THE ROLE OF

GLUTATHIONE IN
MALE
INFERTILITY

Dr. Mohanned Hussam Mohammed Saeed

Alkumait

F.I.B.M.S (Urology)
2018

​
The Role of Glutathione in Male Infertility
​2

Abstract
Background
Male infertility proves to be a psychological distress for the married couples. Numerous
research studies have attempted to determine the causes of male infertility with the
objective of developing therapeutic approaches to effectively improve various semen
parameters. The presented intervention is a quantitative approach that categorically assesses
the therapeutic advantage of oral GSH (glutathione) administration on various semen
parameters including sperm concentration, morphology, and motility in infertile males. The
study hypothesis presumes the positive/linear correlation of the selected sperm parameters
with orally administered glutathione.
Materials and Methods
The prospective placebo-controlled study 101 infertile adult males through random
selection between the timeframe of Jan 2017 to Mar 2018. The selected subjects did not
experience any chronic disease of the reproductive system and exhibited normal female
factor. GSH oral therapy was administered between 0 to 6 months timeframe.
Results
The findings recorded at 0 weeks, 3 months, and 6 months interval revealed a significant p-
value (between 0.01 to 0.03 for sperm motility, morphology, and concentration.
Outcomes
The study findings revealed a strong positive relationship between oral glutathione therapy
and the selected sperm parameters.
 Key Terms: Oral GSH, male infertility, glutathione, sperm concentration, sperm
morphology ,sperm motility. ​

