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International Journal of Reproductive BioMedicine
Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences of Yazd
ISSN: 1680-6433 EISSN: 2008-2177
Vol. 3, Num. 1, 2005, pp. 25-29
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Iranian Journal of Reproductive Medicine Vol.3. No.1, 2005,
pp: 25-29
The effect of oral administration of Pentoxifylline on sperm
motility of asthenozoospermic ejaculates from men with or without testicular
varicoceles
Mohammad Reza Moein,1M.D., Mohammad Ali Khalili,2
Ph.D., Arash Davoudi,3M.D.
1 Assistant Professor, Research & Clinical Center for Infertility, Yazd University of Medical Sciences, Yazd, Iran.
2 Associate Professor, Fertility & Infertility Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
3 Research & Clinical
Center for Infertility, Yazd University of Medical Sciences, Yazd, Iran.
Corresponding Author: Dr Mohammad Ali Khalili, Fertility & Infertility
Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Email: khalili59@hotmail.com
Code Number: rm05005
Abstract
Background: Pentoxifylline
(PX) is a methyxanthin derivative that influences the sperm motion
characteristics. In general, PX has been reportedly effective in preserving
sperm motility in vitro, also when administered orally to the asthenozoospermic
patients.
Objective: The main
objective of this prospective clinical trial study was to rule out the effect
of oral administration of PX on sperm progressive motility of asthenozoospermic
ejaculates obtained from men with or without mild testicular varicoceles. In
addition, the role of patient’s age on sperm motility following PX administration
was investigated.
Materials and Methods: A
total of 68 infertile men with asthenozoospermia were allocated to this study.
Following physical examination, 20 cases were found with mild varicocele of
testis. A dosage of 400 mg PX/ twice daily for duration of 3 months was
administered to each patient. Two semen samples (one before and one after the
PX therapy) were evaluated under blind condition. Semen parameters of sperm
concentration, total and fast progressive motility (%) and morphology (%) were
analyzed for each sample. Also, the sperm motion characteristics of
asthenozoospermic patients with testicular varicocele were compared with cases
lacking varicocele. The subjects were divided into two age groups of <30 and
≥30 years old.
Results: PX was
significantly effective on the fast progressive motility of sperm (p<0.01).
Also, total progressive motility was enhanced from 26.82±16.8 to 29.60±22.2
with PX therapy. However, PX did not have any negative effect on other semen
parameters. Oral therapy of PX was also effective in improving the fast
progressive motility of sperm of samples from cases with or without mild
testicular varicocele (p<0.01). Fast progressive motility was also significantly
enhanced in ejaculates of men from both age groups.
Conclusion: Our
results demonstrate that low dose of oral therapy of PX is significantly useful
in enhancing fast progressive motility of sperms from infertile men with
asthenozoospermia. Also, testicular varicocele did not interfere with enhancing
effect of PX on sperm motility.
Key
words: Sperm Motility, Pentoxifylline, Varicocele, Asthenozoospermia.
Introduction
PX is a methyxanthin derivative in the same pharmacologic group
as caffeine that inhibits the breakdown of cyclin adenosine monophosphate (cAMP).
This
generates cellular glycolysis and endogenous adenosine triphosphate (ATP)
production that influences the sperm motion characteristics (1, 2). In general,
PX has
been reportedly effective in preserving sperm motility in vitro, also when administered
orally to
the asthenozoospermic patients (3-6).
One of the major causes of male factor infertility is related to
asthenozoospermia, particularly severe cases, which may influence the pregnancy
success rates following assisted reproductive techniques (ART) (7). Therefore,
a potential pitfall exists for these infertile men where their only infertility
problem resides in sperm motility parameters. Thus, improvement of sperm
motility with application of PX may not only be beneficial for intracytoplasmic
sperm injection (ICSI) programs, but in some cases, it may also substitute
treatment protocols for a more natural treatments, such as in vitro
fertilization (IVF), or even intra-uterine insemination (IUI) cycles (3).
In our previous experimental as well as clinical studies, the role of in vitro
application of PX on motility of spermatozoa retrieved from different sources
of ejaculate, epididymis, and testis were investigated (3, 8). The results
demonstrated that PX was successful in enhancing both non-progressive as well
as progressive sperm motility. In addition, 60% of microsurgically retrieved
samples with total sperm immotility showed motion ability following PX
application. Therefore, the main objectives of this prospective study was to
evaluate the role of oral administration of PX on sperm progressive motility
from asthenozoospermic samples obtained from patients of different age groups.
Also the effect of PX on sperm motility of asthenozoospermia from cases with
or
without mild varicocele of testis was investigated in a controlled setting.
According to our knowledge, the later objective of this study has not been
reported by other investigators yet.
