{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:22:51Z","timestamp":1792653771618,"version":"4.5.0"},"reference-count":154,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Imam Mohammad Ibn Saud Islamic University","award":["IMSIU-DDRSP2601"],"award-info":[{"award-number":["IMSIU-DDRSP2601"]}]},{"award":["IMSIU-DDRSP2601"],"award-info":[{"award-number":["IMSIU-DDRSP2601"]}],"id":[{"id":"https:\/\/ror.org\/05gxjyb39","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Polycystic ovarian syndrome (PCOS) is a complex endocrine and metabolic disorder that affects reproductive health, metabolic function, and long-term cardiovascular health in women of reproductive age. The syndrome is characterized by hyperandrogenism, chronic anovulation, insulin resistance, oxidative stress, and ovarian microenvironment remodeling. While current treatments focus on symptom relief through hormone regulation, insulin sensitizers, or ovulation induction, there is a need to target the underlying molecular and cellular processes that drive disease progression and infertility. Breakthroughs in reproductive and metabolic medicine have led to the development of next-generation therapeutics for PCOS that aim to restore ovarian function at the molecular level. Nanoparticle- and nanofiber-based drug delivery systems offer targeted delivery to the ovaries, improved bioavailability, and controlled release of insulin sensitizers, antioxidants, and anti-androgens. Metabolic reprogramming strategies that target insulin resistance, mitochondrial dysfunction, and autophagy have emerged as potential disease-modifying interventions. In addition, AI-enabled precision medicine approaches are reshaping PCOS management through phenotype-based classification, predictive modeling, and personalized fertility optimization. In this review, we highlight recent advancements in understanding the molecular pathophysiology of PCOS and introduce novel therapeutics that harness intelligent drug delivery, ovarian microenvironment restoration, and AI-based interventions. We discuss the potential of these innovative strategies to update PCOS management options for long-term ovarian restoration and fertility.<\/jats:p>","DOI":"10.3390\/biom16050626","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T09:09:12Z","timestamp":1776935352000},"page":"626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Modern Polycystic Ovary Syndrome (PCOS) Management: Intelligent Drug Delivery and Metabolic Reprogramming for Ovarian Restoration and Fertility Optimization"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2170-1303","authenticated-orcid":false,"given":"Abdel Halim","family":"Harrath","sequence":"first","affiliation":[{"name":"Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maroua","family":"Jalouli","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Al-Zharani","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6649-3694","authenticated-orcid":false,"given":"Md Ataur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41574-024-01057-w","article-title":"Polycystic ovary syndrome as a metabolic disease","volume":"21","author":"Helvaci","year":"2025","journal-title":"Nat. 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