Who may benefit from an increased gonadotropin dosing in predicted poor responders undergoing IVF/ICSI? A secondary analysis assessing treatment selection markers of a randomized trial

Objective: To evaluate whether we can identify patient characteristics that serve as treatment selection markers to distinguish which women with expected poor response benefit from increased dosing of follicle-stimulating hormone (FSH) in terms of improving the cumulative live birth rate compared to standard FSH dosing and which women. Study design: We performed a secondary analysis of an RCT performed between March 2019 and October 2021 comparing cumulative live birth after increased dosing (N = 328) who received 225 or 300 IU/day according to their antral follicle count (AFC) and standard dosing (N = 333) who received 150 IU/day of gonadotropin. Results: The MFPI analysis showed the benefit of the increased dosing of FSH on cumulative live birth starts to emerge when women were older than 30 years (women > 30 years: 46.5 % vs. 34.2 %; adjusted relative risk (aRR) 1.32, 95 % confidence interval (95 %CI) 1.05–1.66; women ≤ 30 years: 54.7 % vs. 58.6 %; aRR 0.91, 95 % CI 0.72–1.14; p for interaction 0.019). Only those who had AFC between 1 and 3 benefited from the increased FSH dose (AFC 1–3: 38.5 % vs. 6.5 %; aRR 5.88, 95 % CI 1.50–23.15; AFC 4–9: 50.3 % vs. 46.0 %; aRR 1.08, 95 % CI 0.92–1.27; p for interaction 0.023). Expected poor responders defined by the Bologna criteria and POSEIDON criteria did not significantly benefit from the increased dosing of FSH. Conclusions: Women who are aged >30 years or have AFC 1–3 are likely to benefit from increased dosing of FSH by having a higher cumulative live birth rate.