Introduction
Male infertility is associated with the psychological trauma of the married couples
and poses a serious threat to their mental health and wellness to a considerable extent.
Oxidative stress is one of the major causes of male infertility and substantially impacts the
equilibrium between protective antioxidants and ROS (reactive oxygen species). Oxidative
stress not only impacts the male reproductive lifespan but also affects the cellular function
and aging process. Several antioxidants antagonize the adverse impact of reactive oxygen
species while facilitating the cellular repair processes. These antioxidants exhibit
scavenging action of free radicals and substantially minimize their abnormal levels in the
male body. Glutathione (GSH) effectively antagonizes the level of reactive oxygen species
while effectively inducing the antioxidant defense mechanisms of the human body (Adeoye
et al. 2018).
Antioxidant property of GSH helps in controlling the level of free radicals in the
context of stabilizing reproductive microenvironment. Glutathione in this manner is
believed to improve the reproductive capacity of adult males. The study findings of (Yao &
Mills 2016) reveal the intracellular antioxidant action of GSH that effectively improves
sperm morphology and motility in adult males. The antioxidant genes including GST
(glutathione S-transferase) and GPX (glutathione peroxidase) play a pivotal role in
normalizing the sperm function and spermatogenesis in males (Yu & Huang 2015).
However, disruption of these genes substantially increases the risk of subfertility,
oligozoospermia, oligoasthenoteratozoospermia, and reduced sperm quality.
The adverse impact of functional polymorphisms and reactive oxygen species on
GST and GPX leads to the establishment of infertility pattern in the affected males.
However, the impact of glutathione therapy on the functionality of GST and GPX genes is
not yet well explored by the scientific community. Glutathione substantially improves
mitochondrial DNA function and proves to be a co-factor for numerous vitamins and
enzymes. However, the assessment of the biochemical pathways of glutathione metabolism
is beyond the scope of the presented study that effectively explores the impact of
glutathione oral therapy on the sperm motility, morphology, and concentration in adult
males (Pizzorno 2014). The study by (Ahmadi, Bashiri, Ghadiri-Anari, & Nadjarzadeh,
2016) advocates the need for semen analysis in the context of evaluating motility,
morphology, and concentration of the human sperms. The reduction in antioxidant semen
capacity substantially increases the risk of sperm abnormalities including
oligoasthenoteratozoospermia, teratozoospermia (i.e. disfigured sperm morphology),
asthenospermia (i.e. decreased sperm motility), and oligozoospermia (i.e. decreased sperm
concentration) (Ahmadi et al. 2016). Since glutathione is one of the several antioxidants in
human serum, its elevated concentration is believed to improve sperm physiology and
concentration in adult males.
The study by (Majzoub & Agarwal 2017) reveals the potential of glutathione to
effectively protect the human sperms from the adverse impact of lipid peroxidation. This
protective effect of glutathione improves the sperm motility and viability to a considerable
extent. Glutathione reductase extends protective effect over the sperm membrane attributes
and tail-beat frequency. Some studies reveal the poor absorbance of GSH across the
intestinal tract that reciprocally impacts its bioavailability and therapeutic outcomes
(Majzoub & Agarwal 2017). Research intervention by (Lombardo et al. 2011) reveals the
limited evidence regarding the beneficial outcomes of antioxidant therapies in male affected
with infertility. In-vitro assessment reveals the potential of GSH in terms of safeguarding
the ROS-based DNA loss in adult males. Similarly, the pre-clinical study by (Tuncer et al.
2010) reveals limited spermatic DNA damage under the impact of GSH administration.
Study outcomes of (Majzoub & Agarwal 2018) evidently describe the beneficial outcomes
of several antioxidants on the male fertility pattern. However, prospective studies require
execution on a wider scale in the context of determining an optimal antioxidant therapy to
