Timing of HMG supplementation and clinical outcomes of advanced-age patients with diminished ovarian reserve receiving gonadotropin-releasing hormone antagonist protocol

Abstract

To assess the effect and timing of human menopausal gonadotropin (HMG) supplementation in advancedage patients with diminished ovarian reserve (DOR) receiving gonadotropin-releasing hormone antagonist protocol. A total of 682 patients with DOR aged over 35 years undergoing IVF-ET treatment were included in this study. All the patients underwent a GnRH antagonist protocol, and controlled ovarian stimulation was initiated on day 2-3 of the menstrual cycle with follicle stimulation hormone (FSH). According to the timing of HMG supplementation, the patients were divided into no supplementation group (n=371) without HMG supplementation; early supplementation group (n=139), in which daily HMG supplementation started on the first day till the trigger day; and late supplementation group (n=172), in which HMG supplementation started when the leading follicle reached 10-14 mm in diameter and lasted until the trigger day. The pregnancy outcomes of the patients were compared among the 3 groups. The 3 groups showed no significant difference in hCG trigger day E2 and P levels, endometrial thickness, or the number of follicles with comparable fertilization rate and cleavage rate (P>0.05). Gn dose used was the lowest in no supplementation group, and the average number of oocytes retrieved was significantly smaller in early supplementation group than in late supplementation group (P < 0.05). The mean number of mature oocytes and embryos available were significantly higher in late supplementation group than in early supplementation group (P < 0.05). The clinical pregnancy rate of fresh embryo transfer cycle was significantly higher in late supplementation group than in no supplementation group (27.7% vs 45.1%, P < 0.05), but the implantation rate, early miscarriage rate, heterotopic pregnancy rate and live birth rate were comparable among the 3 groups (P>0.05). No significant differences were found among the 3 groups in the implantation rate, clinical pregnancy rate, early miscarriage rate, heterotopic pregnancy rate or live birth rate of the first frozen-thawed embryo transfer cycle with a freeze-all strategy (P>0.05). HMG supplementation in the middle and late follicular phase can improve the outcomes of controlled ovarian hyperstimulation and increase the clinical pregnancy rate of fresh embryo transfer cycle in advanced-age patients with DOR undergoing GnRH antagonist protocol.