Exogenous FSH overrides age-related elevated FSH and can enforce multiple follicle growth in women undergoing IUI, a randomized controlled trial

Purpose: To determine whether recombinant follicle‑stimulating hormone (r‑FSH) increases multifollicular development versus natural‑cycle management in women with elevated basal FSH (b‑FSH) undergoing intrauterine insemination (IUI), and to evaluate predictors (cycle‑start FSH, anti‑Müllerian hormone [AMH], antral follicle count [AFC], and FSH‑receptor polymorphism). Methods: Open‑label randomized controlled trial at a university center including 48 women allocated to a natural group (n=23; three natural then three stimulated cycles) or a stimulated group (n=25; six stimulated cycles). Stimulated cycles began with 150 IU/day r‑FSH, with 75‑IU increments in subsequent cycles if multifollicular growth did not occur. The primary outcome was multifollicular growth (≥2 follicles ≥14 mm on hCG day). Results: Baseline characteristics were comparable. The stimulated group had a 2.7‑fold higher likelihood of multifollicular growth than the natural group (95% CI 1.16–6.11; P=0.02). Lower cycle‑start FSH predicted multifollicular growth (odds ratio per IU/L 0.81; 95% CI 0.72–0.91; P=0.0003). Among women with detectable AMH, mean AMH was 0.68 µg/L (natural) and 0.44 µg/L (stimulated). AMH was undetectable in five women. Twelve pregnancies occurred with AMH ≤0.5 µg/L; one pregnancy occurred despite undetectable AMH. Conclusions: In women with elevated b‑FSH undergoing IUI, r‑FSH stimulation increases the probability of multifollicular growth. Controlled ovarian stimulation should be to maximize multifollicular development and potentially ongoing pregnancy. Extremely low or undetectable AMH does not preclude conception and should not alone justify denial of treatment. The trial was retrospectively registered in the Dutch trial register (ISRCTN14825568) on 13-12-2005. Capsule Summary Randomized study in women with elevated basal FSH undergoing IUI: stimulation with r‑FSH increased multifollicular growth (OR 2.7; 95% CI 1.16–6.11). Lower cycle‑start FSH predicted response. Pregnancies occurred even with AMH ≤0.5 µg/L or undetectable, arguing against withholding treatment solely for very low AMH.