{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T06:13:48Z","timestamp":1779257628354,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Genetic variability within the follicle\u2010stimulating hormone (FSH)\u2010related genes might contribute to phenotypic heterogeneity in patients with Klinefelter syndrome (KS), yet its clinical impact on sperm retrieval remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To investigate the association between\n                      <jats:italic>FSHB<\/jats:italic>\n                      c.211 G &gt; T and\n                      <jats:italic>FSHR<\/jats:italic>\n                      polymorphisms (c.2039 A &gt; G and c.29 G &gt; A) and hormonal parameters, as well as their potential role in predicting sperm retrieval rate (SRR) in patients with KS undergoing testicular sperm extraction (TESE).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      A retrospective cohort of patients with KS was analyzed. Only subjects not receiving testosterone replacement therapy were included (\n                      <jats:italic>n<\/jats:italic>\n                      = 417). Hormonal, anthropometric, and clinical variables were compared across genotypes using nonparametric tests. Additive genetic models were applied to evaluate allele\u2010dose effects. Multivariable logistic regression was performed to identify independent predictors of SRR. Predictive performance of clinical and combined clinical\u2013genetic models was assessed using ROC curve analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>FSHB<\/jats:italic>\n                      and\n                      <jats:italic>FSHR<\/jats:italic>\n                      genes polymorphisms were associated with variations in serum FSH concentrations, confirming a modulatory role of the FSH\u2010related genes. In additive modeling, the\n                      <jats:italic>FSHR<\/jats:italic>\n                      c.29 G &gt; A polymorphism emerged as an independent predictor of SRR (adjusted OR: 0.29; 95% CI, 0.09\u20130.97), whereas\n                      <jats:italic>FSHB<\/jats:italic>\n                      c.211 G &gt; T showed a nonsignificant trend. The inclusion of genetic variants modestly improved predictive accuracy compared with clinical variables alone, as demonstrated by ROC analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and Conclusion<\/jats:title>\n                    <jats:p>\n                      Genetic variants within the genes involved in FSH action might contribute incremental information for the prediction of sperm retrieval in patients with KS. While the overall predictive gain remains moderate, additive genetic modeling highlights a potential allele\u2010dose effect of\n                      <jats:italic>FSHR<\/jats:italic>\n                      c.29 G &gt; A on reproductive outcome, supporting a role for integrated clinical\u2013genetic assessment in this population, although external validation remains required.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70262","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:56:33Z","timestamp":1779256593000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of\n                    <i>FSHB<\/i>\n                    and\n                    <i>FSHR<\/i>\n                    Genes Polymorphisms on Hormonal Profile and Sperm Retrieval Outcome in Men With Klinefelter Syndrome: A Clinical\u2013Genetic Predictive Study"],"prefix":"10.1111","author":[{"given":"Andrea","family":"Graziani","sequence":"first","affiliation":[{"name":"Department of Medicine University of Padova  Padova Italy"},{"name":"Unit of Andrology and Reproductive Medicine, Department of Systems Medicine University of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3264-0937","authenticated-orcid":false,"given":"Giuseppe","family":"Grande","sequence":"additional","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine, Department of Systems Medicine University of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Santa","family":"Rocca","sequence":"additional","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine, Department of Systems Medicine University of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Iafrate","sequence":"additional","affiliation":[{"name":"Unit of Urology, Department of Surgery, Oncology and Gastroenterology University Hospital of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Selice","sequence":"additional","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine, Department of Systems Medicine University of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Di Mambro","sequence":"additional","affiliation":[{"name":"Unit of Andrology and Reproductive Medicine, Department of Systems Medicine University of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5817-8141","authenticated-orcid":false,"given":"Alberto","family":"Ferlin","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Padova  Padova Italy"},{"name":"Unit of Andrology and Reproductive Medicine, Department of Systems Medicine University of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12909"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC\u201023\u20100058"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.70033"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpuro0775"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.14310\/horm.2002.1622"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012\u20102382"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnaf005"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.70053"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00047"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dead277"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/den216"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE\u201013\u20100624"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013\u20101294"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.142"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012\u20101761"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17040689"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnaf013"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618\u2010022\u201001859\u20107"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.13217"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12808"},{"key":"e_1_2_10_22_1","volume-title":"WHO Laboratory Manual for the Examination and Processing of Human Semen\u2014Sixth Edition","author":"World Health Organization","year":"2021"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.13504"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/8.10.893"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1472\u20106483(10)61026\u20107"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009\u20101010"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2011.09.034"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew167"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac165"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094244"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.14383"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12949"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12333"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018\u201002249"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmx008"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.70030"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.70262","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/andr.70262","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.70262","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:56:37Z","timestamp":1779256597000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.70262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,19]]},"references-count":35,"alternative-id":["10.1111\/andr.70262"],"URL":"https:\/\/doi.org\/10.1111\/andr.70262","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,19]]},"assertion":[{"value":"2026-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"andr.70262"}}