{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:52:54Z","timestamp":1793407974305,"version":"4.5.0"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005725","name":"National Plan for Science, Technology and Innovation","doi-asserted-by":"publisher","award":["13-MED1375-02"],"award-info":[{"award-number":["13-MED1375-02"]}],"id":[{"id":"10.13039\/501100005725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Evidence supports the benefits of hydroxyurea (HU) in adults with sickle cell disease (SCD), but reservations remain due to long-term concerns of fertility. Retrospective analysis of clinical records of SCD patients (haemoglobin SS genotype) have identified gender-related differences in disease progression. This could inform risk stratification during SCD at diagnosis with the possibility to guide therapeutic decisions.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This systemic review and meta-analysis evaluated fertility parameters in both children (aged \u2265 6 years) and adults with SCD receiving HU therapy. Studies were sourced from PubMed and EMBASE from inception to July 2023. A total of 160 potentially relevant articles were identified.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Four studies were included that evaluated the effects of HU on sperm parameters in males. A further 4 studies assessed anti-mullerian hormone (AMH) levels and ovarian reserves in females. Differences from baseline values were used to identify compromised fertility. Amongst males, HU treatment negatively impacted the concentration of spermatozoa (MD = -15.48 million\/mL; 95% CI: [-20.69, -10.26]; p&lt; 0.001), which continued following treatment cessation (MD = -20.09 million\/mL; 95% CI: [-38.78, -1.40]; P = 0.04). HU treatment also led to lower total sperm counts (MD = -105.87 million; 95% CI: [-140.61, -71.13]; P&lt; 0.001) which persisted after treatment (MD = -53.05 million; 95% CI: [-104.96, -1.14]; P = 0.05). Sperm volume, initial forward motility and morphology were unaffected by HU treatment. In females, HU treatment decreased the mean AMH levels 1.83 (95% CI [1.42, 2.56]. A total of 18.2.% patients treated with HU showed reduced ovarian reserves.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Interpretation &amp; conclusions<\/jats:title>\n<jats:p>This systemic review and meta-analysis suggest that the use of HU for SCD impacts seminal fluid parameters in males and can diminish AMH levels and ovarian reserves in females.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0304241","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T18:12:01Z","timestamp":1717783921000},"page":"e0304241","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Effects of hydroxyurea on fertility in male and female sickle cell disease patients. A systemic review and meta-analysis"],"prefix":"10.1371","volume":"19","author":[{"given":"Sarah","family":"Sewaralthahab","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lujain A.","family":"Alsubki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maram S.","family":"Alhrabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5577-3228","authenticated-orcid":true,"given":"Abdulrahman","family":"Alsultan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"key":"pone.0304241.ref001","doi-asserted-by":"crossref","first-page":"18010","DOI":"10.1038\/nrdp.2018.10","article-title":"Sickle cell disease","volume":"4","author":"GJ Kato","year":"2018","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"pone.0304241.ref002","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1001\/jama.2022.10233","article-title":"Sickle Cell Disease: A Review.","volume":"328","author":"PL Kavanagh","year":"2022","journal-title":"JAMA"},{"issue":"7","key":"pone.0304241.ref003","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1182\/blood-2015-09-618538","article-title":"Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology","volume":"127","author":"D Zhang","year":"2016","journal-title":"Blood"},{"key":"pone.0304241.ref004","volume-title":"UpToDate","author":"M. 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