{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T06:36:03Z","timestamp":1792305363003,"version":"4.4.0"},"reference-count":133,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Male infertility is a complex, multifactorial condition influenced by infectious, inflammatory, and autoimmune components. Immunological factors, though implicated in reproduction, remain poorly understood. This study aims to deepen the understanding of infections, inflammation, and autoimmune factors in male infertility, with a focus on immune-related disorders affecting the testes and epididymis\u2014immunologically privileged but vulnerable sites. These factors can impair sperm quality through oxidative stress (ROS) and antisperm antibodies (ASA), further compromising fertility. Methods: A narrative review was conducted by analyzing scientific literature from the past 10 years conducted on PubMed using keywords such as \u201cmale infertility\u201d, \u201cautoimmunity\u201d, and \u201cinflammatory disease\u201d. Studies focusing on testicular and epididymal disorders, immunological impacts, and therapeutic approaches were included. Results: Our research highlights that conditions like epididymitis, vasectomy, testicular trauma, and previous surgeries can trigger inflammatory responses, leading to ASA formation and oxidative stress. ASA, particularly sperm-immobilizing antibodies, inhibits sperm motility and migration in the female reproductive tract. Infections caused by sexually transmitted bacteria or urinary pathogens frequently induce epididymo-orchitis, a primary contributor to male infertility. While standardized methodologies for ASA testing remain elusive, assisted reproductive treatments such as intracytoplasmic sperm injection (ICSI), in vitro fertilization (IVF), and intrauterine insemination (IUI) show promise in overcoming immune-mediated infertility. Conclusions: This review underscores the critical role of infection, inflammation, and autoimmune responses in male infertility. It highlights the necessity of improving diagnostic methods, understanding immune-pathological mechanisms, and addressing medicolegal issues associated with male infertility. This knowledge could pave the way for innovative therapies, ultimately enhancing fertility outcomes, and mitigating the societal and legal repercussions of infertility.<\/jats:p>","DOI":"10.3390\/diagnostics15050547","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T10:52:47Z","timestamp":1740394367000},"page":"547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Decoding the Puzzle of Male Infertility: The Role of Infection, Inflammation, and Autoimmunity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7698-8823","authenticated-orcid":false,"given":"Romualdo","family":"Sciorio","sequence":"first","affiliation":[{"name":"Fertility Medicine and Gynecological Endocrinology Unit, Department Woman Mother Child, Lausanne University Hospital, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4631-1061","authenticated-orcid":false,"given":"Lina","family":"De Paola","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Notari","sequence":"additional","affiliation":[{"name":"Check-Up Poly-Diagnostic and Research Laboratory, Andrology Unit, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Ganduscio","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, IVF UNIT-AOOR Villa Sofia\u2014Cervello, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Amato","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, ASL Salerno, 60th District, 84124 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Crifasi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, IVF UNIT-AOOR Villa Sofia\u2014Cervello, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Marotto","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, ASL Gallura, 07026 Olbia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Billone","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, IVF UNIT-AOOR Villa Sofia\u2014Cervello, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaspare","family":"Cucinella","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, IVF UNIT-AOOR Villa Sofia\u2014Cervello, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Perino","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, IVF UNIT-AOOR Villa Sofia\u2014Cervello, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8654-3123","authenticated-orcid":false,"given":"Luca","family":"Tramontano","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Gyn\u00e9cologie-Obst\u00e9trique, R\u00e9seau Hospitalier Neuch\u00e2telois, 2000 Neuch\u00e2tel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Marinelli","sequence":"additional","affiliation":[{"name":"School of Law, Polytechnic University of Marche, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4269-4269","authenticated-orcid":false,"given":"Giuseppe","family":"Gullo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, IVF UNIT-AOOR Villa Sofia\u2014Cervello, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1093\/humrep\/dew123","article-title":"Prevalence of Infertility and Help Seeking among 15,000 Women and Men","volume":"31","author":"Datta","year":"2016","journal-title":"Hum. 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