Fertility preservation in women with endometriosis: A retrospective non-Inferiority study comparing Dienogest in the PPOS protocol to antagonist and agonist protocols

Abstract

Background: Endometriosis is a common pathology that can lead to a decrease in fertility and is therefore a medical indication for preserving fertility. Traditionally, gonadotropin-releasing hormone (GnRH) antagonist and agonist protocols are used to stimulate the ovaries. However, the recent introduction of the progestin-primed ovarian stimulation (PPOS) protocol, using progestins to prevent LH surges, offers a new alternative. Dienogest, a progestin commonly used to treat endometriosis, could be incorporated into the PPOS protocol for patients with endometriosis, allowing them to maintain their background therapy during ovarian stimulation. The aim of this study was to assess the non-inferiority of using Dienogest in the PPOS protocol compared to antagonist and agonist protocols in terms of the number of mature oocytes retrieved from patients with endometriosis undergoing fertility preservation (FP).

Methods: This retrospective, multicenter, non-inferiority study was conducted in patients with endometriosis, comparing the PPOS protocol with Dienogest, the antagonist protocol, and the agonist protocol. The primary endpoint was the number of mature oocytes retrieved. The secondary endpoint included ovarian response parameters, treatment complications, and tolerance assessed by validated questionnaires.

Results: The study included 201 cycles performed in 130 patients. Non-inferiority of the PPOS-Dienogest protocol was demonstrated in pairwise comparisons against antagonist protocol (p = 0.0062) and agonist protocol (p = 0.0360) in the number of mature oocytes retrieved. Using Dienogest in the PPOS protocol was not associated with a smaller number of mature oocytes retrieved than with the GnRH antagonist or agonist conventional protocols. Additionally, no significant differences were found in ovarian response parameters, treatment tolerance, or complications between protocols.

Conclusion: The PPOS protocol with Dienogest appears to be a promising alternative for FP compared to traditional protocols for patients with endometriosis, without adversely affecting the number of mature oocytes retrieved. Larger prospective studies are required to confirm these results.

Keywords: Controlled ovarian stimulation; Dienogest; Diénogest; Endometriosis; Endométriose; Fertility preservation; PPOS; Préservation de fertilité; Stimulation ovarienne.