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Approximately 20% of men seeking
help in fertility clinics have non-obstructive oligozoospermia or
azoospermia, 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 were previously 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 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 STSs found in the AZFa, AZFb,
AZFc and AZFd regions together with SRY and ZFY. Amplified products
are detected by fluorescent capillary electrophoresis.
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.
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.
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