facilitate the safe and effective treatment of male fertility in clinics and hospital settings.
Indeed, evidence-based findings reveal research gaps in relation to glutathione therapy and
enhancement of semen attributes in adult males. Accordingly, the presented study is based
on the following objective and hypothesis.
Aim/Objective: The presented prospective randomized placebo-controlled study
evaluates the effectiveness of glutathione therapy in elevating the overall semen
functionality and sperm count. The quantitative study explores the potential of orally
administered glutathione in terms of improving the sperm motility, concentration, and
morphology in adult males.
Hypothesis: Orally administered glutathione is an effective therapy for enhancing
the sperm concentration, morphology, and motility in married infertile males.
Null Hypothesis: Glutathione does not improve the semen parameters in adult
males.
Background Literature
The increased quantity of white blood cells (i.e. leukocytes) and immature sperm
cells in the sperm cells substantially elevate the concentration of reactive oxygen species.
Inflammation, infection, varicocele, and prolonged sexual abstinence includes some of the
significant causes that substantially elevate leucocyte count across the sperm cells
(Walczak–Jedrzejowska, Wolski & Slowikowska–Hilczer 2013). Glutathione is a non-
enzymatic anti-oxidant that exhibits protective effects on semen along with other
antioxidants including copper, selenium, zinc, carnitine, coenzyme Q10, pantothenic acid,
and vitamins B complex, C, E, and A. The elevated antioxidant activities lead to reduced
sperm survival in the affected males. Studies reveal glutathione as an intracellular thiol with
elevated abundance. Glutathione during oxidative stress releases its reconstructed thiol
groups in the context of exhibiting its anti-oxidant effects (Walczak–Jedrzejowska, et al.,
2013). Glutathione prevents lipid oxidation of cell membranes while concomitantly
minimizing the configuration of free oxygen.
Reduction in glutathione quantity in male cells destabilizes the middle spermatozoa
region that results in the development of sperm motility disorder (Walczak–Jedrzejowska, et
al., 2013). Studies reveal sustained modification in sperm parameters following the
administration of glutathione therapy to infertile adult males affected with urogenital
inflammation or unilateral varicocele. N–acetylcysteine is a glutathione precursor that
enhances that effectively enhances sperm motility and reduces the extent of sperm DNA
deterioration. The concomitant administration of pantothenic acid with glutathione
effectively improves oxidative stress of the sperm cells (Walczak–Jedrzejowska, et al.,
2013). Substantial research gaps exist regarding the impact of antioxidant therapy on the
quality of sperm cells in the infertile adult males. Few research studies reveal the oral
glutathione-based enhancement of sperm concentration in infertile men (Walczak–
Jedrzejowska, et al., 2013). However, the studies reveal the potential of oral antioxidants in
improving DNA integrity that substantially assists in improving the outcomes of assisted
reproduction.

Limited research interventions have utilized oxidative DNA damage, seminal

vitamin level and seminal oxidative stress as the selection criteria to evaluate the impact of
oral antioxidant therapy on the quality of sperm DNA. Some research studies reveal the
potential of oral antioxidant supplementation on the outcomes of various assisted
reproduction interventions (Walczak–Jedrzejowska, et al., 2013). This indicates that
administration of oral antioxidant therapy to the subfertile men leads to a statistically
significant improvement in pregnancy and birth rates in couples who receive consecutive
cycles of assisted reproduction intervention. The scientific community is yet unable to
define an antioxidant dose to effectively treat infertility in adult males. Prospective research
studies need to be organized in the context of determining the oxidative stress-based anti-
oxidant dose and mechanism of action to effectively customize infertility therapy for adult
males (Walczak–Jedrzejowska, et al., 2013).

