P-612 Three different protocols for pituitary suppression: Progestins (dydrogesterone or medroxyprogesterone acetate) versus GnRH antagonist: Balancing Efficacy and Cost in Ovarian Stimulation

Abstract

Abstract Study question Does progesterone-primed ovarian stimulation (PPOS) with dydrogesterone (DYG) or medroxyprogesterone acetate (MPA) and GnRH antagonist protocol differ in efficacy and cost concerning ovarian stimulation (OS)? Summary answer Fixed-dose DYG and flexible-dose MPA provide effective pituitary suppression with similar OS and clinical outcomes and further with lower cost to GnRH antagonists. What is known already While the exact mechanism of progestins remains unclear, their hypothalamic inhibitory effects are likely due to LH suppression. Various studies have validated the efficacy of dydrogesterone, medroxyprogesterone acetate, and micronized progesterone in PPOS protocols. These protocols can follow a fixed or flexible approach based on follicular development. MPA, a synthetic 17α-hydroxyprogesterone derivative, and DYG, a retro-steroidal progestin, exert their effects by binding to progesterone receptors in the hypothalamus without compromising oocyte or embryo quality. This binding reduces GnRH pulse frequency and subsequently suppresses LH secretion. Study design, size, duration This prospective, multicenter cohort study was conducted at two referral in vitro fertilization (IVF) units (Centrum Clinic Assisted Reproduction Center-Ankara and the IVF Center of Bezmialem University Hospital-Istanbul) between March 2023 and March 2024. 307 patients as three treatment groups (DYG group (n = 99), MPA group (n = 101) and GnRH antagonist group (n = 107)) were enrolled into the study. Participants/materials, setting, methods Participants aged 20–43 years, with BMI lt;30 kg/m² and serum AMH gt;1 ng/mL, undergoing IVF were included. OS was initiated on the second or third day of the menstrual cycle. The DYG group received 30 mg/day DYG, orally at the beginning of OS. The MPA group received 10 mg/day MPA and the GnRH antagonist group received 0.25 mg/day cetrorelix once the leading follicle reached 14 mm. All treatments ceased on trigger day. Main results and the role of chance Significant differences were observed in gonadotropin dosage, estradiol on hCG day, and oocytes retrieved. Gonadotropin dosage was highest in the MPA group (2366.98 ± 525.55 IU), followed by the DYD (2168.87 ± 802.74 IU) and the antagonist (2152.62 ± 489.22 IU), with a significant difference between MPA and antagonist groups (p lt; 0.001). Peak estradiol levels on hCG day were significantly higher in the MPA group (2269.58 ± 1097.27 pg/mL) compared to the antagonist group (1859.92 ± 974.59 pg/mL; p = 0.009). The MPA group had significantly more the number of retrieved oocytes (7.33 ± 2.64) compared to the antagonist group (6.84 ± 3.46; p = 0.016) and a greater total number of blastocysts (4.81±1.90), (p = 0.03). No premature ovulations were observed in any group. Pregnancy outcomes, including clinical pregnancy rates (PRs), ongoing pregnancy rates (OGPs), and miscarriage rates, were similar across all groups. The per-patient cost for pituitary suppression during ovarian stimulation was significantly higher for the antagonist group ($959.23 ± 219.18) compared to both the MPA group ($733.29 ± 145.10) and the DYD group ($692.76 ± 204.25; p lt; 0.001). There was no statistically significant difference between the MPA and DYD groups regarding cost (p = 0.105). Limitations, reasons for caution Limitations include non-randomized design and two-center variability in clinical and embryological practices and also live birth rates were not analyzed, limiting comprehensive outcome assessment. Future randomized trials should include LBRs and long-term neonatal outcomes to validate. Wider implications of the findings Fixed-dose DYG and flexible-dose MPA protocols effectively suppress the pituitary and provide similar ovarian stimulation and pregnancy outcomes to GnRH antagonists. Their lower cost positions them as a worthwhile COS alternative. Further randomized studies are essential to confirm findings, explore neonatal outcomes, and assess the long-term safety of these protocols. Trial registration number Yes