Sperm DNA fragmentation: indication and uses

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. If you really think about it, the microscopic portion of conventional sperm analysis relies on the same principles of light microscopy that have been present since Antony van Leeuwenhoek first saw sperm cells in the 17th century. Cell counts, motility, and cellular beauty (based on our idea of an ideal sperm) guide us on a daily basis. Sperm DNA fragmentation testing, represents our best attempt at getting beyond the limits of light microscopy (especially with the wane of sperm functional tests in the era of IVF-ICSI), and that is indicated by the explosion of research into the topic. Agarwal and co-authors (1) expertly update us on the biological rationale and the strengths and weaknesses in the myriad of sperm DNA fragmentation tests that are available. They further go on to review common clinical scenarios and discuss evidenced-based implications of sperm DNA fragmentation testing in those situations. They provide a wonderful framework for which to consider SDF testing in clinical practice in a number of scenarios: (I) SDF testing may help better select varicocelectomy candidates among men with borderline or normal semen analysis parameters; (II) SDF may provide a possible explanation in couples with unexplained infertility or recurrent pregnancy loss or intrauterine insemination failures; (III) SDF may help provide prognostic information in couples that have failed IVF or IVF/ICSI. Additionally, high SDF may be a reason to consider using testicular sperm rather than ejaculated sperm with IVF; (IV) Abnormal SDF results may help those with environmental exposure, occupational exposure or lifestyle risks factors because any abnormality may reinforce the importance of lifestyle modification and exposure minimization. These are all important points and certainly conventional semen analysis parameters are able to shed little light into these scenarios. Yet despite the benefits of SDF testing, the application of SDF testing in these scenarios is not without its limitations, and certainly some of the benefits discussed above can clearly be debated. Specifically in scenario 1 (men with clinical varicoceles and normal or borderline semen analyses), the critical assumption is that SDF provides more information because SDF represents an independent marker of sperm quality independent of conventional semen analysis parameters. This is an area of active research, and the data is mixed at best (2). In scenario 2 (with unexplained infertility or recurrent pregnancy loss or insemination failures), providing any kind of information for unexplained infertility or in recurrent pregnancy loss or IUI failures represents an improvement in care. However, while varicocelectomy studies have shown improvements in SDF after varicocelectomy, the amount of improvement is moderate at best (3). As such if there is poor SDF, do we really have good tools to lower it a significant amount? In cases with normal SDF or mildly elevated SDF, certainly varicocelectomy may help in those patients with clinically palpable varicoceles. In cases with severe SDF, varicocelectomy may not help enough, and couples who undergo varicocelectomy but don’t get pregnant have been found to have higher SDF (4). In scenario 3 (couples who have failed IVF using Commentary