{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:06:29Z","timestamp":1789383989844,"version":"build-2803163510"},"reference-count":74,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:00:00Z","timestamp":1590710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several cellular insults can result in sperm DNA fragmentation either on one or both DNA strands. Oxidative damage, premature interruption of the apoptotic process and defects in DNA compaction during spermatogenesis are the main mechanisms that cause DNA breaks in sperm. The two-tailed Comet assay is the only technique that can differentiate single- (SSBs) from double- (DSBs) strand DNA breaks. Increased levels of the phosphorylated isoform of the H2AX histone are directly correlated with DSBs and proposed as a molecular biomarker of DSBs. We have carried out a narrative review on the etiologies associated with SSBs and DSBs in sperm DNA, their association with reproductive outcomes and the mechanisms involved in their repair. Evidence suggests a stronger negative impact of DSBs on reproductive outcomes (fertilization, implantation, miscarriage, pregnancy, and live birth rates) than SSBs, which can be partially overcome by using intracytoplasmic sperm injection (ICSI). In sperm, SSBs are irreversible, whereas DSBs can be repaired by homologous recombination, non-homologous end joining (NHEJ) and alternative NHEJ pathways. Although few studies have been published, further research is warranted to provide a better understanding of the differential effects of sperm SSBs and DSBs on reproductive outcomes as well as the prognostic relevance of DNA breaks discrimination in clinical practice.<\/jats:p>","DOI":"10.3390\/ijms21113882","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T04:09:03Z","timestamp":1591070943000},"page":"3882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["The Impact of Single- and Double-Strand DNA Breaks in Human Spermatozoa on Assisted Reproduction"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0585-1026","authenticated-orcid":false,"given":"Ashok","family":"Agarwal","sequence":"first","affiliation":[{"name":"American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2854-9834","authenticated-orcid":false,"given":"C\u0103t\u0103lina","family":"Barb\u0103ro\u0219ie","sequence":"additional","affiliation":[{"name":"American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Department of Genetics, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3496-2895","authenticated-orcid":false,"given":"Rafael","family":"Ambar","sequence":"additional","affiliation":[{"name":"American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Urology Department of Centro Universitario em Saude do ABC\/Andrology Group at Ideia Fertil Institute of Human Reproduction, 09015 Santo Andr\u00e9, Brazil"},{"name":"Hope Clinic\u2014Human Reproduction, 09060-650 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5926-6407","authenticated-orcid":false,"given":"Renata","family":"Finelli","sequence":"additional","affiliation":[{"name":"American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1093\/molehr\/gap080","article-title":"Function of sperm chromatin structural elements in fertilization and development","volume":"16","author":"Ward","year":"2009","journal-title":"Mol. 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