresh cycle. The secondary outcomes included embryo implantation rate (IR), early miscarriage rate (EMR). A total of 3,764 infertile women were included and divided into four groups according to the total antagonist dose quartile. No significant differences were observed in baseline demographics among the four groups, except for body mass index (BMI), basal FSH, and basal luteinizing hormone (LH) levels. Gonadotropin (Gn) dosage and COS duration were significantly different among the groups. The CPR, IR, EMR were comparable among the four groups. Logistic regression analysis showed that female BMI, infertility factors, endometrial thickness on the day of the trigger, and the number, grade and quality of transplanted embryos were significantly correlated with the CPR; however, the antagonist dosage did not correlate with the CPR. In conclusion, there was no association between the total GnRH-ant dosage in the GnRH-ant protocol and CPR, IR, EMR after fresh embryo transfer. GnRH-ant should be added promptly during COS with the GnRH-ant protocol. In addition, the total GnRH-ant dosage does not appear to have detrimental effects on the pregnancy outcomes after fresh embryo transfer. Lay summary Gonadotropin-releasing hormone antagonist (GnRH-ant) protocols are widely used for ovarian stimulation in fertility treatments, such as in vitro fertilization. Some research suggested GnRH-ant might affect endometrial receptivity. This could reduce the chances of embryo implantation and pregnancy. Our study included 3,764 women undergoing embryo transfer using the GnRH-ant protocol. Women were grouped by the total GnRH-ant dose they received. We compared implantation, pregnancy, and miscarriage rates across the groups. We found that pregnancy outcomes were similar regardless of the total dose used. Also, higher doses did not reduce the chances of pregnancy after embryo transfer. This suggests doctors can adjust the dose based on each patient’s needs without lowering the chance of success.