The elevated concentration of glutathione is found in human spermatids and

spermatocytes. Glutathione not only scavenges free radicals but also proves to be a
coenzyme for glutathione peroxidase (Wagner, Cheng & Ko 2018). Glutathione effectively
interacts with glutathione peroxidase to remove free radicals from the sperm cells
(Meseguer et al. 2007). The assessment by reveals the sperm motility enhancement
following the concomitant administration glutathione, catalase, and vitamin E. However,
research studies also reveal the ineffectiveness of catalase and glutathione in terms of
safeguarding human spermatozoa from motility loss during the developmental phase of
human sperm. Oxidative trauma during semen processing elevates the risk of spermatozoa
deterioration. Glutathione’s mechanism in minimizing the spermatozoa injury is not
thoroughly explained in the evidence-based literature (Zini & Al-Hathal 2011).
The assessment by (Adewoyin et al. 2017) reveals the high risk of spermatozoa
membranes’ lipid peroxidation under the impact of their unsaturated fatty acid deposition.
The study also emphasizes the role of ROS and free radicals in the human reproduction
cycle. However, various internal and external factors negatively induce these free radicals
and reactive oxygen species in a manner to elevate the overall oxidative stress of the human
immune system. The antioxidant enzyme pathway of the seminal plasma exhibits the
capacity to antagonize this oxidative stress with the objective of maintaining the integrity
and functionality of the sperm cells (Adewoyin et al. 2017). The systematic assessment of
this oxidative stress is substantially required in the context of treating male infertility
through an appropriate therapeutic intervention. The researchers need to determine the
relationship between oxidative stress and GSH dosage requirements in the context of
streamlining infertility therapy for the male population. The GSH dosage adjustment needs
to be done in a manner to restore an equilibrium between ROS productivity and the activity
of free radicals (Adewoyin et al. 2017). The study by affirms the potential of sperm
capsular selenoprotein in maintaining the integrity of spermatozoa membrane. Elevated
ROS concentration under the impact of oxidative stress degrades the viability of
spermatozoa membrane. Researchers need to determine the impact of GSH therapy on the
structure and function of sperm capsular selenoprotein of the spermatozoa membrane.
Oral antioxidant therapy for asthenoteratozoospermia substantiates the requirement
of co-administration of multiple antioxidants (like vitamin E and selenium) in the context of
improving the fertility pattern of the treated patients (Moslemi & Tavanbakhsh 2011).
However, combined therapy of MSH with other antioxidants for male infertility treatment
has not been established in the scientific literature. The assessment by (Tirumala Vani et al.
2010) reveals a reciprocal relationship between idiopathic male fertility and GSTM1
(glutathione S-transferase Mu-1) gene polymorphism. However, prospective studies need
execution in the context of evaluating a deterministic relationship between GSTM1 and
GSH oral therapy. Indeed, the thorough understanding and assessment of GSH pathways
and their effectiveness to overcome infertility are substantially required to configure an
effective GSH oral therapy for the target population.
The study by (Atig et al. 2012) reveals the limited productivity of GSH in men
affected with azoospermia and oligozoospermia in comparison to individuals with normal
semen characteristics. Furthermore, the research studies also reveal the GSH capacity to
antagonize the cytotoxic aldehydes that degrade the plasma membrane of sperm through
lipid peroxidation (Atig et al. 2012). The researchers need to spectrophotometrically
evaluate the GSSG (oxidized glutathione) and GSHr (GSH reductase) levels in the context
of optimizing oral GSHt (Total Glutathione) therapy for overcoming the excessive
production of reactive oxygen species in the infertile men. The presented research study is
the initial step that attempts to determine the therapeutic effectiveness of oral GSH therapy
in terms of stabilizing the seminal parameters. However, the study does not explore the
mechanisms and biochemical pathways that effectively communicate with each other to
improve the sperm enhancement potential of GSH in the target population. The presented
study and associated findings substantially elevate the scope of conducting prospective
trials to undertake molecular studies for understanding the mechanism of GST action in
relation to infertility treatment in the male population.
Material and Methods
Participants
The presented prospective randomized placebo-controlled study was conducted in
Saladin province of Samarra city (Iraq) between Jan 2017 to Mar 2018. The study deployed
51 infertile male subjects who exhibited normal female factor for the administration of oral
glutathione (250mg sachets) for a tenure of 6-months. However, 50 infertile males received
the placebo treatment. Entire males who participated in the research intervention had the
normal female factor in relation to the fertility parameters. The patients affected with
chronic diseases including mumps, hydrocele, neoplasm, varicocele, trauma from prolonged
riding, neoplasm, varicocele, vas deferens obstruction, hypospadias, and genital tract
infection were summarily excluded from the presented research intervention. Furthermore,
infertile males who had recently received infertility treatment were also not allowed to
participate in the research study. The male participants between the age group of 35-40
years were included in the research intervention.
Informed Consent
Informed consent was obtained from the entire study subjects while categorically
explaining them the interventions, objectives, and outcomes. Data collection from study
participants was undertaken after the acquisition of the informed consent.
Interventions
Oral administration of GSH sachets (BioTADplus) to the study participants (i.e. the
treatment group only) was undertaken for a period of 6-months. The placebo group did not
receive the GSH treatment for the same time. However, placebo group participants
remained unaware of the treatment intervention because of the single-blinded nature of the
study intervention. Sampling, Data Collection and Analysis
Blood and semen samples were obtained from the treatment and placebo groups at 0
weeks, 3 months, and 6 months period. Blood sampling was performed with the core
objective of detecting the GSH concentration. Addition of a precipitating solution and
centrifugation were performed in the context of evaluating the seminal plasma GSH by
utilizing the Ellman method.
Data collection from study participants was undertaken after informed consent
through interactive interviews. The participants shared the significant information related to
their social habits, marriage duration, occupation, and age during the interview session.
 Data analysis was undertaken through SPSS 15.0 in the windows interface. Mann
Whitney U-test and unpaired t-test were systematically utilized for assessing the data
significance for P value<0.05. The genital organs of the entire study participants were
examined to evaluate their size of vas deferens, epididymis, and testes while concomitantly
assessing/ruling-out the presence of a varicocele.
Results
The below-mentioned tables present the outcomes obtained at 0 weeks, 3 months,
and 6 months of oral GSH and placebo treatment administration.
Table – 1 (Participants’ age and semen parameters recorded at 0-week)
Placebo group (n=50) GSH group ( n=51) Domains
35.82+-4.92 35.21+-5.18 Age
2.21+-0.92 2.25+-0.85 Semen Volume
51.5+-8.2 50.2+-8.1 Semen concentration
27.5+-2.5 27.0+-2.6 % of motility
9.5+-3.1 9.8+-3.2 Morphology

