Obstructive azoospermia (OA) is the absence of spermatozoa and spermatogenetic cells in semen and post-ejaculate urine due to obstruction (Fig. 16.5). OA is less common than non-obstructive azoospermia (NOA) and occurs in 15–20% of men with azoospermia. Men with OA present with normal follicle-stimulating hormone (FSH), normal size testes, and epididymal enlargement.

Obstruction in primary infertile men is often present at the epididymal level. Epididymal obstruction is the most common cause of OA, affecting 30–67% of azoospermic men. Congenital epididymal obstruction usually manifests as congenital bilateral absence of the vas deferens (CBAVD), which is associated with at least 1 mutation of the CF gene in 82% of cases. Intratesticular obstruction occurs in 15% of men with OA. Ejaculatory duct obstruction is found in 1–3% of cases of OA and is classified as either cystic or post-inflammatory [9, 10].

Non-obstructive azoospermia (NOA), also referred to as testicular failure, occurs in 49–93% of patients with normal semen ejaculate volume with no sperms (Fig. 16.6). The testicular failure indicates a complete absence of spermatogenesis, but men with testicular failure actually have also either reduced spermatogenesis, maturation arrest, or complete failure of spermatogenesis noted with Sertoli-cell-only syndrome [11, 12]. In men with testicular deficiency, hypergonadotropic hypogonadism is usually present, with high levels of FSH and luteinizing hormone (LH), and sometimes low LH and FSH levels with low or normal levels of testosterone. The levels of FSH correlate with the number of spermatogonia; when spermatogonia are absent or markedly diminished, FSH values are usually elevated. However, for an individual patient, FSH levels do not accurately predict the spermatogenesis status because men with maturation arrest histology could have normal FSH and normal testis volume and still be azoospermic. Testicular biopsy is usually the method of choice to provide definitive diagnosis and also as a part of the treatment option [13–15].

Indications for AZF deletion screening are based on sperm count and include the patient presenting with azoospermia and severe oligozoospermia (spermatozoa count <5 million/mL). The highest frequency of Y-deletions is found in azoospermic men (8–12%), followed by oligozoospermic (3–7%) men [16]. The microdeletion of the Yq chromosome is not indicated in normozoospermic men, proving there is a clear-cut cause-and-effect relationship between Y-deletions and spermatogenic failure [17]. AZFc deletions are most common (65–70%), followed by Y-deletions of the AZFb and AZFb + c or AZFa + b + c regions (25–30%). AZFa region deletions are rare (5%). Complete removal of the AZFa region is associated with severe testicular phenotype (Sertoli-cell-only syndrome), while complete removal of the AZFb region is associated with spermatogenic rest. Complete removal of the AZFc region causes a variable phenotype ranging from azoospermia to oligozoospermia. The specificity and genotype/phenotype correlation reported above means that Y-deletion analysis has both a diagnostic and prognostic value for testicular sperm retrieval [18]. The common genetic investigations required in the workup of infertile patient due to “male factor” with their relative frequency are summarized in Table 16.4.

The most common male coital disorders impacting fertility include erectile dysfunction (impotence), failure of ejaculation (anejeculation), and retrograde ejaculation. These disorders are more common in patients with neurologic diseases and patients with—who desire fertility. These patients face challenges that include hormonal imbalances, ejaculatory dysfunction, and poor semen quality. The list of common clinical challenges encountered in patients with male factors, and their subsequent management, is summarized in Table 16.5 (see also Fig. 16.7).