Male Infertility – Genetic Screening

Genetic abnormalities may cause infertility by affecting sperm production and/or transport. The three most common genetic factors known to be related to male infertility are cystic fibrosis gene mutations associated with CBAVD, chromosomial abnormalities resulting in impaired testicular function, and Y-chromosome microdeletions associated with impaired spermatogenesis. Azoospermia and severe oligospermia (sperm concentration < 5 million/mL) are more often associated with genetic abnormalities.
Men with nonobstructive azoospermia and severe oligospermia should be informed that they might have chromosomal abnormalities or Y-chromosome microdeletions. Genetic counseling should be offered whenever a genetic abnormality is found.

Cystic Fibrosis Gene Mutations

The most common cause of CBAVD is a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
It is recommended that both partners undergo genetic counseling and testing of the CFTR gene to rule out abnormalities. Failure to identify a CFTR abnormality in a man with CBAVD, however, does not absolutely rule out the presence of a mutation, since many are undetectable by routine testing methods. It is important to test the partner for CFTR gene abnormalities prior to performing a treatment that utilizes his sperm because of the risk that she may be a carrier.

Karyotype

Karyotype should be ordered in men with severe oligospermia (sperm concentration <5 million/mL)and azoospermia. Paternal transmission of chromosome defects can result in pregnany loss, birth defects, male infertility and other syndromes.

Y-Chromosome Microdeletions

Y-chromosome microdeletions responsible for infertility (azoospermic factor AZF) are detected using sequence tagged sites. The couple must be counseled on the transmission of the gene to all offspring.