Comparing algorithm-tailored follitropin delta versus follitropin alpha dosing in expected poor responders: a cohort analysis

BACKGROUND: Expected poor ovarian responders represent a challenging population in assisted reproduction, in whom controlled ovarian stimulation requires a careful balance between achieving an adequate oocyte yield and limiting cycle cancellation and treatment burden. Algorithm-based follitropin delta dosing has been proposed as an alternative to conventional high-dose follitropin alpha regimens, but comparative real-world data in this population remain limited. METHODS: This retrospective single-center matched cohort study included 423 women fulfilling the Bologna criteria for poor ovarian response undergoing IVF/ICSI. Ovarian stimulation was performed with either algorithm-based follitropin delta (12 mcg/day; N.=141) or follitropin alpha at a minimum daily starting dose of 225 IU (N.=282). Groups were matched for age, ovarian reserve markers, body weight, year of treatment, and recombinant LH supplementation. The primary outcome was the number of oocytes retrieved. Secondary outcomes included ovarian stimulation characteristics, progesterone (P) levels at hCG trigger, incidence of premature progesterone elevation (PPE), feasibility of fresh embryo transfer, and cumulative pregnancy outcomes. RESULTS: Follitropin delta was associated with a lower number of oocytes retrieved (IRR 0.847, 95% CI 0.733-0.979; P=0.025) and mature oocytes (IRR 0.823, 95% CI 0.703-0.963; P=0.016) compared with follitropin alpha. P levels at hCG trigger were significantly lower with follitropin delta (median 0.4 ng/mL, IQR 0.3-0.6) than with follitropin alpha (0.6 ng/mL, IQR 0.4-0.9; P<0.001), resulting in a reduced incidence of PPE (5.4% vs. 16.7%; P=0.006) and a higher likelihood of fresh embryo transfer (64.6% vs. 52.1%; P=0.023). Fertilization rates, embryo development, and cumulative pregnancy outcomes did not differ significantly between groups. CONCLUSIONS: In expected poor responders, algorithm-based follitropin delta resulted in a lower oocyte yield compared with conventional follitropin alpha dosing, while reducing PPE and increasing the feasibility of fresh embryo transfer, without a clear impact on cumulative pregnancy outcomes.