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By screening a Food and Drug Administration (FDA)\u2013approved 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\u2014rather than the follicles themselves\u2014as the key therapeutic target and offer potential therapeutic leads for POI-related infertility.<\/jats:p>","DOI":"10.1126\/science.adz4075","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T19:00:52Z","timestamp":1770318052000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":22,"title":["Antifibrotic drug finerenone restores fertility in premature ovarian insufficiency"],"prefix":"10.1126","volume":"391","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0751-2352","authenticated-orcid":true,"given":"Zexiong","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China."},{"name":"Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted 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