No significant difference regarding the semen parameters was recorded between the
two groups at the beginning of the study intervention.
Table – 2 (Seminal plasma GSH levels in mg/dl)

6 months 3 months 0 weeks Seminal

GSH level
mg/dl
Placebo GSH group Placebo GSH group Placebo GSH group
n=50 n=51 n=50 n=51 n=50 n=51
1.52 (0.27- 4.58 (2.55- 1.55 (0.26- 4.55 (2.58- 1.58 (0.26- 1.52 (0.25-
7.02) 7.25) 7.04) 7.20) 7.02) 6.92)

rd
The outcomes reveal serum plasma GSH elevation in the treatment group at 3 and
th
6 months of the oral GSH therapy. P-value was recorded to be less than 0.001 during this
tenure.
Table – 3 (GSH levels in the blood)

6 months 3 months 0 weeks GSH level

mg/g Hb
Placebo GSH group Placebo GSH group Placebo GSH group
n=50 n=51 n=50 n=51 n=50 n= 51
14.78 (0.80- 15.25 (2.28- 14.8 (0.89- 15.2 (2.26- 14.8 (0.86- 14.5 (0.85-
29.2) 26.2) 29.1) 25.4) 29.20) 28.2)

The outcomes at 0 weeks, 3 months, and 6 months did not reveal any significant
difference between blood GSH levels of the treatment and placebo groups.
Table – 3 (Semen parameters in response to the oral GSH/placebo therapy)

6 months 3 months Parameters

Placebo n=50 GSH group n=51 Placebo n=50 GSH group n=51
3.5 38.4 3.5 38.2 % of motility
4.6 27.2 4.5 26 % of morphology
1.6 24.2 1.8 24 % of sperm
concentration

The following outcomes regarding the semen parameters were recorded after
therapeutic administration of oral GSH to the treatment group.

