Frequency of Y chromosome microdeletions and chromosomal abnormalities in infertile Turkish men

Abstract

We have investigated the frequency and types of both major chromo-somal abnormalities by using standard cytogenetic methods and Y chromosome microdeletions by using gene based multiplex polymer-ase chain reaction (PCR) of infertile men with azoospermia and oli-gozoospermia to give appropriate genetic counselling before assisted reproduction techniques in Istanbul, Turkey. Cytogenetic studies were performed between February 2008-Decem-ber 2011 on 596 infertile men and screening of AZF deletions were performed by polimerase chain reaction on 332 infertile men, prior to ICSI treatment at Süleymaniye Education Research hospital, IVF Center, Istanbul. All the patients had primary infertility (severe oligozoospermia (<5 million/ml)-azoospermia) and non had obstructive azoopermia All patients underwent an andrological examination including medical history, presence or absence of anotomic anomalies (e.g varicosele, cryptoorchidism), testicular volume measurement. Sperm tests including , total sperm count, concentration, motility, morphology according to World health organization recommendations and blood measurements of relevant hormones were also performed. Cigarette and alcohol consumption behaviours of patients were registered and testing for human immunodefiency virus (HIV) was done. Informed consent was taken from all patients prior to collection of a heparinized blood sample. The mean age of the patients was 31.6 +/-6.2 years (range 20-53). The mean duration of infertility was 10.2 years (2-27). Sex chromosomal abnormalities were found in 61 subjects (61/596 = 10.23%). Their age range was 27-44 years. Third of these patients had 47,XXY karyotype (30/61 = 49.1%). Eight were translocations (7 /61=11.4 %) and three of them were Robertsonian translocations.

Full text

431
M. Dinçer et al., INFERTILE TURKISH MEN
GENETIC COUNSELING, Vol. 24, No 4, 2013, pp 431 - 434
LETTER TO THE EDITOR
FREQUENCY OF Y CHROMOSOME MICRODELETIONS
AND CHROMOSOMAL ABNORMALITIES IN INFERTILE
TURKISH MEN
BY M. DINÇER ¹, A .KARAHASANOGLU ², I. UZUN ÇILINGIR ², M. ERIÇ
OZDEMIR ², Z. OCAK ³, S. KARAHUSEYINOGLU ³ AND O. YUCEL ²
(1) Suleymaniye Education
and Research Hospital,
Department of Urology,
Istanbul, Turkey.
(2) Suleymaniye Education
and Research Hospital,
Department of Obstetrics and
Gynecology, Istanbul, Turkey.
(3) Suleymaniye Education
and Research Hospital,
Department of Embriology,
Istanbul, Turkey.
We have investigated the frequency and types of both major chromo-
somal abnormalities by using standard cytogenetic methods and Y
chromosome microdeletions by using gene based multiplex polymer-
ase chain reaction (PCR) of infertile men with azoospermia and oli-
gozoospermia to give appropriate genetic counselling before assisted
reproduction techniques in Istanbul, Turkey.
Cytogenetic studies were performed between February 2008- Decem-
ber 2011 on 596 infertile men and screening of AZF deletions were
performed by polimerase chain reaction on 332 infertile men, prior
to ICSI treatment at Süleymaniye Education Research hospital, IVF
Center, Istanbul.
All the patients had primary infertility (severe oligozoospermia (<5
million/ml) - azoospermia) and non had obstructive azoopermia
All patients underwent an andrological examination including medical
history, presence or absence of anotomic anomalies (e.g varicosele,
cryptoorchidism), testicular volume measurement. Sperm tests includ-
ing, total sperm count, concentration, motility, morphology according
to World health organization recommendations and blood measure-
ments of relevant hormones were also performed. Cigarette and alco-
hol consumption behaviours of patients were registered and testing for
human immunodeency virus (HIV) was done.
Informed consent was taken from all patients prior to collection of a
heparinized blood sample.
The mean age of the patients was 31.6 +/- 6.2 years (range 20-53). The
mean duration of infertility was 10.2 years (2-27).
Sex chromosomal abnormalities were found in 61 subjects (61/596
= 10.23%). Their age range was 27-44 years. Third of these patients
had 47,XXY karyotype (30/61 = 49.1%). Eight were translocations (7
/61=11.4 %) and three of them were Robertsonian translocations.

