Unpacking the mysteries of sperm DNA fragmentation

Although it has been thirty years since publication of one of the most influential papers on the value of assessing sperm DNA damage, andrologists have yet to reach a general consensus about how to apply this seminal parameter to improve or predict reproductive outcomes. Studies that have attempted to establish a causal relationship between sperm DNA damage and pregnancy success have often resulted in conflicting findings, eroding the practitioner’s confidence to incorporate this phenomenon into their appraisal of fertility. In this review we have identified and answered ten important unresolved questions commonly asked by andrologists with respect to the relationship between sperm DNA damage and fertility. We answer questions ranging from a basic comprehension of biological mechanisms and external factors that contribute to increased levels of sperm DNA damage in the ejaculate to what type of DNA lesions we might be expect to occur and what are some of the consequences of DNA damage on early embryonic development. We also address some of the fundamental technical issues associated with the most appropriate measurement of sperm DNA damage and the need to attenuate the confounding impacts of iatrogenic damage. We conclude by asking whether it is possible to reduce elevated levels of sperm DNA damage therapeutically.