Response-equivalent dosing of follitropin alfa and follitropin delta in Japanese women: a cross-fitted retrospective cohort study

Background To develop a Japanese population-specific empirical conversion between follitropin alfa IU and follitropin delta µg based on comparable ovarian response and to evaluate its response and clinical consistency. Methods This retrospective single-center cohort included 231 first cycles with follitropin alfa and 154 with follitropin delta. Overlap weighting balanced age, body weight, antral follicle count, anti-Müllerian hormone, basal FSH, and basal LH. Inverse response calibration incorporated oocyte yield, follicle-to-oocyte index (FOI), and follicular output rate (FORT). Five-fold cross-fitting assessed coefficient stability and held-out response equivalence. Follicular, endocrine, embryological, and reproductive outcomes were additionally compared at cross-fitted response-equivalent doses. Results The conversion was follitropin delta (µg/day) = 4.581 + 0.02244 ×follitropin alfa (IU/day) (R 2 = 0.704), corresponding to 7.95, 9.63, and 11.31 µg for 150, 225, and 300 IU. Fold-specific slopes ranged from 0.02144 to 0.02327 µg/IU. In held-out observations, FOI (difference −0.033; 90% CI, −0.097 to 0.031) and FORT (0.001; −0.097 to 0.100) met ±0.10 equivalence margins, whereas oocyte yield (−1.40; −2.65 to −0.15) did not meet the ±2-oocyte margin. Follicular, embryological, and cumulative reproductive outcomes were broadly consistent between preparations across response-equivalent dose levels. Conclusion This Japanese population-specific conversion was stable across cross-fitting and supported response equivalence for FOI and FORT. Clinical outcome analyses further supported the consistency of the proposed response-equivalent dose relationship. Clinical trial registration https://jrct.mhlw.go.jp/en-latest-detail/jRCT1031260453 , This observational study was registered in the Japan Registry of Clinical Trials jRCT1031260453.