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GENETIC COUNSELING
18 (5.42%) of 332 patients were detected as having Y chromosome
microdeletions. The AZFc was the most frequently involved region in
the microdeletion process in the affected subjects. One of the affected
subjects had microdeletions in three regions (AZFa, AZFb, AZFc) and
two subject had in both AZFb and AZFc regions. All patients with
microdeletions were azoospermic.
Most authors have observed that chromosome abnormalities are far
more common among infertile men than in women with infertility (6,
12, 17). The reported range of chromosomal abnormality among in-
fertile men was found between 1.6%- 16.9% (5, 9). A study reported
from Turkey was found a frequency of 4.9% (1). In our study, the fre-
quency of chromosomal abnormality in infertile men was 10.23% and
30 (49.18%) of 61 patients was Klinefelter syndrome.
KS is the most common abnormality of sexual differentiation and oc-
curs in approximately 1 in 500 live births. Klinefelter syndrome is also
the most common form of male hypogonadism (11).
Another common chromosomal abnormality of infertile men is Rob-
ertsonian translocation. It was shown that Robertsonian translocation
was 10 times more frequent in patients attending infertility clinics than
in newborn population (2, 3). In our study, three patients had Rob-
ertsonian translocation. Prenatal diagnosis was recommended to these
couples.
Risk estimates of having an abnormal child and/or miscarriage vary
between 0 and 50% for fertile translocation carriers (13). In our sam-
ple, we found four translocation carriers. All affected patients were
told that the genetic risk for translocation carriers depends on the chro-
mosomes involved. Eleven autosomal inversions were found in our
patients. In pericentric inversions, each individual inversion carries its
own individual risk for unbalanced offspring and the risk for offspring
with unbalanced karyotypes is quite low for paracentic inversion het-
erozygotes (8, 15).
Studies from Turkey reported that the frequency of AZF deletions va-
ries between 1.3- 3.9% (13, 20). The frequency of patients with AZF
microdeletions in the present study was 5.42%. Our ratio is lower than
the ratios reported by other studies (1-55%) (4, 19).
The wide range of frequencies in different populations may be attribu-
ted to ethnic differences.
In our sample, the most frequently involved region was the AZFc regi-
on (61%). It was followed byAZFb (11.1%) and AZFb/AZFc (11.1%)
groups. These results are comparable with recent data (16).
A high frequency of Y microdeletions in the AZFa region has been
reported to occur in patients with Sertoli-cell only syndrome (10). In
our study, one patient with AZFa deletion was found to have Sertoli

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M. Dinçer et al., INFERTILE TURKISH MEN
cell-only syndrome. However, we did not detect microdeletions in the
AZFa region in the remaining twenty three men with SCOS.
Studies indicated that deletions on the long arm of the Y chromosome
involving a particular and consistent segment may lead to azoospermia
and sometimes to severe oligoospermia (14). AZF microdeletions are
the second most frequent genetic cause in the male infertility and the
type of the AZF deletions may affect the prognosis of TESE (7, 18).
In conclusion, the high occurrence (10.23%) of chromosomal abnor-
malities and Y chromosome microdeletions among infertile males
strongly suggests the need for routine genetic testing and counselling
prior to employment of assisted reproduction techniques.
Cytogenetic and molecular study should be performed to obtain relia-
ble genetic counselling in primary infertile man. Y chromosome dele-
tion screening is especially useful before the administration of assisted
reproductive techniques.
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ADRESS FOR CORRESPONDENCE:
Dr.Işil Uzun Çilingir
Yedikule Konakları B4/4
Yedikule/Istanbul
Turkey
Phone: +905325141526
E-Mail: isiluzu@gmail.com