DNA fragmentation in spermatozoa: a historical review

Sperm DNA Fragmentation has been extensively studied for more than a decade. In the 1940s the uniqueness of the spermatozoa protein complex which stabilizes the DNA was discovered. In the fifties and sixties, the association between unstable chromatin structure and subfertility was investigated. In the seventies, the impact of induced DNA damage was investigated. In the 1980s the concept of sperm DNA fragmentation as related to infertility was introduced as well as the first DNA fragmentation test: the Sperm Chromatin Structure Assay (SCSA). The terminal deoxynucleotidyl transferase nick end labelling (TUNEL) test followed by others was introduced in the nineties. The association between DNA 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 DNA damage. The present decade continues within this research area. Some of the more novel methods recently submerging are sorting of cells with increased DNA fragmentation and hyaluronic acid (HA) 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‐analyses on studies using different assays for analysis of DNA fragmentation, different clinical Artificial Reproductive Treatments (ART), different definitions of successful ART outcome and small patient cohorts have been published. Although the area of DNA 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.