Materials and Methods
Patients
A total of 68 infertile men with asthenozoospermia were allocated to
this prospective clinical trial study. Following physical examination by
urologist, 20 of them were found with mild varicocele of testis. The
individuals were divided into 2 age groups of <30 and ≥30 years old.
All the ejaculates were evaluated under blind conditions at our andrology
laboratory. Every patient was assigned to collect two semen samples: one right
before oral administration of PX (control) and one three months after PX oral
therapy (PX). Asthenozoospermia was defined according to the WHO guideline as
samples with <50% progressive sperm motility (9).
Ejaculate Samples
Fresh ejaculates were collected by masturbation in sterile containers.
Following liquefaction, semen analysis was performed according to WHO
guidelines (9). The semen parameters of concentration and 2 types of
progressive motility (fast, fast + slow) were evaluated using Makler Chamber
and light microscopy. Geimsa (Merck Co., Germany) staining and oil immersion
were used for evaluating round cells and percentage of normal sperm morphology.
Oral Administration of Pentoxifylline
All patients were administered low dosage of 400mg PX (Apotex Inc., Canada) twice daily for 3 months. For each patient, semen parameters were measured right before
and after the PX treatment period.
Statistical Analysis
The statistical analysis was performed using SPSS software for windows.
Paired-t test and non-parametric test (two related sample Wilcoxon test) were
applied for the comparison of sperm motility between control (before PX
therapy) and PX (after PX therapy) samples. Results are expressed as mean ±SD. p
value of <0.05 was considered as significant.
Results
The mean age of the patients was 39.3±7.7 years old (range: 20-58). Table I
presents the results of semen parameters from asthenozoospermic men. The
percentage of fast progressive motility of sperms was significantly enhanced by
PX (p<0.01). Although, progressive motility of spermatozoa was improved
following PX application, but this was insignificant (29.60% versus 26.82%).
The rates of fast as well as progressive motility of spermatozoa from patients
with or without varicocele of testis are presented in Table II. The results
showed that significant fast progressive motility was observed in both groups
of patients with or without varicocele. Table III represents the correlation
between different age groups with rate of sperm progressive motility. In
general, patients younger than 30 years were presented with higher rate of
sperm
motility than older
men before application of PX. Following PX therapy, fast motility of
spermatozoa from both age groups enhance significantly (p<0.05).
Table I.Semen
parameters of 68 asthenozoospermic samples from infertile men.
Variable
|
Control
|
PX
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Sperm count (x106)
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44.6±7.6
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40.1±10.3n
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Round cell (x106)
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2.5±0.8
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2.7±1.4n
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Normal morphology (%)
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32.92±14.4
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32.89±19.0n
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Progressive motility (%)
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26.82±16.1
|
29.60±20.2n
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Fast motility (%)
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6.14±5.7
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9.62±10.6*
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n: non-significant,
*: p<0.01 compared with control samples
Values
represent the mean ± SD
Table II. The rate of sperm motility
of asthenozoospermic samples from men with or without varicocele.
|
Varicocele (n=20)
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No varicocele (n=48)
|
Type of motility
|
Control
|
PX
|
Control
|
PX
|
Progressive (%)
|
27.75±15.8
|
31.40±22.4n
|
25.02±17.3
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28.43±22.3n
|
Fast (%)
|
5.62±6.4
|
11.06±12.4*
|
6.40±5.5
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8.90±9.8*
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n: non-significant,
*p<0.05 compared with control samples
Table III. The correlation between patient’s age and the rate of sperm
motility in asthenozoospermic samples.
|
Age<30 (n=38)
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Age≥30 (n=30)
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Type of motility
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Control
|
PX
|
Control
|
PX
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Progressive (%)
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30.55±15.8
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34.75±22.0n
|
20.50±16.9
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23.81±21.3n
|
Fast (%)
|
7.03±6.4
|
10.32±10.6*
|
4.52±5.8
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8.35±10.9*
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n: non-significant,
*p<0.05 compared with control samples
Discussion
In our previous study on the effect of in vitro application
of PX on motility of spermatozoa from asthenozoospermic samples, progressive
motility
was
significantly increased from 26.5% to 44.8% (p<0.001) (3). This is not in
agreement
with our current study, where progressive motility was slightly increased
following oral administration of PX. However, the results showed that
significant improvement of fast progressive motility was achieved after PX oral
therapy. Therefore, it seems that PX is more effective in stimulating sperm
motility when applied in vitro to the culture media. In a study done by Shen et
al. (1991), in vitro and in vivo effect of PX on sperm motility was
measured for the treatment of male infertility (10). In vitro application of
PX increased the motility of ejaculated sperm of asthenozoospermic patients.
Also,
oral application of PX for three months significantly enhanced the progressive
motility, with no effect on concentration of spermatozoa. They concluded that
PX may be used either in vitro or in vivo for improving asthenozoospermia. In
another study, 15 young men with asthenozoospermia were admitted for oral
therapy of 1200 mg/day PX (high dosage) for over four months (11). The results
showed a significant improvement of progressive motility. It is important to
note that five patients achieved a normalization of their semen quality.
