Flexible versus fixed progestin-primed ovarian stimulation for preventing premature luteinizing hormone surge in POSEIDON groups 1–2: a non-inferiority randomized controlled trial

Information from the abstract

Progestin-primed ovarian stimulation (PPOS) is an established strategy for preventing premature luteinizing hormone (LH) surge during controlled ovarian stimulation and is considered comparable to Gonadotropin-releasing hormone (GnRH) antagonist protocols. Fixed PPOS regimens are widely used, whereas flexible approaches may reduce progestin exposure and allow treatment individualization. However, comparative evidence between flexible and fixed PPOS remains limited, particularly in suboptimal or normal ovarian reserve women (POSEIDON groups 1–2), and high-quality randomized data are lacking. Ninety-eight infertile women in POSEIDON groups 1–2 undergoing intracytoplasmic sperm injection (ICSI) were randomized (1:1) to flexible or fixed PPOS protocols. Flexible PPOS initiated medroxyprogesterone acetate (MPA) based on follicular size or estradiol level, whereas fixed PPOS started MPA on day 2–3. The primary outcome was the incidence of a premature LH surge on trigger day, analyzed by intention-to-treat using a non-inferiority approach. Secondary outcomes included the number of oocytes retrieved and metaphase II (MII) oocytes, fertilization rate, cleavage rate, blastocyst rate, and the number of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) events. A premature LH surge occurred in 1/49 (2.04%) women in the flexible PPOS group and in 0/49 (0%) in the fixed PPOS group (absolute difference 2.04%, 95% CI − 1.92 to 6.00; p > 0.999), demonstrating non-inferiority of the flexible protocol. Premature ovulation was not observed in either group. In addition, there were no statistically substantial differences between groups in the number of retrieved oocytes and MII oocytes, fertilization rate, cleavage-stage embryos, or blastocysts, including good-quality blastocysts rate. The duration of progestin administration was significantly shorter in the flexible PPOS group, while one patient with moderate to severe OHSS was found in each group (2.04% vs. 2.04%, respectively; p > 0.999). Flexible PPOS demonstrated non-inferior efficacy compared with fixed PPOS in inhibiting premature LH surge in women with suboptimal to normal ovarian reserve having a history of unexpected poor ovarian response (POSEIDON groups 1–2). The flexible approach reduced the duration of progestin exposure without compromising stimulation outcomes or safety, supporting its use as a more individualized and potentially patient-centered strategy. Thai Clinical Trials Registry (No. TCTR20250316002). https://www.thaiclinicaltrials.org/show/TCTR20250316002 . Trial registration date: 06 March 2025 (retrospectively registered).

Why this record is monitored

This record has an Impact Signal of 75/100 based on recency, source, collaboration, and bibliographic signals. It prioritizes monitoring and is not a judgment of research quality.

Related topics: Reproductive Biology and Fertility · Reproductive Health and Technologies · Ovarian function and disorders