Male infertility: What do we earn
by microdeletion : It implies a defect in
deletion of one segment of Q arm of Y which is responsible for sperm
production. This is not uncommon genetic
defect ie. Y chromosome microdeletion: The
importance of Y chromosome microdeletion screening and genetic counseling is
strongly emphasized for infertile men prior to employment of assisted
reproduction techniques.
Q. Where is the defect?? Deletion of one particular segment of Y chromosome i.e., long arm of the Y chromosome (Yq11) is considered the most
common genetic cause of male infertility . The
portion of Y chromosome which regulates sperm production is called AZF(Azoospermic
Factor) segment / portion of Y chromosome .
Prevalence in azoospermic men?? Ans . Out of all azoospermic men & OAT as many as
28% had sex chromosomal, abnormalities. As
many as 14% of NOA and 20% of Oligozoospermia men had such Y
microdeletions in particular segment .The portion of Y chromosome which
regulates sperm production is called AZF(Azoospermic Factor) segment / portion
of Y chromosome .It contains several genes which are again located in different
loci in that segment . The most frequent
microdeletions were detected in the AZFc region, followed by AZFbc, AZFb, AZFa, AZF abs(Yq),
Yp(SRY)+Yq, and
partial AZF c regions.
Lets view briefly how prevalent is Y Chromosome
Microdeletions in Infertile ?? Men with
Non-obstructive Azoospermia and Severe Oligozoospermia. Y chromosome microdeletion is a major genetic cause of azoospermia.
What about serum levels of reproductive hormones?? Levels of FSH
and LH in patients with AZFc
microdeletion were significantly lower, but in other forms of deletion
disorders the reproductive hormones are normal range. Hormone analysis:
Peripheral
blood was collected in a vacutainer serum separator tube (Becton Dickinson,
USA). Levels of serum follicle-stimulating hormone (FSH), luteinizing hormone
(LH), testosterone (T), prolactin (PRL), and estradiol (E2) were
measured using chemiluminescence immunoassay and radioimmunoassay. Normal male
reference ranges were FSH, 1.5–12.4 mIU/ml; LH, 1.7–8.6 mIU/ml;
T, 2.41–8.27 ng/ml, PRL, 4.04–15.2 ng/ml, and E2,
7.4–42.6 pg/ml.
Clinical Relevance?? There is a need for Y chromosome microdeletion
screening prior to ICSI or any there ART (where there is Azoospermia or severe
OAT) for correct diagnosis of male
infertility. Obtaining reliable genetic information for assisted reproductive
techniques can prevent unnecessary treatment and vertical transmission of genetic defects to offspring.
: Microdeletion : How relevant to
us?? It will be prudent to do for genetic test ( Micro
deletion of a particular segment in Y chromosome ) of those male partner who are being selected for ICSI
due to a) azoospermia or b) NOA i.e. nonobstructive azoospermia. Detection of Y chromosome microdeletions is of great use
for guiding clinical diagnosis, helping selecting treatment schemes, and
reducing the incidence of genetic diseases. In the following
Many research
works were carried out by andrologist to investigate the frequencies and types
of Y chromosome microdeletions in infertile men and to analyze the relationship
between the levels of reproductive hormones and Y microdeletions. The most
commonly cited study summary is as
follows:-
A
total of 1,226 infertile men were screened for A) Y chromosome microdeletions using multiplex PCR assay..Further, B) Karyotype analysis was also performed on peripheral blood lymphocytes
with standard
G-banding. C) Serum reproductive hormone
levels were measured.
Out of 1226 such men as many as 11% had Y microdeletions.
To put in other way round, as many as 14% of NOA and 20% of Oligozoospermia
men had such Y microdeletions in particular segment .The portion of Y
chromosome which regulates sperm production is called AZF(Azoospermic Factor)
segment / portion of Y chromosome ,It contains several genes which are again
located in different loci in that segment
. The most frequent microdeletions were detected in the AZFc region, followed by AZFbc, AZFb, AZFa, AZF abs(Yq), Yp(SRY)+Yq, and partial
AZF c regions.
Levels of FSH and LH in patients with AZFc microdeletion were
significantly lower, Out of all
azoospermic men & OAT as many as 28% had sex chromosomal, abnormalities.
There is a need for Y chromosome microdeletion screening prior to ICSI or any
there ART (where there is Azoospermia or severe OAT) for correct diagnosis of male infertility.
Obtaining reliable genetic information for assisted reproductive techniques can
prevent unnecessary treatment and vertical transmission of genetic defects to
offspring. Microdeletion of the azoospermia factor (AZF) region: It is a genetic diseases Microdeletions of
the azoospermia factor
(AZF) region located on the
long arm of the Y chromosome (Yq11) is considered the most common genetic cause of male infertility .
The AZF region is divided into three nonoverlapping
subregions called AZFa, AZFb, and AZFc, all of which are required for normal
spermatogenesis.
Y Chromosome
Microdeletions in Infertile Men with Non-obstructive Azoospermia and Severe
Oligozoospermia is an important issue to geneticists prior to ART in case of
azoospermia as important as is with Cong
Vas Obstruction (cystic fibrosis).
Questions to the members: Please
reply and those who will answer by 2 hours will
be rewarded by a large Post new
Yr Cake. “Should we investigate for Y microdeletion, obviously in male partner
in cases of RPL (Rec Preg Losses)?
Of all the possible microdeletion AZFc
deletion is the most frequent. Several previous studies have reported a range
(2%–16%) of chromosomal
abnormalities in infertile patients. Amongst the men who exhibited Y
chromosomal abnormalities (other than microdeletion) , or nonchromosoanl azoospermia or OAT what is
the frequency of Y chromosome microdeletions in such 3 types of cases ??
