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.

Sperm retrieval and intracytoplasmic sperm injection (ICSI) has become the natural treatment for couples with azoospermia-related infertility, and nowadays is also used for nonazoospermic indications. An increasing body of evidence overwhelmingly based on cohort studies has indicated that ICSI with ejaculated sperm of poor quality negatively affects the chances of assisted conception. Collectively, these data suggest that ICSI with testicular sperm is superior to ICSI with ejaculated sperm as a method of fertilization to overcome sperm DNA fragmentation-related infertility. The candidates are men with high sperm DNA damage in semen and those with severe oligozoospermia or cryptozoospermia. In these patients, percutaneous and open sperm retrieval are highly successful to harvest sperm, with few complications. Current evidence suggests the safe utilization of testicular sperm for ICSI in nonazoospermic men. Further research is warranted to confirm the clinical utility of this approach as a routine ART treatment.