Karyotyping is the gold standard when a genetic cause for infertility is suspected.
When is the test recommended:
In patients with fertility issues:
In patients with developmental disorders:
DNA analysis for Y-chromosome microdeletion
This test is recommended for men with non-obstructive azoospermia (NOA) and severe oligoasthenoteratozoospermia, regardless of the presence of other testicular pathologies. The analysis is indicated in men with sperm concentrations below 10 mln/mL.
Microdeletions (submicroscopic loss of genetic material) in the long arm of the Y chromosome are a common cause of male infertility. They are specifically related to impairments of spermatogenesis. Microdeletions of particular interest are those in the AZF-regions (azoospermia factor regions), which include genes of crucial importance to the development and maturation of spermatozoa.
When is the test indicated?
DNA analysis for Y-chromosome microdeletions is recommended in cases of severe semen analysis abnormalities – microdeletions are found in 10–15% of men with azoospermia (absence of sperm in the ejaculate) when it is not caused by obstructive defects of the seminal ducts and in 5–10% of men with severe oligozoospermia.
The Y-chromosome microdeletion test has additional value when assisted reproduction techniques are used:
A venous blood sample is needed for DNA analysis for Y-chromosome microdeletions, preferably not fasting. Results are ready within 1–2 weeks
DNA analysis for CFTR gene mutations
CFTR gene mutations screening is highly recommended in infertile men with unilateral or bilateral congenital absence of the sperm ducts. If a CFTR mutation is confirmed in one of the partners, a DNA analysis of the other must be done to assess the risk of passing cystic fibrosis to the offspring.
FMR1 gene analysis
Carrier testing for fragile X syndrome is strongly recommended in women with oligomenorrhoea due to primary ovarian disfunction (incl. premature ovarian failure). Another indication is poor response to ovarian stimulation. If a premutation is confirmed, genetic counselling is recommended, as there is a risk for the birth of boys with intellectual impairment. In such cases, preimplantation genetic testing can be recommended to rule out fragile-X syndrome.
DNA analysis for hereditary thrombophilias
The test is recommended for women who have a medical history of stroke, infarction, pulmonary thromboembolism, venous thrombosis, second-trimester miscarriage(s), stillbirth, or a first-degree family member (sibling or parent) who has such history or a confirmed clinically significant genetic thrombophilia.
Thrombophilias lead to an increased tendency for blood clotting. They can be caused by genetic and non-genetic factors (for example, immunological aberrations). About 40% of venous and arterial thrombosis cases are hereditary, yet, overall, thrombophilias are complex multi-factorial diseases and not the result of a single genetic abnormality.
The genetic variants most often screened in women with infertility are FV (Factor V Leiden mutation 1691G>A), FII (Factor II prothrombin – mutation G20210A), PAI-1 (Plasminogen activator inhibitor 1 – 5G/4G variant), MTHFR (Methylenetetrahydrofolate reductase – 677C>T and 1298A>C variants). Those variants are routinely screened in Nadezhda Hospital’s genetic lab.
The test is performed on venous blood samples, preferably drawn 30 to 60 minutes after eating. Results are available in one to two weeks.