{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:44:58Z","timestamp":1791647098554,"version":"4.3.4"},"reference-count":102,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Recurrent pregnancy loss (RPL) affects numerous couples worldwide and has traditionally been attributed mainly to maternal factors. However, recent evidence highlights significant paternal influences on pregnancy viability and outcomes. This review aims to comprehensively examine male contributions to pregnancy loss, focusing on underlying mechanisms, novel biomarkers, and integrated strategies for improved reproductive success. Materials and Methods: A comprehensive narrative review was conducted by searching databases including PubMed and Embase for the literature published from January 2004 to October 2024. Studies focusing on paternal influences in RPL\u2014encompassing oxidative stress, genetic and epigenetic mechanisms, health conditions, lifestyle factors, environmental exposures, and advancements in sperm proteomics\u2014were included. Inclusion criteria were peer-reviewed articles in English that directly addressed paternal factors in RPL; studies not meeting these criteria were excluded. Results: The review identified that paternal factors such as advanced age, metabolic and cardiovascular health issues, chronic diseases, lifestyle habits (e.g., smoking, alcohol consumption, poor diet), and environmental exposures significantly affect sperm integrity through mechanisms like oxidative stress, DNA fragmentation, and epigenetic alterations. Advanced paternal age and poor health conditions are associated with increased risks of miscarriage and adverse pregnancy outcomes. Novel sperm proteomic biomarkers have been identified, offering potential for enhanced diagnostics and personalized interventions. Integrated approaches involving multidisciplinary assessments, preventive strategies, and genetic counseling are essential for effectively addressing RPL. Conclusions: Integrating paternal factors into clinical evaluations is crucial for effectively addressing recurrent pregnancy loss. Recognizing and modifying paternal risk factors through lifestyle changes, medical interventions, and environmental management can improve pregnancy outcomes. The findings underscore the need for incorporating paternal assessments into standard care and highlight the importance of future research focusing on standardizing diagnostic protocols, expanding studies on paternal contributions, and integrating proteomic biomarkers into clinical practice to facilitate personalized treatment strategies.<\/jats:p>","DOI":"10.3390\/medicina60121920","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T06:41:48Z","timestamp":1732257708000},"page":"1920","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Paternal Contributions to Recurrent Pregnancy Loss: Mechanisms, Biomarkers, and Therapeutic Approaches"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4651-312X","authenticated-orcid":false,"given":"Aris","family":"Kaltsas","sequence":"first","affiliation":[{"name":"Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Zikopoulos","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Royal Cornwall Hospital, Truro TR1 3LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Kojovic","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1198-9144","authenticated-orcid":false,"given":"Fotios","family":"Dimitriadis","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Sofikitis","sequence":"additional","affiliation":[{"name":"Laboratory of Spermatology, Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-005X","authenticated-orcid":false,"given":"Michael","family":"Chrisofos","sequence":"additional","affiliation":[{"name":"Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5287-4450","authenticated-orcid":false,"given":"Athanasios","family":"Zachariou","sequence":"additional","affiliation":[{"name":"Laboratory of Spermatology, Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Muncey, W., Scott, M., Lathi, R.B., and Eisenberg, M.L. 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