Sperm DNA damage and its impact on male reproductive health: a critical review for clinicians, reproductive professionals and researchers

Introduction: Sperm DNA damage is the major molecular cause of male infertility, which has a negative effect on reproductive outcomes in couples. Sperm DNA damage originates either during production/maturation or transport of spermatozoa through male genital tract. Though several assays have been used to assess the sperm chromatin integrity and sperm DNA fragmentation (SDF), routine application of SDF testing in semen analysis is generally not reinforced by professional societies. SDF testing is now emerging as a valuable tool and recent clinical practice guidelines (CPG) published by the Society for Translational Medicine recommends SDF testing in various clinical scenarios.Areas covered: This review discusses the origin and factors contributing to sperm DNA damage, the molecular changes, especially proteomic alterations caused due to SDF, risk factors associated with SDF, methods used to analyze SDF, clinical implications of SDF, and CPG recommendations for SDF testing.Expert opinion: Recent clinical practice recommendations suggest the potential role of SDF testing in specific clinical scenarios. This would expand the horizon of SDF testing globally as a prognostic and diagnostic tool in various male infertility scenarios and their treatment management.