Therefore, it seems that PX is a beneficial alternative for treatment
of men with asthenozoospermia. In addition, 65 infertile men with either
asthenozoospermia or oligozoospermia were treated with oral PX for three
months. In asthenozoospermia group, a significant increase of progressive
motility of sperm was noted which concurrently improved the conception rate.
However, the semen parameters in oligozoospermic men were not affected. It was
proposed that PX treatment improves the microcirculation within the
epididymis as well as male accessory sex glands. This may lead to an improved
sperm maturation / motility (12). In the present study, we noticed that PX was
a safe drug with no deteriorating effect on semen parameters of concentration
or sperm morphology. This is important in clinical settings, because while the
quality of motility is improved with a useful drug- PX, other parameters such
as sperm concentration, should not be negatively affected.
In one study, 1200mg/day of PX was administered orally to twenty-five patients
with asthenozoospermia, sperm motility was enhanced from 25.5% to 35.5% and 42%
after three and six months of treatment, respectively. Control semen samples
showed some, but insignificant, change in sperm motility with PX. Also, no
statistical changes were found in other semen parameters. The results suggested
that PX is useful treatment in cases of male infertility with asthenozoospermia
(4). Furthermore, role of oral administered PX on motility and density of
sperms, as well as fertilization rate were investigated by Faka et al.
in 1994 (13). In contrast to our results, their study showed that PX did not
improve the motility, density, or fertilization rate. However, they only
investigated their work on 14 patients with poor semen parameters. It is,
therefore, possible that if they would study on a larger series of cases with
only asthenozoospermia, a different outcome would be achieved.
Another finding generated from this investigation was the effect of oral PX
on sperm fast motility obtained from men with or without mild testicular
varicoceles. In humans, varicoceles have a variable influence on testicular
function, leaving it unaltered in some cases, but causing spermatogenic arrest
in others (14). Also, it may result in impairment of sperm production and
abnormal semen quality ranging from oligospermia to azoospermia (15). Our findings
showed that a comparable motility characteristic was observed in cases with or
without varicoceles. However, the oral therapy of PX improved the fast sperm
motility
in both groups of men (p<0.05). This may indicate that presence or absence
of varicoceles is not involved with the enhancing effect of PX on motility.
Pasqualotto et al. (2005) also found that sperm motility was lower in
patients with varicocele (37.2%) than cases without varicocele (58.9%) (16).
The difference was, of course, significant. In contrast, our results showed
that the rate of sperm progressive motility in patients with varicoceles, and
those lacking varicoceles were similar.
The other goal of the present study was to rule out the association of male
age and sperm motility. The results confirmed that men under the age of 30
had
higher rate of progressive motility of sperms, when compared with older men.
However, the stimulating effects of PX on sperm motility of both age groups
were similar. This shows that, although in natural condition the age is directly
associated with quality of sperm motility, but PX is not. A recent study by
Eskenazi et al. (2003), on 97 non-smoking men aged from 22 to 80 years
showed that sperm progressive motility decreased by 3.1% per year. It was shown
that sperm motility decreased continuously between 22-80 years of age, with no
evidence of a threshold (17). However, Kumtepe and associates (2003) did not
observe any differences in sperm parameters in 2 groups of patients <40
(n=692) or >40 (188) years old (18). There is still controversy whether
advanced male age is associated with poor sperm quality or not. In our study,
we divided the infertile men into two age groups of <30 and ≥30 years
old. There were two reasons to define 30 years for dividing the study
population into the aforementioned age groups. First, the number of cases were
comparable in two groups of <30 and ≥30 years (38 vs. 30). Secondly,
the number of men beyond 40 was very limited in our patients under study.
Therefore, to draw a conclusion on the sperm motility in relation to male age,
we noticed that advancing age is directly related with poor sperm progressive
motility. However, PX was significantly effective in improving sperm fast
motility in different age groups.
Conclusion
In conclusion, our results showed that PX is a useful drug for treating the
sperm motion characteristics of patients with asthenozoospermic ejaculates.
Also, asthenozoospermic patients with mild varicocele of testis may benefit
from the oral therapy of PX. Finally, regardless of the male age, the results
showed that significant improvement was observed on sperm fast motility.
Whether PX should be applied in vitro or in vivo to enhance sperm motility
needs further investigation.
Acknowledgments
The authors wish to thank the clinical and laboratory staff of Research and
Clinical Center for Infertility for their kind assistance in this prospective
clinical study. Also, authors would like to appreciate Dr. Ashok Agarwal, the
director
of Center for Advanced Research in Human Reproduction, Infertility, and Sexual
Function in Cleveland, Ohio for his kind suggestions during the preparation of
this manuscript.
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