Sperm DNA Fragmentation in Male Infertility: Tests, Mechanisms, Meaning and Sperm Population to Be Tested.

Sperm DNA fragmentation (sDF) is a DNA damage able to predict natural conception. Thus, many laboratories added tests for the detection of sDF as an adjunct to routine semen analysis with specific indications. However, some points related to sDF are still open. The available tests are very different each from other, and a direct comparison, in terms of the prediction of reproductive outcomes, is mandatory. The proposed mechanisms responsible for sDF generation have not yielded treatments for men with high levels of sDF that have gained the general consent in clinical practice, thus requiring further research. Another relevant point is the biological meaning to attribute to sDF and, thus, what we can expect from tests detecting sDF for the diagnosis of male infertility. SDF can represent the "tip of iceberg" of a more extended and undetected sperm abnormality somehow impacting upon reproduction. Investigating the nature of such a sperm abnormality might provide novel insights into the link between sDF and reproduction. Finally, several studies reported an impact of native sDF on assisted reproduction technique outcomes. However, to fertilise the oocyte, selected spermatozoa are used where sDF, if present, associates with highly motile spermatozoa, which is the opposite situation to native semen, where most sDF associates with non-viable spermatozoa. Studies comparing the impact of sDF, as assessed in both native and selected spermatozoa, are needed.