Y-Chromosome Microdeletions
Approximately 20% of men seeking help in fertility clinics have non-obstructive oligozoospermia (low sperm count) or azoospermia (absence of sperm), a high percentage of which are positive to Y-chromosome microdeletions (YCMD). The azoospermia (AZF) region on the long arm of the Y-chromosome (Yq) is known to control spermatogenesis. Another region at the distal end of the q-arm contains the DAZ gene that is deleted in azoospermia.
Both small and large deletions on the Y-chromosome have been associated with infertility in males. A number of sequence tagged sites (STS) spread across the Y-chromosome are used to detect any deletions that might be present.
Importance of Test
The test is useful to males diagnosed with oligozoospermia, azoospermia, idiopathic infertility and those undergoing testicular sperm extraction (TESE) or prior to ICSI. Testing for microdeletions is not necessary for men with obstructive azoospermia where ICSI (Intracytoplasmic Sperm Injection) is used, because spermatogenesis should be normal in these individuals. Y-chromosome microdeletions are identified in 6 - 18% of men with non-obstructive azoo- or oligospermia.
Test Methodology
DNA is extracted from peripheral blood or fresh sperm. Multiplex PCR is performed to amplify 8 Y-chromosome STRs found in the AZFa, AZFb, AZFc and AZFd regions together with SRY and ZFY. Amplified products are detected by fluorescent capillary electrophoresis.
Clinical Significance
AZF has been divided into four regions known as AZFa, AZFb, AZFc and AZFd. These regions are of prognostic importance for the success of ICSI.
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Deletions of AZFa are rare but can be associated with a very severe phenotype and complete absence of spermatogenesis.
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AZFb deletions are associated with zero probability of finding mature spermatozoa due to developmental arrest of germ cells.
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AZFc deletions are the most frequent deleted region and include the DAZ gene. Partial deletions are associated with a 50% success of TESE while in oligozoospermic males sperm counts can drop with time and so cryopreservation can be adviced.
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AZFd deletions are associated with mild oligozoospermia and even normospermia with over 90% abnormal morphology.
YCMD test results will determine whether to continue with intruterine insemination or advancing ICSI. YCMD is important to determine the cause of spermatogenic failure and gives information for appropriate clinical management of infertile males and their future offspring. Any male child inheriting a Y deleted sperm is at risk of infertility. Females are not affected. YCMD is not the only cause of infertility, as other genes might be responsible for the condition and so a negative test does not exclude possible infertility.
Sample Requirements
Peripheral whole blood collected by venipuncture in an EDTA container. Please send the sample at ambient temperature. Serum or Plasma samples are NOT useful for this test.
Sperm stored at 4°C is also useful for this test. Please send fresh sperm samples of less than one week old.
