Clomiphene citrate throughout the duration of ovarian stimulation in patients with diminished ovarian reserve: an approach to decrease costs, reduce injection burden, and prevent premature ovulation.

Abstract

Purpose: Clomiphene citrate (CC) is often utilized as an adjunct in in vitro fertilization (IVF) protocols during the first 5 days of stimulation for endogenous FSH release. However, due to its antiestrogenic mechanism of action, CC may also effectively prevent the LH surge, and hence premature ovulation, if continued until the day of trigger. The objective of this study was to evaluate a "long CC" protocol, in which CC is continued throughout the entire cycle in-lieu of GnRH antagonist, and to compare IVF outcomes with a standard 5-day CC + GnRH antagonist protocol in patients with diminished ovarian reserve (DOR) undergoing IVF with high-dose gonadotropins.

Methods: This is a retrospective cohort study of all CC-based IVF cycles at a single institution between 9/2020 and 9/2022. Mild stimulation protocols were excluded. The long CC group received CC throughout the entire cycle without GnRH antagonist. The CC + GnRH antagonist group received CC for the first 5 days of stimulation followed by GnRH antagonist when the lead follicle reached 14 mm. The primary outcome was mature oocyte yield.

Results: There were 361 cycles (77%) in the long CC group and 108 (23%) in the 5-day CC + GnRH antagonist group. Age and AMH levels were similar between the two groups. There was no significant difference in mature oocyte yield between the long CC and 5-day CC + GnRH antagonist groups (median 5 (IQR 5) vs. 4.5 (IQR 5), respectively, (P = 0.922)). MII oocytes/AFC did not differ (0.69 vs. 0.56, respectively, P = 0.16). Premature ovulation occurred in 0.3% of cycles in the long CC group vs. 3.0% of cycles in the 5-day CC + GnRH antagonist group (P = 0.019).

Conclusions: In DOR patients undergoing IVF, a long CC protocol is an effective and patient-friendly approach associated with non-inferior oocyte yield.