Male-factor infertility contributes significantly to the burden of infertility. Fortunately, many causes of male-factor infertility are amenable to surgical intervention. These interventions can be grouped broadly into three categories: 1) those that improve sperm delivery, including vasovasostomy, vasoepididymostomy, and transurethral resection of the ejaculatory ducts, for obstruction of the vas deferens, epididymitis, and ejaculatory ducts, respectively; 2) those that improve testicular function and optimize spermatogenesis, namely varicocelectomy; and 3) those that enable direct retrieval of sperm from either the epididymis (microsurgical epididymal sperm aspiration and percutaneous epididymal sperm aspiration) or testicle (testicular sperm aspiration and testicular sperm extraction). When used in conjunction with other assisted reproductive techniques, including IVF/ICSI, these surgical procedures have vastly improved the reproductive outlook for many subgroups of infertile men who had previous been considered completely infertile.

Patients with azoospermia were once considered to be infertile, with few treatment options. A number of sperm retrieval methods have been developed to obtain spermatozoa from the epididymis and testicles of azoospermic men. This chapter addresses methods for enhancing surgical sperm retrieval and highlights the techniques, imaging modalities, medical therapies, and additional procedures that have led to this increased success.

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.

There are a variety of management options for male infertility patients. Often, assisted reproductive technology allows for successful pregnancies and live births using an ejaculated semen sample. If the etiology of the infertility precludes a satisfactory ejaculated semen sample, sperm retrieval may be required. Determining if a patient is a candidate for sperm retrieval involves a thorough history and physical exam, semen analysis, endocrine evaluation and, likely, genetic assessment. Men who are candidates for sperm retrieval may be azoospermic or anejaculatory. Understanding the etiology of azoospermia is critical to determining the most effective sperm retrieval approach.

Testicular histopathology has been found to be the most reliable predictive factor of successful sperm retrieval in nonobstructive azoospermia patients. Some studies have proposed performing a diagnostic biopsy before assisted reproductive technology. However, its application in clinical practice has been debated due to some criticisms, including its cost-ineffective nature. Another important advantage of histopathology is the revealing of germ cell neoplasia in situ, which occurs in 1–3 percent of infertile patients. Testicular histopathology also offers important information in cases of failed sperm retrieval. When areas of active spermatogenesis are found, the histological pattern could guide the clinician in choosing the more suitable therapeutic option.

All sperm accrue varying amounts of DNA damage during maturation and storage, a process that appears to be mediated through oxidative stress. The clinical significance of genetic damage in the male germ line depends upon severity and how that damage is distributed among the sperm population. In human reproduction, the embryo is capable of significant DNA repair, which occurs prior to the first cleavage event. However, when the magnitude of genomic damage reaches pathologic levels, reproductive outcomes begin to be affected. Evidence now exists linking excessive sperm DNA fragmentation with time to pregnancy for natural conception, pregnancy outcomes of intrauterine insemination and in vitro fertilization, and miscarriage rates when intracytoplasmic sperm injection is employed. This review will discuss the pathophysiology of sperm DNA damage, the studies linking it to impaired reproductive outcomes, and how clinicians may render treatment to optimize the chance of paternity for their patients.