Over the last decade it has become increasingly clear that semen analysis is insufficient to diagnose male infertility. With 30% of infertile men diagnosed as idiopathic, the ethics of continuing to rely on outdated diagnostic parameters must be questioned. Sperm DNA damage is a strong biomarker of male infertility. It also correlates significantly with increased risk of miscarriage after both natural and ART conception. Thirdly, sperm DNA damage is a useful predictive tool for both IVF and ICSI live birth success. DNA fragmentation can occur as double or single strand breaks. Oxidative stress is a common cause of single strand breaks and can be prevented by endogenous and dietary supplemented antioxidants. In contrast, double strand breaks are caused by dysfunction during spermatogenesis, and are harder for oocytes to repair post fertilization. Greater awareness of the relevance of DNA damage and its origins could aid fertility choices and outcomes.

Paternal age is increasing with time. Increasing evidence suggests that a man’s reproductive health changes with age. A man’s fertility may decline as he ages with evidence of an association with unassisted and assisted conception. In addition, there are risks to the pregnancy and child for older fathers. While the definition of advanced paternal age remains uncertain, the consequences of paternal age are becoming more quantifiable.

Over the past 20 years, there has been growing interest in understanding the genomic integrity of human spermatozoa and the clinical relevance of sperm chromatin and DNA defects. We have learned that the etiology of human sperm DNA damage is multi-factorial and that sperm DNA defects are associated with abnormal semen parameters. While we have observed that tests of sperm DNA integrity are correlated with reproductive outcomes, use of these complementary biomarkers in the management of male infertility remains controversial. In this chapter, we review the etiologic factors associated with sperm DNA damage and the utility of these tests in clinical practice. We also review the treatment options for infertile men with sperm DNA damage.