{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T05:59:01Z","timestamp":1781330341415,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"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>Introduction<\/jats:title>\n                    <jats:p>Male infertility is increasingly recognized as a systemic condition associated with impaired long\u2010term health, yet clinically applicable frameworks linking reproductive dysfunction to comorbidity burden remain limited. Here, we investigated whether a composite immuno\u2010metabolic signature could capture comorbidity burden and reduced reproductive capacity in men with primary male factor infertility (MFI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Materials<\/jats:title>\n                    <jats:p>In a cross\u2010sectional cohort of 2953 men, metabolic and inflammatory variables were systematically screened for directional and independent associations with comorbidity burden, defined by the Charlson Comorbidity Index (CCI) \u22651, and impaired reproductive capacity, assessed by total motile sperm count (TMSC) &lt;5 million. Three variables\u2010LDL cholesterol, waist circumference, and C\u2010reactive protein (CRP)\u2010met selection criteria and were integrated into an unweighted standardized score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three variables met selection criteria: LDL cholesterol, waist circumference, and C\u2010reactive protein. Higher immuno\u2010metabolic scores were observed in men with comorbidity burden (0.20 \u00b1 0.73 vs. \u22120.02 \u00b1 0.62,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001) and in those with TMSC &lt;5M (0.13 \u00b1 0.64 vs. \u22120.07 \u00b1 0.62,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). Each unit increase in the score was independently associated with comorbidity burden (OR 1.50, 95% CI 1.23\u20131.82,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001) and TMSC &lt;5M (OR 1.67, 95% CI 1.48\u20131.89,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). Predicted probabilities rose across the score range from 2% to 40% for comorbidity and from 12% to 75% for reduced reproductive capacity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings identify a biologically coherent immuno\u2010metabolic signature linking spermatogenic impairment with systemic comorbidity in men with primary MFI and support a model in which male infertility reflects broader immuno\u2010metabolic vulnerability. Prospective external validation is warranted before clinical implementation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70275","type":"journal-article","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T05:47:20Z","timestamp":1781329640000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Profiling Identifies Infertile Men at Risk of Accelerated Aging: Implications for Systemic and Reproductive Health"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0228-7039","authenticated-orcid":false,"given":"Edoardo","family":"Pozzi","sequence":"first","affiliation":[{"name":"Vita\u2010Salute San Raffaele University  Milan Italy"},{"name":"Division of Experimental Oncology\/Unit of Urology URI IRCCS Ospedale San Raffaele  Milan 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