Pretesticular azoospermia is relatively rare and results from gonadotropin deficiency, which leads to loss of spermatogenesis. The physician should perform a full endocrine history that includes information on puberty and growth and check for low serum levels of LH, FSH, and testosterone (44,47,86). Prolactin levels and pituitary imaging are indicated in cases of hypogonadotropic hypogonadism (47). Hormonal treatment includes pulsatile gonadotropinreleasing hormone (GnRH), human chorionic gonadotropin, and exogenous gonadotropins (44,47,86). The best predictors of good response are postpubertal onset of gonadotropin deficiency and testicular volume greater than 8 mL (47).
Gonadal failure is the hallmark of testicular azoospermia. Causes of this condition may be genetic, acquired (e.g., radiation therapy, chemotherapy, testicular torsion, varicocele, or mumps orchitis), or developmental (e.g., testicular maldescent). Testicular atrophy is often present. Because of the low chance of obtaining sperm, testicular biopsy is generally not recommended with hypergonadotropic hypogonadism (elevated levels of LH and FSH with low serum levels of testosterone) and consideration should be given to using donor sperm. Diagnostic testicular biopsies may be indicated in the setting of normal hormonal testing. If sperm are present on diagnostic testing, consideration can be given to using surgically retrieved spermatozoa for ICSI (44,47,86). If no sperm are present, consideration can be given to correcting acquired conditions such as varicocele, which may restore sperm to the ejaculate to permit ICSI or spontaneous pregnancy (87,88). Chromosomal abnormalities by peripheral karyotype testing are present in about 7% of infertile, 5% of oligospermic, and 10% to 15% in azoospermic men. Sex chromosome aneuploidies such as Klinefelter syndrome (47,XXY) encompass two-thirds of these infertility-associated chromosome abnormalities. Microdeletions in the Y chromosome have been identified in 10% to 20% of men with idiopathic azoospermia or severe oligospermia with concentration less than 5 million/mL (44,47,86) (Table 32.6). These microdeletions can be transmitted to the male offspring, who may then suffer from infertility. Therefore, screening for genetic causes is indicated in nonacquired cases of testicular azoospermia so that genetic counseling can be provided before treatment (80). The two most commonly implicated candidate gene families are the RNA-binding motif (RBM) and the “deleted in azoospermia” (DAZ) families, but microdeletions at various loci on the Y chromosome have been described (44,47,86,89–91). For example, microdeletions in Yq11.23 can occur in one or more of three regions: AZFa (proximal), AZFb (central), and AZFc (distal) (44,47,86).