1. The significant p-value of 0.01 for the sperm motility was recorded at 3rd and 6th
months of treatment for the GSH group.
2. The significant p-value for the sperm morphology was recorded as 0.03 for the
GSH group at 3rd and 6th months of oral GSH treatment.
 3. The significant p-value of 0.01 for the sperm concentration was recorded for the
GSH group at 3rd and 6th months of oral GSH administration.
The study outcomes revealed oral glutathione therapy as an effective treatment for
improving the pattern of sperm concentration, morphology, and motility of the selected
subjects.
Discussion
Male infertility is a direct outcome of inconsistencies in sperm morphology,
motility, and concentration. Immature oocytes significantly lead to premature chromosome
condensation across the sperm cell lines. The study outcomes by (Meybodi, Mozdarani,
Moradi, & Akhoond, 2012) reveal the capacity of GSH intervention to reduce the oxidative
stress of the sperm cells that resultantly improves their motility and increases the scope of
fertilization. The outcomes of the presented study effectively concord with the evidence-
based findings that reveal the protective effect of GSH on sperm motility and maturation.
However, the presented study does not reveal the GSH mechanism that safeguards seminal
plasma and sperm from oxidative stress. The study by (Meybodi et al. 2012) reveals a
higher risk of oxidative stress-based disruption of sperm cell line in the infertile males who
reportedly undergo glutathione transferase enzyme mutation. Prospective studies should be
conducted to understand the impact of oral GSH therapy on the functionality, structure, and
configuration of glutathione transferase enzyme of the infertile males.
Numerous research studies reveal both positive and negative correlations (i.e.
controversial findings) between the glutathione peroxidase activity in seminal plasma and
sperm motility/quality pattern (Macanovic et al. 2015). These outcomes substantiate the
requirement of assessing the seminal plasma in the context of determining probable
mutations in the antioxidative defense enzymes across the sperm cell lines. This diagnostic
intervention is required to identify the defects or mutations in protein expressions that
directly result in male infertility. Accordingly, researchers can optimize the oral GSH
dosage to effectively overcome the inconsistencies in antioxidative defense enzyme for
improving the overall semen quality. The presented study outcomes prove to be the ladder
in this direction that the researchers need to utilize for evaluating numerous semen
parameters on a wider scale to effectively generalize the utilization of GSH therapy for the
infertile males.
The assessment by (Agarwal, Virk, Ong, & Plessis, 2014) reveals the potential of
the excess residual cytoplasm of the deteriorated immature spermatozoa to disrupt the
sperm morphology and motility. The excess residual cytoplasm of the degraded
spermatozoa utilizes the hexose-monophosphate shunt to effectively induce the NADPH
system. This resultantly hinders the ROS equilibrium and increases the oxidative stress that
results in degradation of sperm quality and fertilization capacity of the adult males
(Agarwal et al. 2014). The presented study reveals the positive influence of oral GSH
therapy on sperm morphology. However, prospective research studies require execution
with the objective of understanding the impact of oral GSH therapy on NADPH induction
pattern across the deteriorated spermatozoa. This will effectively help in determining the
biochemical pathways interfered by the oral GSH therapy in the infertile males.
The analysis by (Hsieh, Chang & Lin 2006) reveals an insignificant correlation
between seminal quality and glutathione peroxidase activity. Study outcomes advocate the
need for assessing seminal MDA (malondialdehyde) concentration to identify the extent of
degradation in sperm motility and concentration in the infertile males. The presented study
effectively reveals a positive correlation between the sperm concentration and oral GSH
administration. However, the study does not identify the mechanism of GSH interaction
with seminal malondialdehyde in the study subjects. The researchers, therefore, require
conducting prospective analysis to evaluate the impact of oral GSH in MDA concentration
(as a sperm concentration parameter) in the infertile married males. The assessment by
(Yeste et al. 2013) reveals the constructive influence of reduced-glutathione on the
nucleoprotein pattern of the deteriorated and underdeveloped spermatozoa. The findings,
therefore, indicate the need for GSH administration for the enhancement of sperm viability
in the infertile males. The presented study indicates the linear improvement in semen
parameters following the GSH administration. However, greater analysis of the associated
mechanisms is required to authenticate and generalize the positive correlation between oral
GSH therapy and extended semen parameters and biomolecular pathways.
 Conclusion
The presented study effectively evaluated the effectiveness of oral GSH therapy on
semen parameters including sperm motility, morphology, and concentration. The findings
categorically reveal the therapeutic advantage of oral GSH intervention in terms of
improving the selected semen parameters in the infertile males. The study limitations are
based on the restricted sample size and absence of a thorough analysis of biochemical
interactions of GSH with the deteriorated sperm cells of the selected males. The researchers
need to replicate the study on a wider scale while considering the oral absorption and
bioavailability of the oral GSH in the male population. The prospective assessment of GSH
effects on various semen parameters including MDA concentration, NADPH system,
glutathione peroxidase activity, sperm nucleus structure, and GSHr/GSSG concentration is
necessarily required to effectively optimize oral GSH therapy for the infertile males.
Furthermore, GSH impact on ROS and oxidative stress requires further exploration while
evaluating the associated biomolecular pathways. The researchers also need to investigate
the scope of co-administering other antioxidants like carnitine, selenium, and vitamin B
complex with oral GSH therapy to minimize the prevalence of male infertility in the
selected population.

