Antifibrotic drug finerenone restores fertility in premature ovarian insufficiency.

Currently, no effective treatment exists for infertility associated with premature ovarian insufficiency (POI) because affected patients lack hormone-responsive antral follicles. By screening a Food and Drug Administration (FDA)-approved drug library, we identified finerenone, a kidney disease medication, as a promising drug for restoring fertility in POI. Finerenone stimulated follicle development in aged mice and restored antral follicle development in patients with POI following oral administration, resulting in mature oocytes and embryos. Mechanistically, finerenone reduced fibrotic deposition in the ovarian stroma, alleviating collagen-mediated suppression of follicular development. Building on this insight, we identified additional FDA-approved oral antifibrotic drugs as potential treatments for POI-related infertility. Our findings highlight the ovarian stroma-rather than the follicles themselves-as the key therapeutic target and offer potential therapeutic leads for POI-related infertility.