Vol 44 # 4 December 2012 - Kma.org.kw

December 2012
stress, semen characteristics and clinical diagnosis in
investigated infertile patients. It is reported that the
total antioxidant levels in patients with idiopathic
infertility, varicocele, vasectomy reversal and infection
with varicocele were significantly less than those in
the fertile control group [26] . The association between
varicocele and infertility is well-known. Frequently,
men with varicocele have an abnormal spermiogram
that usually improves after repair [27,28] . ROS production
is usually high in those with a varicocele and improves
after varicocelectomy [26,29] . In addition, exposure to
cigarette smoke, a source of free radicals, contributes
to a deterioration of the spermiogram in patients with
a varicocele [30] . The total antioxidant capacity might
also contribute strongly to the pathophysiology of
male infertility, irrespective of the clinical diagnosis.
Many findings support that male infertility associated
with scrotal varicocele is at least in part related to
oxidative stress. Varicocele patients were detected to
have decreased antioxidant defenses both at the local
(seminal plasma) and systemic (blood plasma) levels [21] .
Barbieri et al measured the total antioxidant potential
defenses, not individually, of varicocele patients in both
seminal plasma and in systemic circulation. They report
that the antioxidant defenses decrease in both of them.
They conclude that varicocele-associated oxidative
stress is evident not only at the local site but also at the
systemic levels [21] . According to Ichioka et al, individual
susceptibility to varicocele-induced ROS may depend
on one or more of these genetic polymorphisms and
that the outcome of varicocelectomy may be influenced
by an individual’s genetic susceptibility to ROS [31] .
In our study, there was no statistically significant
difference for gene polymorphisms between study
and control group (Table 4), but it was significant in
patients with varicocele who had a vein diameter of
above 2.2 mm and forward progressive sperm motion
below 32% (Table 5). Increased ROS production can
deplete the defenses present in the testes and in
seminal plasma. For example, it has been reported
that total reactive antioxidant potential (TRAP) in the
internal spermatic vein (measured during surgery)
is significantly lower than in a peripheral vein [32] .
Varicocele reduces both the seminal and blood
plasma antioxidant defenses. In order to further
stress the relationship between local and systemic
defenses depletion, average values are plotted for the
different groups. One study shows that there is a good
correlation between both sets of values. This is the
first instance in which it is established that a systemic
decrease in antioxidant defenses is present in those
with a varicocele [33] . It is difficult to determine if the
systemic decrease is reflected in the seminal levels or
in systemic circulation [33,34] . Increased reactive oxygen
radicals in systematic circulation cause negative
effects on sperm function. This implies that significant
KUWAIT MEDICAL JOURNAL 320
antioxidant consumption at the testis level can be
related to the increased ROS production [21] . The results
discussed above suggest that antioxidant defenses
could be depleted both locally and systemically in
varicocele patients. In particular, it was considered
important to establish if oxidative stress indicators
are modified and non-enzymatic antioxidants are
depleted in seminal and blood plasma of varicocele
patients [32] . In our study, we used peripheral blood
both in the study group (infertile patients) and the
control group (fertile group), because using the
specimen from the varicose vein of the control group
was an ethical concern. We determined statistically
significant rate of gene polymorphism in enzymatic
antioxidant defence systems in patients with clinical
varicocele, with a diameter of spermatic vein above 2.2
mm and forward progressive sperm motion below 32%.
But, we could not determine any significant difference
in terms of gene polymorphisms in our infertile study
group compared to fertile control group. There was
also no statistically significant difference in patients
with total sperm motion (below and above 40%). This
is a controlled prospective study and it is also the
first study which searches the association between
infertility and gene polymorphism of enzymatic
antioxidant defense system. Although our patient and
control group is small, this is the first pilot study which
includes patients with fertility and infertility, their
sperm features (progressive and total sperm motion)
and spermatic vein diameter (with and without
varicocele) in literature. We want to continue the study
with larger groups in future. Perhaps then, we will
also find a relationship between infertility and gene
polymorphism as the number of the patients increase.
CONCLUSION
Antioxidant gene polymorphisms can be detected
in fertile and infertile men with varicocele. It would be
important to investigate whether these polymorphisms
can take place in fertile and / or infertile men with
varicocele. These polymorphisms might represent
a risk factor for Turkish men with clinical varicocele
and forward progressive sperm motion. This is a pilot
study. We intend to continue these studies with a larger
sample size to confirm these findings.
Declaration: The authors had no conflict of interest.
REFERENCES
1. Jarow JP, Coburn M, Sigman M. Incidence of varicoceles
in men with primary and secondary infertility. Urology
1996; 47:73.
2. Safarinejad MR, Shafiei N, Safarinejad S. The role of
endothelial nitric oxide synthase (eNOS) T-786C, G894T,
and 4a/b gene polymorphisms in the risk of idiopathic
male infertility. Mol Reprod Dev 2010; 77:720-727.