Three different protocols for pituitary suppression: progestins (dydrogesterone or medroxyprogesterone acetate) versus GnRH antagonist-balancing efficacy and cost in ovarian stimulation

PURPOSE: To compare the clinical effectiveness and overall treatment cost of three ovarian stimulation protocols-dydrogesterone (DYD), medroxyprogesterone acetate (MPA), and GnRH antagonist-in women undergoing in vitro fertilization (IVF). METHODS: This prospective, multicenter cohort study was conducted at two IVF units from March 2023 to March 2024. A total of 307 women undergoing IVF were divided into three groups based on their pituitary suppression protocol: DYD (n = 99), MPA (n = 101), and GnRH antagonist (n = 107). Ovarian stimulation parameters, pregnancy outcomes, and detailed cost analyses were then compared across these groups. RESULTS: The number of mature oocytes (MII) retrieved and follicular output rate (FOI) were comparable among the three groups (MII, p = 0.67; FOI, p = 0.74). Gonadotropin consumption and estradiol levels on trigger day were significantly higher in the MPA group (p < 0.001 and p = 0.009, respectively). Clinical pregnancy rates (DYD 37.4%, MPA 32.7%, GnRH antagonist 34.6%; p = 0.78) and ongoing pregnancy rates (DYD 32.3%, MPA 28.7%, GnRH antagonist 29.9%; p = 0.85) did not differ significantly among groups. While the LH suppression cost per cycle was highest in the GnRH antagonist group (257.7 USD), the total cycle cost for this group was the lowest, as it typically involves fresh embryo transfer compared to frozen embryo transfer (FET) in PPOS (progestin-primed ovarian stimulation) protocols. CONCLUSION: PPOS protocols (DYD or MPA) offer clinical outcomes comparable to the GnRH antagonist protocol. While PPOS regimens may provide cost advantages in freeze-all settings due to lower LH suppression, the overall economic benefit hinges on the embryo transfer strategy. Therefore, optimal protocol selection should be individualized, considering both clinical characteristics and cost.