{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:07:37Z","timestamp":1792789657984,"version":"4.5.0"},"reference-count":136,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T00:00:00Z","timestamp":1710892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fonds National de la Recherche Scientifique de Belgique","award":["FNRS-PDR T.0064.22"],"award-info":[{"award-number":["FNRS-PDR T.0064.22"]}]},{"name":"Fonds National de la Recherche Scientifique de Belgique","award":["CDR J.0063.20"],"award-info":[{"award-number":["CDR J.0063.20"]}]},{"name":"Fonds National de la Recherche Scientifique de Belgique","award":["5\/4\/150\/5"],"award-info":[{"award-number":["5\/4\/150\/5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Ovarian tissue cryopreservation (OTC) and subsequent transplantation (OTT) is a fertility preservation technique widely offered to prepubertal girls and young fertile women who need to undergo oncological treatment but are at a high risk of infertility. However, OTT is not considered safe in patients with certain diseases like leukemia, Burkitt\u2019s lymphoma, and ovarian cancer because of the associated risk of malignant cell reintroduction. In vitro follicle development has therefore emerged as a promising means of obtaining mature metaphase II (MII) oocytes from the primordial follicle (PMF) pool contained within cryopreserved ovarian tissue, without the need for transplantation. Despite its significant potential, this novel approach remains highly challenging, as it requires replication of the intricate process of intraovarian folliculogenesis. Recent advances in multi-step in vitro culture (IVC) systems, tailored to the specific needs of each follicle stage, have demonstrated the feasibility of generating mature oocytes (MII) from early-stage human follicles. While significant progress has been made, there is still room for improvement in terms of efficiency and productivity, and a long way to go before this IVC approach can be implemented in a clinical setting. This comprehensive review outlines the most significant improvements in recent years, current limitations, and future optimization strategies.<\/jats:p>","DOI":"10.3390\/jcm13061791","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T10:44:33Z","timestamp":1710931473000},"page":"1791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Comprehensive Review of In Vitro Human Follicle Development for Fertility Restoration: Recent Achievements, Current Challenges, and Future Optimization Strategies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3792-0276","authenticated-orcid":false,"given":"Francisco","family":"Vitale","sequence":"first","affiliation":[{"name":"Gynecology Research Unit, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain, Avenue Mounier 52, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6331-3026","authenticated-orcid":false,"given":"Marie-Madeleine","family":"Dolmans","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain, Avenue Mounier 52, 1200 Brussels, Belgium"},{"name":"Gynecology Department, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/humupd\/7.6.535","article-title":"The Effects of Radiotherapy and Chemotherapy on Female Reproduction","volume":"7","author":"Meirow","year":"2001","journal-title":"Hum. 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