Follitropin Beta as a Rescue Protocol for Poor Responders to Follitropin Delta: A Retrospective Within-Patient Paired Study

Background and objective Follitropin delta (Rekovelle®) is administered using an individualized dosing algorithm based on anti-Müllerian hormone (AMH) and body weight, with a maximum dose of 12 μg/day in the first cycle. In patients who respond poorly to follitropin delta, alternative gonadotropins permitting higher dose administration, such as follitropin beta (Follistim®), may be considered. However, no within-patient study has examined whether switching to follitropin beta can rescue poor responders to follitropin delta. This study aims to evaluate whether switching to follitropin beta as a rescue protocol improves the number of oocytes retrieved and the quality of embryos in patients who responded poorly to follitropin delta, using a within-patient paired design. Methods This retrospective, single-center, within-patient paired study included patients who underwent follitropin delta antagonist-protocol cycles with letrozole co-administration and were subsequently switched to follitropin beta with letrozole co-administration due to poor ovarian response between January 2024 and April 2026. The last follitropin delta cycle, representing the poor-response cycle that triggered the treatment switch, and the first follitropin beta cycle per patient were analyzed as sequential matched pairs (n = 35). The primary outcome was the number of retrieved oocytes. Secondary outcomes included the number of metaphase II (MII) oocytes, transferable blastocysts, and high-quality blastocysts. The Wilcoxon signed-rank test was used. All follitropin delta cycles were administered at the maximum approved dose of 12 μg/day (approximately 180 IU), whereas all follitropin beta cycles were initiated at 300 IU/day. Results Median AMH was 0.64 ng/mL (interquartile range, 0.26-1.29), and median age was 40 years. In the subsequent follitropin beta cycles, the number of retrieved oocytes showed a trend toward an increase compared with the preceding follitropin delta cycles (median 6.0 (IQR 3.0-9.0) vs. 5.0 (IQR 3.0-7.0); p = 0.057; n = 35), with improvement in 19 of 35 patients. The number of MII oocytes was also numerically higher in follitropin beta cycles but did not reach statistical significance (median 5.0 (IQR 2.0-7.0) vs. 4.0 (IQR 2.0-5.0); p = 0.195). No significant differences were observed in transferable blastocysts (median 2.0 (IQR 0.5-4.0) vs. 2.0 (IQR 1.0-2.0); p = 0.123) or high-quality blastocysts (median 0.0 (IQR 0.0-1.0) vs. 0.0 (IQR 0.0-1.0); p = 0.060) between the two sequential cycles. Conclusion In patients who responded poorly to follitropin delta, switching to follitropin beta as a rescue protocol was associated with a trend toward increased oocyte retrieval, and no differences were observed in embryologic outcomes. These exploratory findings do not constitute evidence of a treatment benefit but may serve as a basis for hypothesis generation. Larger prospective studies are warranted.