Discussion
In this study, we found that antioxidant treatments had a positive
effect on sperm parameters and that the two different molecule
combinations had similar effects. Male infertility may be the result of
some identifiable conditions (varicocele, cryptorchidism, hypogonadism,
and genetic abnormalities), but no cause can be identified in 30-40% of
infertile men. Such idiopathic infertility is characterized by decreased
spermatozoa, decreased sperm motility, and abnormal sperm morphology in
men that have no history of fertility-impairing disease and normal
findings in physical examination and laboratory tests (Cooper et al.,
2010).
It is assumed that various factors may be effective in idiopathic OAT,
including endocrine disorders, genetic abnormalities, and ROS (Jungwirth
et al., 2013). High ROS levels and oxidative stress have been associated
with sperm DNA damage, decreased sperm motility, and impaired
fertilization and embryo development (Agarwal et al., 2014). Since ROS
damages lipids, amino acids, carbohydrates, proteins, and DNA of
spermatozoa, this also affects sperm function (Agarwal et al., 2003).
Therefore, targeting OS is considered to be a strategy to increase
fertility and spermatozoa count and quality. Studies have shown that in
addition to vitamins (mainly A, B, C and E) and non-enzymatic
antioxidants including glutathione, metabolic coenzymes such as
pantothenic acid, CoQ10 and carnitines (l-carnitine and
acetyl-l-carnitine) and micronutrients (zinc, selenium, and copper) have
beneficial effects on fertility, especially sperm quality, and they are
therefore recommended as a potentially effective treatment for male
infertility (Walczak-Jedrzejowska, Wolski, & Slowikowska-Hilczer,
2013).
Several studies have reported that antioxidant therapy can reverse sperm
DNA damage and improve other sperm parameters (Majzoub et al., 2017) In
a meta-analysis, Omar et al. (2019) compared CoQ10 and L-carnitine with
a placebo and concluded that antioxidants could protect against free
radical damage in infertile men with higher ROS levels. Antioxidants
were also found to improve spermatogenic function and sperm DNA
integrity (Elumalai et al., 2009). Various clinical trials and systemic
studies including the use of various combinations of antioxidants
(L-carnitine, selenium, N-acetylcysteine, CoQ10, ubiquinol, vitamin E,
vitamin C, and lycopene) in infertile men reported the beneficial
effects of antioxidants on sperm concentration and motility and DNA
integrity (Agarwal et al.,2019 ). Abad et al. (2013) also conducted a
study to determine the effect of oral antioxidant therapy on the
dynamics of sperm DNA fragmentation in a cohort of 20 infertile patients
diagnosed with asthenoteratozoospermia. All subjects were given a
combination of 1,500 mg L-carnitine, 60 mg vitamin C, 20 mg CoQ10, 10 mg
vitamin E, 10 mg zinc, 200 microgram folic acid, 50 microgram selenium
and 1 microgram vitamin B12 for a period of three months. The results
showed that the rate of sperm with DNA damage was significantly reduced,
and there was a significant increase in the concentration, motility,
viability and morphology parameters of the semen analysis data.
Furthermore, a significant improvement in DNA integrity was observed at
all incubation points. The findings of that study were considered to
indicate that antioxidant therapy helped preserve sperm quality not only
in terms of important seminal parameters and basal DNA damage but also
DNA integrity. In another study, Gopinath et al. (2013) noted that the
administration of antioxidants in men with OAT resulted in a significant
improvement in their sperm count and total motility at 90 days compared
with the placebo.
Tremellen et al. (2007) conducted a prospective, randomized,
double-blind, placebo-controlled study in 60 couples with severe male
factor infertility. The participants were randomly assigned to take
either one capsule of a combination containing 6 mg lycopene, 400 IU
vitamin E, 100 mg vitamin C, 25 mg zinc, 26 microgram selenium, 5 mg
folate, and 1,000 mg of garlic or a placebo three months before their
partners’ in vitro fertilization or intracytoplasmic sperm injection
(IVF or ICSI) cycle. The antioxidant group showed a statistically
significant improvement in live pregnancy rates (38.5%) compared to the
control group (16%). A meta-analysis by Lafuente et al. (2013) showed
that treatment with CoQ10 resulted in a significant improvement in sperm
motility and density, but no significant improvement was observed in
live birth or pregnancy rates. In another study, combination therapy
with carnitine, CoQ10, vitamin E and vitamin C for three to six months
improved sperm concentration (Gvozdjáková et al., 2015).
