{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:40:26Z","timestamp":1792129226766,"version":"4.4.0"},"reference-count":183,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Oxidative stress (OS) and sperm DNA fragmentation (SDF) are complementary contributors to male infertility. OS characterizes a compromised seminal redox status, whereas SDF quantifies downstream genomic damage. Human sperm are highly susceptible to redox damage due to lipid-rich membranes and disrupted post-meiotic DNA-repair capacity. Excess reactive oxygen species (ROS) can cause lipid peroxidation, oxidative base lesions, and DNA strand breaks that impair fertilization, embryo development, and pregnancy outcomes. This review explains how OS promotes genomic instability and summarizes the main laboratory assays that assess redox status and SDF in semen. These include direct ROS chemiluminescence assay, oxidation\u2013reduction potential, total antioxidant capacity\/ferric reducing antioxidant power, and lipid peroxidation biomarkers, alongside SDF platforms (Sperm Chromatin Structure Assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling, alkaline\/neutral Comet, and sperm chromatin dispersion). Additionally, guideline-aligned indications are highlighted to clarify the conditions for testing OS and SDF. OS testing is most relevant in men with leukocytospermia or suspected genital tract infection or inflammation, including dysbiosis; in cases of major modifiable exposures such as smoking or heat; and for early monitoring after treatment. SDF testing is particularly informative in couples with recurrent pregnancy loss and in unexplained infertility with normal semen parameters. Combined OS and SDF testing is recommended in clinical varicocele, repeated in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) failure, poor embryo development, and follow-up after targeted therapy. Management centers on treating infection and inflammation, improving lifestyle and environmental factors, considering varicocelectomy when indicated, using targeted antioxidant therapy in men with documented OS, and selectively applying sperm selection technologies or testicular sperm for ICSI when SDF remains high. Priorities include assay standardization, etiologic attribution of DNA damage, and trials testing OS\/SDF-guided pathways with live birth as the primary endpoint. When used selectively and in the appropriate context, OS and SDF testing can help refine diagnosis, improve counseling, and help personalize care of infertile couples.<\/jats:p>","DOI":"10.3390\/antiox15030293","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T16:57:13Z","timestamp":1772125033000},"page":"293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Oxidative Stress, Sperm DNA Fragmentation, or Both? Optimizing Test Selection in Male Infertility Evaluation"],"prefix":"10.3390","volume":"15","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"},{"name":"Global Andrology Forum, Global Andrology Foundation, Moreland Hills, OH 44022, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8333-5134","authenticated-orcid":false,"given":"Stamatis","family":"Papaharitou","sequence":"additional","affiliation":[{"name":"Global Andrology Forum, Global Andrology Foundation, Moreland Hills, OH 44022, USA"},{"name":"Andrology Laboratory and Sperm Bank, 54622 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-5048","authenticated-orcid":false,"given":"Pallav","family":"Sengupta","sequence":"additional","affiliation":[{"name":"Global Andrology Forum, Global Andrology Foundation, Moreland Hills, OH 44022, USA"},{"name":"Department of Biomedical Sciences, College of Medicine, Gulf Medical University, Ajman P.O. Box 4184, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramadan","family":"Saleh","sequence":"additional","affiliation":[{"name":"Global Andrology Forum, Global Andrology Foundation, Moreland Hills, OH 44022, USA"},{"name":"Department of Dermatology, Venereology & Andrology, Faculty of Medicine, Sohag University, Sohag 82524, Egypt"},{"name":"Ajyal IVF Center, Ajyal Hospital, Sohag 82511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Global Andrology Forum, Global Andrology Foundation, Moreland Hills, OH 44022, USA"},{"name":"Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2023). 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