Ans: This may be as high as 25-30%. Besides
large deletions, including those in the AZFbc,
AZFabc(Yq), and Yp(SRY)+ Yq regions, can cause chromosomal instability
there can be for chromosomal
rearrangements or Y chromosome
loss. The frequency of chromosomal abnormalities may be as high, as 60-70% AZFbc & 100% in the
AZFabc(Yq). As such
AZFabc(Yq) disorders are worst so far as impairment of spermatogenesis
is concerned. There are other loci
disorders too. Like Yp(SRY)+Yq regions.
Moreover, all of these abnormalities involved the sex chromosome, with a
majority of 46,X,idic(Y),
46,X,idic(Y)/45,X, 46,XX, or 46,X,del(Y) abnormalities. An association
between Y chromosome microdeletions and an isodicentric Y chromosome or
46,X,idic(Y)/45,X chromosomal mosaicism has been proposed previously .
Many
genetic studies in male infertility with Azoospermia or severe oligozoospermia
have suggested that genes in the AZF region are not only associated with
spermatogenesis, but also with the stability and viability of the Y chromosome,
such that microdeletions are an
intrinsic element of AZF gene polymorphisms that can lead to translocations and
deletions, together with gain or loss of Y chromosomes.
Levels of FSH and LH in infertile patients with Yp(SRY)+Yq deletions were significantly higher, whereas those in patients with
AZFc deletion were significantly lower than those in infertile patient without
Y microdeletions. The level of T in patients with AZFabc(Yq) or Yp(SRY)+Yq
deletions was significantly lower than that in patients without microdeletions.
However, there were no significant differences in the levels of FSH, LH, T,
PRL, or E2 between total patients with and without Y
microdeletions..
Please do suspect microdeletion of Y
Chromosome if serum Testosterone is too
low. Ans:/Logic :-The levels of FSH and T in patients with Y
microdeletions were significantly lower than that in patients without Y
microdeletions, whereas the level of LH was significantly higher in an Indian
study .
Changes
in the gonadal morphology in microdeletion cases ? Ans -Surveys have
also shown changes in male hormone physiology according to levels of FSH, LH,
and T as well as modification of gonadal morphology in individuals affected by
microdeletions of the Y chromosome. Further research is necessary to determine
the nature of the correlation between Y microdeletions in infertile patients
and levels of these reproductive hormones.
Why microdeletion has become
relevant ?? Ans:-More and more infertile men
are choosing assisted reproduction techniques, such as TESE and ICSI, to have
offspring. With the help of assisted reproduction techniques, it is possible
for patients with severe impaired spermatogenesis to father children. However,
these technologies can increase the risk of
transmitting genetic disorders. Thus, before undergoing assisted
reproduction, an understanding of the genetic defects responsible for
infertility is essential to avoid unnecessary treatments and vertical transmission of these
abnormalities to the offspring. This
has been worked out for different loci deletion , For instance abnormal gene vertical transmissions by ICSI
may be as high as follows : In AZFbc
(20.90%), AZFb (8.21%), AZFa (7.46%), AZFabc(Yq) (5.22%), Yp(SRY)+Yq (3.73%),
and partial AZFc (2.99%) deletions. AZFc microdeletion can yield 56.55%
vertical transmissions as compared to
deletions in AZFa, 7.74%, AZFb, 5.95%, AZFbc, 22.02%, and AZFabc, 7.74% . However, Yp(SRY)+Yq and partial AZFc
deletions were not found in their azoospermic and severely oligozoospermic
patients .
What is the most common type of Y microdeletion ?? Ans:-The AZFc deletion was the most common pattern of
AZF microdeletions in patients with non-obstructive azoospermia and severe
oligozoospermia and Several candidate
fertility genes have been discovered within the AZFc region. It is still not clear why AZFc
deletion is so frequent, but it could be caused by repetitive sequences in this
region. It has been suggested that men with AZFc deletion are capable of
producing sperm, but some patients do not have any sperm inside their
seminiferous tubules .Studies have shown that men
with AZFc
deletion have shown a good prognosis for successful retrieval of sperm by TESE,
whereas patients with deletions in
the AZFa and AZFb regions have not .
What happens in NOA?? What kind of
microdeletion??
Ans:--AZFa, AZFb, AZFbc, AZFabc(Yq), and Yp(SRY)+Yq deletions were found only in non-obstructive azoospermic
males. Partial AZFc deletion in following loci have been observed. Such
loci in long arm of Y chromosome are
(sY157/s Y158 or sY254/sY255) was found in three non-obstructive
azoospermic patients and one severe oligozoospermic patient in our study.
Previous study has suggested a link between a partial deletion in the AZFc
region and spermatogenic failure. But opinion amongst andrologist & geneticist vary and no final consensus have
been arrived as yet, But fact remains
that before ICSI in cases of severe
OAT
& Azoo there is a need for study of
AZF deletion to avoid vertical transmission in male offspring or . at least the
prospective parents may be for warned about such possibility ,It is like CABV
in cystic fibrosis gene mutation ,Regarding relevance of evaluation of Y
deletion(micro) the consensus is still cloudy but as senior practioner if there
is OAT and spent preg or preg with some male antioxidants then icy will be fair
to tets for microdeletion and kind of
deletion as few deletions are notoriously will lead to Rec Failure(RPL), In
such cases AID /Adoptions are the preferred option but decision lies better kef
to concerned couple, However, other
researchers have disagreed, proposing that this is simply a polymorphic
deletion with no clinical ramifications .
.
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