References
Adeoye, O, Olawumi, J, Opeyemi, A & Christiania, O 2018, 'Review on the role of glutathione on
oxidative stress and infertility', JBRA Assist Reprod, vol 22, no. 1, pp. 61-66, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844662/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844662/ >.
Adewoyin, M, Ibrahim, M, Roszaman, R, Isa, MLM, Alewi, NAM, Rafa, AAA & Anuar, MNN
2017, 'Male Infertility: The Effect of Natural Antioxidants and Phytocompounds on Seminal
Oxidative Stress', Diseases, vol 5, no. 1, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456340/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456340/ >.
Agarwal, A, Virk, G, Ong, C & Plessis, SSD 2014, 'Effect of Oxidative Stress on Male
Reproduction', World J Mens Health, vol 32, no. 1, pp. 1-17, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026229/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026229/ >.
Ahmadi, S, Bashiri, R, Ghadiri-Anari, A & Nadjarzadeh, A 2016, 'Antioxidant supplements and
semen parameters: An evidence based review', Int J Reprod Biomed (Yazd), vol 14, no. 12, pp. 729-
736, < HYPERLINK "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203687/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203687/ >.
Atig, F, Raffa, M, Habib, BA, Kerkeni, A, Saad, A & Ajina, M 2012, 'Impact of seminal trace
element and glutathione levels on semen quality of Tunisian infertile men', BMC Urology, <
 HYPERLINK "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349502/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349502/ >.
Hsieh, YY, Chang, CC & Lin, CS 2006, 'Seminal malondialdehyde concentration but not
glutathione peroxidase activity is negatively correlated with seminal concentration and motility', Int
J Biol Sci, vol 2, no. 1, pp. 23-29, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1457038/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1457038/ >.
Lombardo, F, Sansone, A, Romanelli, F, Paoli, D, Gandini, L & Lenzi, A 2011, 'The role of
antioxidant therapy in the treatment of male infertility: an overview', Asian J Androl, vol 13, no. 5,
pp. 690-697, < HYPERLINK "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739574/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739574/ >.
Macanovic, B, Vucetic, M, Jankovic, A, Stancic, A, Buzadzic, B, Garalejic, E, Korac, A, Korac, B
& Otasevic , V 2015, 'Correlation between Sperm Parameters and Protein Expression of
Antioxidative Defense Enzymes in Seminal Plasma: A Pilot Study', Disease Markers, <
HYPERLINK "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323057/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323057/ >.
Majzoub, A & Agarwal, A 2017, 'Antioxidant therapy in idiopathic oligoasthenoteratozoospermia',
Indian J Urol, vol 33, no. 3, pp. 207-214, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508431/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508431/ >.
Majzoub, A & Agarwal, A 2018, 'Systematic review of antioxidant types and doses in male
infertility: Benefits on semen parameters, advanced sperm function, assisted reproduction and live-
birth rate', Arab Journal of Urology, pp. 113-124, < HYPERLINK
"https://www.sciencedirect.com/science/article/pii/S2090598X1730147X"
https://www.sciencedirect.com/science/article/pii/S2090598X1730147X >.
Meseguer, M, Martínez-Conejero , JA, Muriel , L, Pellicer , A, Remohí , J & Garrido , N 2007, 'The
human sperm glutathione system: a key role in male fertility and successful cryopreservation', Drug
Metab Lett, vol 1, no. 2, pp. 121-126, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pubmed/19356030"
https://www.ncbi.nlm.nih.gov/pubmed/19356030 >.
Meybodi, AH, Mozdarani, H, Moradi, SZ & Akhoond, MR 2012, 'Importance of sperm gluthatione
treatment in ART', J Assist Reprod Genet, vol 29, no. 7, pp. 625-630, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401252/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401252/ >.
Moslemi, MK & Tavanbakhsh, S 2011, 'Selenium–vitamin E supplementation in infertile men:
effects on semen parameters and pregnancy rate', Int J Gen Med, pp. 99-104, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048346/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048346/ >.
Pizzorno, J 2014, 'Glutathione!', Integr Med (Encinitas), vol 13, no. 1, pp. 8-12, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684116/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684116/ >.
Tirumala Vani , G, Mukesh, N, Siva, PB, Rama, DP, Hema, PM, Usha, RP & Pardhanandana , RP
2010, 'Role of glutathione S-transferase Mu-1 (GSTM1) polymorphism in oligospermic infertile
males', Andrologia, vol 42, no. 4, pp. 213-217, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pubmed/20629642"
https://www.ncbi.nlm.nih.gov/pubmed/20629642 >.
Tuncer, PB, Bucak , MN, Büyükleblebici , S, Sarıözkan , S, Yeni, D, Eken, A, Akalın , PP, Kinet ,
H, Avdatek , F, Fidan, AF & Gündoğan , M 2010, 'The effect of cysteine and glutathione on sperm
and oxidative stress parameters of post-thawed bull semen', Cryobiology, vol 61, no. 3, pp. 303-307,
< HYPERLINK "https://www.ncbi.nlm.nih.gov/pubmed/20951122"
https://www.ncbi.nlm.nih.gov/pubmed/20951122 >.
Wagner, H, Cheng, JW & Ko, EY 2018, 'Role of reactive oxygen species in male infertility: An
updated review of literature', Arab J Urol, vol 16, no. 1, pp. 35-43, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922220/" \l "b0225"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922220/#b0225 >.
Walczak–Jedrzejowska, R, Wolski, JK & Slowikowska–Hilczer, J 2013, 'The role of oxidative stress
and antioxidants in male fertility', Cent European J Urol, vol 66, no. 1, pp. 60-67, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921845/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921845/ >.
Yao, DF & Mills, JN 2016, 'Male infertility: lifestyle factors and holistic, complementary, and
alternative therapies', Asian J Androl, vol 18, no. 3, pp. 410-418, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854092/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854092/ >.
Yeste, M, Flores, E, Estrada , E, Bonet , S, Rigau , T & Rodríguez-Gil , JE 2013, 'Reduced
glutathione and procaine hydrochloride protect the nucleoprotein structure of boar spermatozoa
during freeze-thawing by stabilising disulfide bonds.', Reprod Fertil Dev, vol 25, no. 7, pp. 1036-50,
< HYPERLINK "https://www.ncbi.nlm.nih.gov/pubmed/23089308"
https://www.ncbi.nlm.nih.gov/pubmed/23089308 >.
Yu, B & Huang, Z 2015, 'Variations in Antioxidant Genes and Male Infertility', Biomed Res Int, <
HYPERLINK "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651646/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651646/ >.
Zini, A & Al-Hathal, N 2011, 'Antioxidant therapy in male infertility: fact or fiction?', Asian J
Androl, vol 13, no. 3, pp. 374-381, < HYPERLINK
"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739339/"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739339/ >.