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In the 1940s the uniqueness of the spermatozoa protein complex which stabilizes the <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> was discovered. In the fifties and sixties, the association between unstable chromatin structure and subfertility was investigated. In the seventies, the impact of induced <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> damage was investigated. In the 1980s the concept of sperm <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> fragmentation as related to infertility was introduced as well as the first <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> fragmentation test: the Sperm Chromatin Structure Assay (<jats:styled-content style=\"fixed-case\">SCSA<\/jats:styled-content>). The terminal deoxynucleotidyl transferase nick end labelling (<jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content>) test followed by others was introduced in the nineties. The association between <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> fragmentation in spermatozoa and pregnancy loss has been extensively investigated spurring the need for a therapeutic tool for these patients. This gave rise to an increased interest in the aetiology of <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> damage. The present decade continues within this research area. Some of the more novel methods recently submerging are sorting of cells with increased <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> fragmentation and hyaluronic acid (<jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>) binding techniques. The clinical value of these tests remains to be elucidated. In spite of half a century of research within the area, this analysis is not routinely implemented into the fertility clinics. The underlying causes are multiple. The abundance of methods has impeded the need for a clinical significant threshold. One of the most promising methods was commercialized in 2005 and has been reserved for larger licensed laboratories. Myriads of reviews and meta\u2010analyses on studies using different assays for analysis of <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> fragmentation, different clinical Artificial Reproductive Treatments (<jats:styled-content style=\"fixed-case\">ART<\/jats:styled-content>), different definitions of successful <jats:styled-content style=\"fixed-case\">ART<\/jats:styled-content> outcome and small patient cohorts have been published. Although the area of <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> fragmentation in spermatozoa is highly relevant in the fertility clinics, the need for further studies focusing on standardization of the methods and clinical implementation persists.<\/jats:p>","DOI":"10.1111\/andr.12381","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T12:25:49Z","timestamp":1500380749000},"page":"622-630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["DNA fragmentation in spermatozoa: a historical review"],"prefix":"10.1111","volume":"5","author":[{"given":"A. 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