Clinical Outcomes of High-Dose Follitropin Delta in POSEIDON (Patient-Oriented Strategies Encompassing Individualized Oocyte Number) Group 4: An Exploratory Case Series on Follicular Efficiency and Embryo Development

Background Patients classified as Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) Group 4 represent a particularly challenging population in assisted reproductive technology (ART), due to advanced age and diminished ovarian reserve. While follitropin delta allows individualized dosing based on body weight and anti-Müllerian hormone (AMH) levels, its standard use in Japan is limited to 12 μg/day. The efficacy of higher off-label doses in this group remains insufficiently studied. Methods This retrospective case series included seven women aged ≥35 years with antral follicle count (AFC) <5 or AMH <1.2 ng/mL, treated at a single clinic between 2022 and 2024. All patients underwent controlled ovarian stimulation (COS) using a gonadotropin-releasing hormone (GnRH) antagonist protocol and received daily follitropin delta at doses of 15 μg. Key outcomes included follicular development, controlled ovarian stimulation (COS) and oocyte pick-up performance, embryological outcomes, and ovarian hyperstimulation syndrome (OHSS) incidence. Results The mean age of the participants was 44.0 years, and the mean AMH was 0.70 ng/mL. The average number of oocytes retrieved was 5.71, with all patients achieving follicle-to-oocyte index (FOI) ≥1.00 (mean 1.52). The mean follicular output rate (FORT) was 1.41. Good-quality blastocysts were obtained in five of seven cases (71.4%). None of the patients had OHSS despite relatively high gonadotropin exposure. No patient discontinued treatment, and the stimulation was well tolerated by all. Conclusion High-dose follitropin delta may represent a feasible and safe option for selected POSEIDON Group 4 patients. However, these findings are preliminary and derived from a small case series without a control group. Further prospective studies are required to confirm efficacy and long-term reproductive outcomes.