This study aimed to compare the effectiveness of the progestin-primed ovarian stimulation (PPOS) protocol versus the antagonist (ATG) protocol for fertility preservation (FP) by oocyte cryopreservation during its early implementation in clinical practice.

We performed a monocentric retrospective case-control (PPOS vs ATG) study and included all FP cycles performed between January 2022 and December 2024, for medical and non-medical reasons. Our main outcome was the mean number of mature oocytes vitrified per cycle. A questionnaire was sent to physicians to assess their concerns about the routine use of the PPOS protocol for FP.

251 cycles were included: 113 in the PPOS group and 138 in the ATG group. Baseline patient and cycle characteristics were globally similar between groups, although some differences in indications were observed. The mean number of mature oocytes vitrified per cycle was significantly lower in the PPOS compared to the ATG group (5.20±4.15 vs 6.81±6.64, p=0.03), as were the mean number of retrieved oocytes per cycle (7.88±6.54 vs 9.89±8.91, p=0.04) and the mean number of follicles >10 mm on trigger day (10.84±6.61 vs 12.99±8.10, p=0.02). Linear regression analyses showed a significant difference in favor of ATG (coefficient 1.61 (0.19-3.02), p=0.03), difference not shown with the multivariate regression (coefficient 1.06 (0.27-2.39), p=0.12). All physicians addressed concerns regarding the use of the PPOS protocol during its implementation, mainly related to the risk of premature ovulation (n=5).

The number of mature oocytes vitrified with PPOS and the ATG protocol in FP cycles yielded similar results on multivariate analysis. Physicians should avoid unnecessarily shortening stimulation and should not overestimate the risk of premature ovulation during early implementation of PPOS. Training needs to continue regarding the different type of progestins used and their duration before the stimulation.