Is the sperm DNA status the best predictor of both natural and assisted conception?

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. The number of articles on the clinical significance of sperm DNA integrity and/or fragmentation has been increasing during the last 2 decades. Despite substantial evidence, official recommendation to introduce sperm genomic integrity tests into the routine evaluation of ‘male factor’ is lacking. The review by Agarwal and co-authors (1) summarized promising results for clinical utility of sperm DNA fragmentation tests. Based on their own large experience, the authors demonstrated four different cases of infertile men, in which the evaluation of sperm DNA quality can be recommended. Although the study provides useful prognostic information for practitioners who treat infertility, some critical questions remains unresolved. As for sperm DNA fragmentation measurement, variability among the individuals, medical interventions and methodology have been the main cause of conflicting results. In this context, we have “high hopes” associated with the development of new quantitative epidemiological statistical tools providing the opportunity to combine data from the multiple independent studies and to consolidate the conflicting results. In fact, several previous metaanalyses, also from the author’s group, demonstrated some positive clues that sperm with DNA damage may provoke detrimental outcomes of the in vitro fertilization procedures including decreased pregnancy rates and/or increased miscarriages (2-4). However, in contrast to the study by Agarwal and co-authors, other researchers found no association between sperm DNA fragmentation and clinical outcome of medically assisted reproduction using a systematic review and meta-analysis (5). At this point, it should be emphasized that the value of a meta-analysis provides a useful ground for formal recommendations but it does not provide the definitive answer to the question for the future of the assessment of sperm genomic integrity. Randomized controlled trials in the field are still very limited. There is a need to conduct more prospective studies, including large numbers of patients, a wide range of analyzed semen parameters, patient characteristics and a reproductive outcome. The etiology of sperm DNA damage is complex and multifactorial. On the basis of clinical and experimental results, three different molecular and biochemical pathways have been proposed to explain the etiology of sperm DNA fragmentation: complexity of sperm maturation process, incomplete apoptosis in testis and free radical attack (6). There is now increasing evidence that the majority of sperm DNA breaks are of oxidative origin. In this context, the recommendation of Agarwal and co-authors for determining of the level of sperm DNA fragmentation in infertile men with evidence of exposure to environmental and lifestyle factors linked with oxidative stress is well justified (1). However, it is important to remember that the three abovementioned pathogenic mechanisms may contribute in various proportions to the DNA status in sperm arriving to the ejaculate. It is estimated that DNA damage observed in ejaculated spermatozoa may be partially caused by posttesticular defects during sperm transit (7,8). Regardless of these interesting findings, the origin of DNA damage in the male germ line still presents a puzzle. Despite a range of DNA evaluation techniques, none of currently available assays provides reliable information on the nature of sperm DNA breaks and their origin. Without accurate knowledge Commentary