Sperm DNA Fragmentation: A Critical Assessment of Clinical Practice Guidelines

CAPSULE: This review compares and contrasts two independently published guidelines looking at sperm DNA fragmentation (SDF) testing and management of SDF for infertile couples. SDF has been associated with negative reproductive outcomes. Despite the mounting evidence in the literature, there is no consensus for SDF testing and management to assist infertile couples from our infertility societies. In fact, there have been conflicting recommendations from the European Society of Human Reproduction and Embryology (ESHRE), the European Academy of Andrology (EAA), the European Association of Urology (EAU), American Urological Association (AUA), and American Society for Reproduction (ASRM). Agarwal et al (2020) and Esteves et al (2020) separately published guidelines providing recommendations for SDF testing indications, appropriate assays, and management options. This article compared the recommendations from each guideline and sought to provide a combined consensus clinical practice guideline for infertility providers. Finally, the article summarized both guidelines in a well-designed table. The Venn diagram below shows unique and overlapping areas in the three main domains that were analyzed in the article. Despite some differences between the two guidelines, together, they provide extensive complementary evidence for the testing and treatment of SDF in infertile men. The 4 main assays (TUNEL, Comet, SCSA, and SCD) can provide valid and reliable SDF levels. Indications for testing include UMI or IMI, recurrent pregnancy loss, clinical varicocele, lifestyle risk factors, and for before or after failure of ART, including IUI and IVF. Management of elevated SDF includes lifestyle advice and modification, treatment of underlying conditions including varicocele or infection, use of ICSI in cases of persistently elevated SDF, and use of testicular sperm for failed ICSI. With the mounting evidence being provided by independent researchers, hopefully this will move our societies to provide consensus guidelines for testing and management of elevated SDF.

Acknowledgment: Edmund Ko, MD (Los Angeles, USA), Wael Zohdy, MD (Cairo, Egypt; currently in Mississauga, Canada), and Ashok Agarwal (Cleveland, USA) contributed to this week’s management special