Abstract: Objective 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. Methods 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. Results 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). Conclusions 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.

Key words: gonadotropin-releasing hormone antagonist protocol; human menopausal gonadotropin; advanced age; diminished ovarian reserve