Evaluating Sperm DNA Damage: When and Why It Does Not Add to the Evaluation of Male Factor Infertility

Male infertility accounts for nearly half of all infertility cases, yet standard semen analysis often fails to reflect sperm's functional competence or fertilization potential. Sperm DNA fragmentation (SDF) has emerged as a potential biomarker of sperm quality, with elevated levels frequently associated with reduced fertilization rates, lower IVF/ICSI success, and an increased risk of recurrent pregnancy loss (RPL). Meta-analyses suggest an inverse relationship between SDF and both clinical pregnancy and live birth rates, particularly in IVF/ICSI cycles; however, assay variability limits the interpretability of SDF testing. Varicocele has been implicated as a contributor to elevated SDF, with several studies indicating an association. However, causality and clinical implications remain under investigation. While varicocelectomy may reduce SDF, its effect on reproductive outcomes remains uncertain. Adjunctive strategies, such as antioxidant therapy, microfluidic sperm selection, and testicular sperm retrieval, have been explored in cases of elevated SDF; however, supporting evidence remains limited. A shortened ejaculatory abstinence interval, typically 24 h or less, has been proposed as a non-invasive strategy to reduce SDF, though its efficacy remains to be fully elucidated. The American Urological Association (AUA) regards SDF testing as investigational. While the AUA discourages its routine use, it permits consideration in select cases, such as RPL or unexplained IVF/ICSI failure. Due to methodological inconsistencies and the lack of standardized thresholds, SDF testing is best applied within an individualized, evidence-informed clinical framework.