Sperm DNA fragmentation: a key player in decision making

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. We read, with great interest, the commentary written by Wayland Hsaio on the “Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios” (1). The author acknowledges sperm DNA fragmentation as an important addition to conventional methods for assessment of sperm quality highlighting the need for practice guidelines to describe its utility in different clinical scenarios. The author has critically appraised the utility of SDF in varicocele, as a tool to indicate testicular sperm retrieval in patients with recurrent pregnancy loss after intracytoplasmic sperm injection (ICSI) and in patients with lifestyle risk factors. His comments which are probably echoed by many, are indeed legitimate warranting a response aimed to further clarify the appropriate application of SDF for male fertility evaluation. The author’s notion that SDF may be considered as an independent parameter of sperm quality in varicocele patients’ needs further discussion. SDF levels have been negatively correlated with sperm concentration, motility and normal morphology in infertile men regardless of the varicocele status (2). However, it seems true that patients with clinical varicocele and normal semen parameters exhibit significantly higher SDF levels than patients without varicocele (3). Moreover, it has been reported that patients with varicocele have a higher proportion of sperm with ‘massive’ DNA fragmentation, so-called ‘degraded sperm’, than infertile men without varicocele (4). The authors of the study mentioned above have postulated that the overrepresentation of sperm with degraded DNA in the semen is indicative of varicocele. The controversy surrounding the effects of varicocele on male fertility together with the fact that conception rather than improvement in sperm quality is the real sought outcome after varicocelectomy prompted the use of SDF testing in this patient population. Evidence suggests that significant reductions in SDF occur after varicocelectomy, but more importantly, such changes are associated with a higher likelihood of conception (5,6). These findings, coupled with the independent existence of SDF in varicocele patients highlights the clinical utility of SDF testing when selecting patients for surgery (1). The author advised us to be cautious in patients with severe SDF, as varicocelectomy may not be enough to revert sperm DNA integrity to normal levels. He cited the prospective clinical study by Smit et al. which evaluated SDF levels and pregnancy outcomes of 49 men with clinical varicocele who underwent varicocelectomy (7). These authors observed significantly higher SDF levels in patients who failed to conceive after surgery. While we do agree with Dr. Hsiao that in cases with severe SDF, varicocele may not be entirely responsible and hence proper patient counselling before surgery is advised, we actually find the results of Smit et al. to be fully in favor of using SDF during the evaluation of patients with clinical varicocele. In their study, the authors reported a significant decrease in SDF (measured with sperm chromatin structure assay) after surgery from 35.2% to 30.2% (P=0.019). Moreover, out of the included couples in the study, 37% conceived naturally and 24% achieved pregnancy with an assisted reproductive technique (ART) after varicocelectomy. More importantly, SDF levels were significantly lower in those who achieved pregnancy whether naturally or through ART. The authors concluded that “After varicocelectomy sperm parameters significantly improved and sperm DNA fragmentation was Editorial