In a systematic review published by Ross et al. in 2010, 17 randomized
studies were selected to evaluate the effects of oral antioxidants on
sperm quality and pregnancy rate in infertile men. The results showed
that the treatment of infertile men with oral antioxidants could reduce
seminal OS and improve sperm motility, but had a less predictable effect
on sperm concentration and morphology. In addition, oral antioxidant
therapy was associated with a significant improvement in spontaneous and
assisted pregnancy rates in six of 10 randomized studies included in the
analysis (Ross et al., 2010). In our study, the positive effects of two
different combinations on sperm parameters were determined. Since there
was no placebo group, it is not possible to comment on spontaneous
pregnancy rates; however, there was a significant increase on the
morphology values of both molecules.
Showell et al. (2011) evaluated whether supplementation with oral
antioxidants would improve the results of assisted reproductive
techniques when used in the male partners of couples undergoing assisted
reproductive techniques (ART), and how antioxidants might affect the
pregnancy rate, sperm parameters, and sperm DNA fragmentation. Data from
34 studies including a total of 2,876 couples were included in the
analysis. Antioxidant treatment was associated with a statistically
significant increase in the rates of live birth [odds ratio: 4.85,
95% confidence interval (CI): 1.92-12.24; p = 0.0008]and pregnancy
(OR: 4.18, 95% CI: 2.65-6.59; p<0.00001) compared to the
control groups (Showell et al., 2011). In a recent review, Clark et al.
(2013) examined 37 randomized controlled trials on complementary and
alternative medicine, including antioxidants and nutritional supplements
for the treatment of male infertility. Despite the presence of some
preliminary evidence of the efficacy of antioxidant interventions among
infertile patients, the authors emphasized the need for further research
before the adoption of these modalities in routine clinical use (Clark
et al. 2013). Similar conclusions were reached by Imamovic Kumalic et
al. (2017), who reviewed 32 studies conducted from 2000 to 2013 and
found that most confirmed the beneficial effect of antioxidants on at
least one semen parameters, with the most prominent effect being on
sperm motility, as well as the possible role of dietary supplements in
the treatment of idiopathic OAT.
In a study by Kızılay et al (2019)., infertile patients who underwent
varicocelectomy were given antioxidants together with surgical
treatment, and it was determined that the antioxidant + surgical
treatment group achieved statistically significant results in relation
to semen parameters and spontaneous pregnancy. In another recent study,
patients with high-grade varicoceles were randomized to surgical
treatment and L-carnitine supplementation groups, and favorable results
were obtained in all sperm parameters with motility increasing from 21.7
to 35.4% and 33.9 to 47.5%, respectively; normal sperm morphology from
46.3 to 60% and 56.6 to 69.7%, respectively, and seminal volume from
3.5 to 4.2 ml and 2.9 to 4.3 ml, respectively. The authors concluded
that additional therapy was as effective as varicocelectomy in improving
semen parameters, and could therefore be used as an alternative to
surgery (Sofimajidpour, Ghaderi, & Ganji, 2016). In a study by Busetto
et al. (2018) the effect of treatment on varicocele-induced infertility
was evaluated by applying an adjuvant antioxidant or placebo to 114
patients with and without varicoceles. A significant increase was found
in semen parameters and pregnancy rates of the group that had received
antioxidant supplementation for six months.
Many studies in the literature report positive results regarding
different agents and application methods and different doses of
antioxidant treatments. The groups given antioxidant treatments together
with ART, after varicocelectomy, or in patients with varicocele were
observed to have significant improvements compared to the untreated
groups. Due to the methodological and clinical heterogeneity of these
studies, it is difficult to make a comparison between the agents
administered or to make a definitive conclusion on the optimal dose and
duration for a given oral treatment. In our study, both antioxidant
combinations, which differ in terms of content, providing significant
results compared to the baseline values, shows that the use of this
treatment in infertile patients is useful. However, the two molecules
with different content screating similar effects raises further
questions concerning the molecules contained in each combination and
their dose.
The limitations of this study include the absence of a placebo group and
an evaluation of sperm DNA damage not being undertaken.