Depending upon the patient’s clinical presentation, genetic testing may be required for diagnostic and prognostic purposes. The tests include karyotyping, testing for Y-chromosome microdeletions and for cystic fibrosis related (CFTR) mutations. 

The introduction of assisted reproduction techniques such as ICSI have made it possible for men with severe oligozoospermia (low count) and azoospermia (no sperm in the ejaculate) to father children. However there are genetic risks associated with these invasive techniques that need to be considered. These include the risks of transferring the CFTR gene, somatic and sex chromosome abnormalities, microdeletions of the Y chromosome and X-chromosome defects.

Chromosomal anomalies

Karyotyping is recommended for men with elevated serum FSH and LH concentrations and a sperm concentration less than 10 million/mL. Chromosomal translocations are much more common in infertile men than fertile men and occur in up to 15 percent of men with severe oligozoospermia or azoospermia Klinefelter syndrome is the most common congenital abnormality causing primary hypogonadism, occurring in approximately 1 in 1000 live male births. These men typically have small, firm testes as well as skeletal and psycho-social manifestations. 

Y-chromosome microdeletions, X-chromosome defects, and epigenetics

Approximately 10 to 18 percent of men with sperm concentrations less than 5 million/mL have microdeletions of the Y chromosome. These Y-chromosome deletions (and risk of male infertility) may be transmitted from father to son by ICSI. Testing for microdeletion of the Y chromosome should be offered to men with sperm concentrations ≤5million/mL.

CFTR gene 

Men with cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations may present with obstructive azoospermia with or without manifestations of cystic fibrosis. They often have a normal testicular volume; no vas deferens on palpation of the external genitalia; and normal serum LH, FSH, and testosterone concentrations. In this setting, a family history of cystic fibrosis should be obtained, and both the male and female partner should be tested for CFTR gene mutations.