{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:42:48Z","timestamp":1793133768986,"version":"4.5.0"},"reference-count":148,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sperm DNA fragmentation (SDF) represents strand breaks that may compromise embryo development, reproductive outcomes, and offspring health, particularly when the oocyte\u2019s repair capacity is limited. This mini-review provides a clinically pragmatic framework addressing how to test, when to test, and whom to test for SDF, translating biological and laboratory insights into actionable andrology practice. The mechanistic basis of SDF is summarized, including the two-step hypothesis linking defective chromatin packaging to oxidative stress, and the combined influence of paternal and maternal aging on the creation and repair of DNA lesions. Contemporary methods for detecting both single- and double-strand breaks (DSBs), as well as DSB-specific platforms, are reviewed with emphasis on assay-specific cut-offs and clinical indications. Management strategies are outlined, prioritizing andrological optimization through lifestyle modification, antioxidant supplementation, treatment of genital tract infection, varicocele repair, and selected hormonal therapy, followed by retesting after one spermatogenic cycle. For persistently high SDF, selective use of testicular sperm for ICSI (Testi-ICSI) and laboratory adjuncts is discussed, supported by evidence of lower miscarriage and higher live-birth rates in defined high-SDF phenotypes. The limitations of the existing observational evidence base\u2014particularly the paucity of phenotype-targeted randomized controlled trials\u2014are highlighted. The review also underscores the value of embedding SDF testing within quality-managed programs and incorporating systematic audits of indications, treatment effects, and ART outcomes. Beyond ART, SDF assessment is positioned within preconception care, recognizing sperm chromatin integrity as a determinant of reproductive and intergenerational health. Future priorities include randomized trials comparing testicular and ejaculated sperm for ICSI in high-SDF cohorts, validation of DSB-specific assays, and longitudinal offspring follow-up to clarify intergenerational effects. This integrative approach promotes precision rather than proliferation of testing, aligning molecular insight with clinical prudence to improve reproductive and generational outcomes.<\/jats:p>","DOI":"10.1093\/humrep\/deag056","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T12:57:05Z","timestamp":1773838625000},"page":"1024-1039","source":"Crossref","is-referenced-by-count":8,"title":["Sperm DNA fragmentation: how to test, when to test, and what to do with abnormal results\u2014a pragmatic mini-review for clinical practice"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1313-9680","authenticated-orcid":false,"given":"Sandro C","family":"Esteves","sequence":"first","affiliation":[{"name":"ANDROFERT, Andrology and Human Reproduction Clinic , Campinas, SP,","place":["Brazil"]},{"name":"Department of Surgery (Division of Urology), Faculty of Medical Sciences, University of Campinas (UNICAMP) , Campinas, SP,","place":["Brazil"]},{"name":"Department of Clinical Medicine, Aarhus University , Aarhus,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-5366","authenticated-orcid":false,"given":"Peter","family":"Humaidan","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University , Aarhus,","place":["Denmark"]},{"name":"University Clinic for Fertility, Skive Regional Hospital , Skive,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"2026071706265330300_deag056-B1","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.urology.2016.03.059","article-title":"Abstinence time and its impact on basic and advanced semen parameters","volume":"94","author":"Agarwal","year":"2016","journal-title":"Urology"},{"key":"2026071706265330300_deag056-B2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.rbmo.2022.03.012","article-title":"Role of sperm DNA damage in creating de-novo mutations in human offspring: the \u2018post-meiotic oocyte collusion\u2019 hypothesis","volume":"45","author":"Aitken","year":"2022","journal-title":"Reprod Biomed Online"},{"key":"2026071706265330300_deag056-B3","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1093\/humrep\/dead157","article-title":"Male reproductive ageing: a radical road to ruin","volume":"38","author":"Aitken","year":"2023","journal-title":"Hum Reprod"},{"key":"2026071706265330300_deag056-B4","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1093\/humrep\/deae230","article-title":"Paternal age, de novo mutations, and offspring health? 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