L26/O-211 Dienogest-based progestin-primed ovarian stimulation versus GnRH antagonist in IVF: a preliminary comparative cohort study

Abstract Study question Does Dienogest-based progestin-primed ovarian stimulation (PPOS) provide comparable ovarian response and embryological outcomes to GnRH antagonist protocols in freeze-all IVF cycles? Summary answer Dienogest-based PPOS provides ovarian and embryological outcomes comparable to GnRH antagonist protocols, with a significantly higher fertilization rate. What is known already Progestin-primed ovarian stimulation (PPOS) is an established alternative to GnRH analogues for pituitary suppression in freeze-all IVF cycles, with comparable ovarian response, embryo development, and reproductive outcomes. Most available evidence concerns medroxyprogesterone acetate and dydrogesterone. Meta-analyses on these progestins consistently support the biological neutrality of progestin exposure on oocyte competence. Dienogest is widely used for long-term management of endometriosis and has favorable pharmacokinetic and pharmacodynamic properties, making it a biologically attractive candidate for PPOS. However, its use in conventional IVF is currently supported by limited, small, and heterogeneous studies. Study design, size, duration The present study is a monocentric, observational cohort study with combined retrospective and prospective enrollment, reported according to STROBE guidelines. The dienogest-based PPOS group was recruited entirely prospectively, whereas the GnRH antagonist cohort was assembled through both prospective and retrospective inclusion to achieve the predefined sample size. Overall, 409 consecutive IVF cycles were analyzed between January 2025 and October 2025. Participants/materials, setting, methods Women aged 18-45 years undergoing IVF with freeze-all strategy at a tertiary ART center were included. Controlled ovarian stimulation (COS) was performed using either PPOS-Dienogest 2 mg/day or a flexible GnRH antagonist. The primary outcome was the number of metaphase II (MII) oocytes. Secondary outcomes included estradiol levels, COS duration, fertilization, blastulation, and cycle cancellation. Pregnancy and live birth outcomes will be available at final analysis. Multivariable regression adjusted for age, BMI, endometriosis, and AMH. Main results and the role of chance Baseline differences included significant younger age, higher AMH, greater endometriosis prevalence and higher BMI in the Dienogest group. The mean MII oocytes retrieved were similar: 5.6 for the Dienogest group and 5.0 for the antagonist group (p = 0.18), with this difference remaining non-significant after adjustment (b = +0.05, 95% BCa CI − 0.30 to + 0.36). Total oocytes retrieved, blastulation rate, frozen blastocysts availability and cycle cancellation rate did not differ in both unadjusted and adjusted analyses. Fertilization rate was significantly higher with Dienogest (82.9% vs 77.3%, p = 0.026), remaining significant even after adjustment (b = +2.0%, 95% BCa CI 0.4–3.5). In the multivariable regression analysis, estradiol levels at trigger were lower with Dienogest (b = −112 pg/mL), and stimulation duration was slightly longer (b = +0.23 days). Independent negative predictors of MII oocytes and blastocyst availability were age >40, obesity, and endometriosis, while AMH was the strongest positive predictor. Notably, in all models, stimulation protocol was not independently associated with ovarian or embryological outcomes. Limitations, reasons for caution The observational design and baseline imbalances may limit causal inference. As a tertiary referral center for endometriosis, population characteristics may not reflect unselected IVF cohorts. This preliminary analysis includes laboratory outcomes only; pregnancy and live birth data are pending. Wider implications of the findings By showing no detrimental effect on ovarian and embryological outcomes, these data support further investigation of Dienogest-based PPOS as a strategy potentially enabling a therapeutic continuum between chronic disease management and IVF, particularly in women with endometriosis, a hypothesis requiring confirmation in dedicated prospective studies. Trial registration number No