Infertility is defined as the failure to conceive after a couple attempts to become pregnant for 12 months or more. This panel tests for genetic causes of male infertility due to azoospermia and oligospermia (mild, moderate or severe) including: mosaic chromosome analysis, Y chromosome microdeletion, and CFTR
Approximately 5-10% of males with non-obstructive azoospermia, oligospermia, or other abnormalities of sperm morphology or motility are caused by structural or numerical abnormalities, including Y chromosome microdeletions. Mosaic chromosome analysis is used to detect chromosomal abnormalities including sex chromosome aneuploidies, chromosomal mosaicism, and chromosomal rearrangements. Sex chromosome aneuploidies may include conditions such as Klinefelter syndrome (47,XXY). Chromosomal mosaicism is defined as the presence of two or more cell populations with different chromosomes. Testing for chromosomal mosaicism provides a more thorough chromosome analysis by examining a total of 50 cells (30 additional cell counts). Chromosomal rearrangements that can cause male infertility, including large deletions (deletion of Yq12) or structural abnormalities (including pseudodicentric Y inversions or translocations) are detectable by this assay. Results from chromosome analysis may suggest investigation of other single gene disorders of sex development when the karyotype results are discordant from the phenotypic gender of the patient (such as translocation of SRY
or SOX 9
Approximately 5-10% of males with non-obstructive azoospermia or oligospermia have microdeletions in the AZFa, AZFb, AZFc
regions on the Y chromosome that are not detectable by standard cytogenetic methods. Each AZF
region contains multiple genes that are involved in different stages of spermatogenesis. Most cases of Y chromosome microdeletions are new mutations. If assistive reproductive technologies are used, a male child receiving the Y chromosome will have the microdeletion, and therefore, all sons will be affected.
Cystic fibrosis transmembrane conductance regulator (CFTR
) gene mutations are associated with obstructive azoospermia and oligospermia. Approximately two-thirds of males with congenital bilateral absence of the vas deferens (CBAVD) have mutations of the CFTR
gene. Males with unilateral absence of the vas deferens or obstruction of the epididymides may also have mutations in CFTR
. For males carrying CFTR
gene mutations, cystic fibrosis (CF) screening is indicated for their partners to better estimate the chance of having a child with CF.
This panel tests for the 39 most common CFTR mutations (listed
below), including the core panel of 23 mutations for cystic fibrosis as
recommended by the American College of Medical Genetics in 2004.
Chromosome analysis is by ISCN and ACMG guidelines with a minimum band resolution of 500-550. CFTR mutation detection and Y chromosome microdeletion detection are both qualitative molecular assays.