Abstract
BACKGROUND: Sperm DNA fragmentation (SDF) is recognized as a leading cause of male infertility because it can impair the paternal genome through distinct pathophysiological mechanisms. Current evidence supports SDF as a major factor in the pathophysiology of several conditions, including varicocele, unexplained infertility, assisted reproductive technology failure, and environmental lifestyle factors, although the mechanisms involved have not been fully described yet. Measurement of the levels of DNA fragmentation in semen provides valuable information on the integrity of paternal chromatin and may guide therapeutic strategies. A recently published clinical practice guideline (CPG) highlighted how to use the information provided by SDF testing in daily practice, which triggered a series of commentaries by leading infertility experts. These commentaries contained an abundance of information and conflicting views about the clinical utility of SDF testing, which underline the complex nature of SDF. METHODS: A search of papers published in response to the CPG entitled "Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios" was performed within the Translational Andrology and Urology (TAU) website (http://tau.amegroups.com/). The start and end dates for the search were May 2017 and August 2017, respectively. Each commentary meeting our inclusion criteria was rated as "supportive without reservation", "supportive with reservation", "not supportive" or "neutral". We recorded whether articles discussed either SDF characteristics as a laboratory test method or clinical scenarios, or both. Subsequently, we extracted the particulars from each commentary and utilized the 'Strengths-Weaknesses-Opportunities-Threats' (SWOT) analysis to understand the perceived advantages and drawbacks of SDF as a specialized sperm function method in clinical practice. RESULTS: Fifty-eight fertility experts from six continents and twenty-two countries contributed commentaries. Overall, participants (87.9%; n=51) were supportive of the recommendations provided by the CPG on the utility of SDF testing based on clinical scenarios. The majority of participants made explicit remarks about both the clinical scenarios and SDF assays' characteristics. Among 'not supportive' and 'supportive with reservation' participants, 75% (n=30/40) and 77.5% (n=31/40) expressed concerns related to technical limitations of SDF testing methods and clinical utility of the test in one or more clinical scenarios discussed in the CPG, respectively. The SWOT analysis revealed that the CPG provides a reasonable evidence-based proposal for integration of SDF testing in the routine daily practice. It also uncovered gaps of knowledge and threats limiting the widespread application of SDF in everyday practice, thus allowing the identification of opportunities to further refine SDF testing and its clinical utility. CONCLUSIONS: The understanding of the role of SDF in male infertility requires an in-depth analysis of the multifactorial pathophysiological processes and the theories involved. The SWOT analysis allowed an objective evaluation of CPG on the clinical utility of SDF testing based on clinical scenarios and its accompanying commentaries written by global experts in all possible angles. Implementation of SDF testing in the clinic may not only increase the outcome of ART but more importantly improve the health of both fathers to be and resulting offspring.