Progestin-primed Ovarian Stimulation With Clomiphene Citrate Compared With the Standard Progestin-primed Ovarian Stimulation in Various Aged Women With Diminished Ovarian Reserve: a Retrospective Study

Background: Clomiphene citrate (CC) supplementation in the progestin-primed ovarian stimulation (PPOS) protocol effectively alleviated profound pituitary suppression from progestin administration and reduced the gonadotropin (Gn) dose in the population of women with normal-ovarian-reserve or polycystic ovarian syndrome. Limited data are available about the role of CC in PPOS for women with diminished ovarian reserve (DOR). This study aimed to compare the efficiency of the PPOS protocol with CC supplementation and the standard PPOS protocol for various aged women with DOR.Methods: A total of 364 patients with DOR were recruited for this retrospective cohort study. They were divided into subgroups based on female age, ≤35 years and ＞35 years. The clinical characteristics and outcome were compared between the groups in subgroups.Results: In all patients with DOR, the PPOS protocol with CC supplementation was associated with a lower percentage of women with profound pituitary suppression (0.0% vs 18.6%, P ＜0.001 and 1.3% vs 11.0%, P ＝0.002) and a higher mean luteinizing hormone (LH) level during controlled ovarian stimulation (COS) than the standard PPOS protocol (P ＜0.05＝. In young women with DOR, more number of high-quality cleavage-stage embryos (1.96 vs. 1.38, P ＝0.018) was achieved in the PPOS protocol with CC supplementation. In elderly women with DOR, PPOS protocol with CC supplementation led to an increase in the incidence of LH levels above 10 IU/L on the trigger day (12.7% vs. 4.9%, P ＝0.028) and decrease in the rate of oocyte maturation (84.7% vs. 89.9%, P ＝0.034) compared to the standard PPOS protocol. No significant differences were observed in the Gn duration, total dosage of Gn, and pregnancy outcomes between the groups. Conclusions: CC is an effective adjuvant to alleviate pituitary suppression in the PPOS protocol. For young women with DOR, CC supplementation has a positive impact on the number of high-quality embryos in PPOS protocol. However, elderly patients with DOR would be at risk of developing premature LH surge and poor oocyte maturation rate after the PPOS protocol with CC supplementation was applied.