Abstract / Summary
Abstract Background Follitropin delta, a recombinant Follicle-stimulating hormone (FSH) with higher biopotency due to its human cell line origin, is approved with an individualised dosing algorithm for GnRH antagonist protocols with fresh transfer. However, this algorithm faces practical limitations in freeze-all cycles. While novel simplified follitropin delta dosing regimens have shown promise in GnRH antagonist protocols, evidence for such approaches in progestin protocol, an increasingly adopted alternative for freeze-all IVF cycles, remains absent. Methods A multicenter retrospective cohort study (May 2023–September 2024) at three tertiary hospitals including women undergoing their first IVF/ICSI cycle with progestin protocol. Women received follitropin delta at one of three fixed starting doses (9, 12, or 18 µg/day) or follitropin alfa (150, 225, or 300 IU/day) based on anti-Müllerian hormone (AMH) stratification. Propensity score matching was performed on age, Body Mass Index (BMI), AMH, and antral follicle count. Primary outcome was live birth after first frozen embryo transfer (FET) cycle. Results After matching, 342 women per group were analysed for stimulation and laboratory outcomes; 315 (alfa) and 314 (delta) completed first FET analysis. The live birth rate after first FET was comparable between the follitropin delta and follitropin alfa groups (40.1% vs. 41.6%; relative risk [RR] 0.97, 95% confidence interval [CI] 0.8–1.2; p = 0.8). Compared with the follitropin alfa group, the follitropin delta group had a shorter stimulation duration (median 8 vs. 9 days, p < 0.001), while maintaining a similar number of ≥ 14 mm follicles and number of oocytes retrieved. Other embryological, pregnancy, and neonatal outcomes were also comparable between groups. No case of ovarian hyperstimulation syndrome occurred. Conclusion In women undergoing IVF/ICSI with freeze-all indications using the progestin protocol, the novel pragmatic fixed-dose stratified follitropin delta regimen achieved comparable live birth rates following the first FET when compared with an AMH-stratified follitropin alfa regimen, with a shorter stimulation duration. While these findings suggest that this pragmatic regimen may offer clinical efficiency, well-designed prospective randomised controlled trials are required before it can be routinely recommended in clinical practice.