Physiology of Male Infertility | Seeds of Innocence

Patho-physiology of male
infertility & role of
micro nutrient in
management of male
infertility.

DR.GAURI AGARWAL
DIRECTOR IVF
SEEDS OF INNOCENCE IVF CENTRE-
COLLABORATED WITH UNIVERSITY
OF GENT.BELGIUM

Male Infertility
 Infertility is considered due to ′male factor′ when an
alteration in sperm concentration and/or motility
and/or morphology is present in at least one sample of
two sperm analyses.
 In 50% of involuntarily childless couples, a male
infertility associated factor is found together with
abnormal semen parameters.
WHO Manual for the Standardized Investigation and Diagnosis of the
Infertile Couple. Cambridge: Cambridge University Press, 2000.

Overview of spermatogenesis
• Takes place within the seminiferous tubules.
• Immature germ cells undergo division,
differentiation, & meiosis to give rise to
spermatids.
• Mature spermatids are released from the Sertoli
cells & enter epididymis.
• During passage through epididymis, spermatids
undergo biochemical changes to become the
motile spermatozoa capable of fertilization.

Regulation of spermatogenesis
• LH targets Leydig cell to stimulate secretion of
testosterone, which acts on androgen receptors
in the seminiferous epithelium to control
spermatogenesis.
• FSH targets receptors within the Sertoli cell to
regulate spermatogenesis by stimulating the
production of numerous Sertoli cell factors.
• Initiation and maintenance of quantitatively
normal spermatogenesis rely on the balance of
the hypothalamo-pituitary-testis axis.

WHO reference
values for human semen, 2010
World Health Organization. WHO Laboratory Manual for the Examination and Processing of
Human Semen. 5th edn. WHO, 2010

Abnormal Semen
Oligozoospermia: < 15million spermatozoa/ml
Asthenozoospermia: < 32% motile spermatozoa
Teratozoospermia: < 4% normal forms.
Azoospermia
World Health Organization. WHO Laboratory Manual for the Examination and Processing of
Human Semen. 5th edn. WHO, 2010

Causes of male factor
Infertility

Male infertility factors
in10,469 patients
The EAU Guideline Panel on Male Infertility

Testicular deficiency
 Usually caused by conditions other than
hypothalamic-pituitary disease & obstructions of
the male genital tract.
 Commoest form of male infertility.
 Present as severe oligo-astheno-teratozoospermia
(OAT )or non-obstructive azoospermia (NOA).
 Hypergonadotrophic hypogonadism is usually
present.

Testicular deficiency: Etiology
The EAU Guideline Panel on Male Infertility.20112

Varicocele
 Present in 11.7% of adult men and in 25.4%
of men with abnormal semen analysis
 A common abnormality with following
implications:
Failure of ipsilateral testicular growth and
development
Symptoms of pain and discomfort
Infertility.

Varicocele
• Associated with progressive testicular
damage.
• Results in increased sperm DNA
damage, secondary to oxidative stress.
• Varicocelectomy can reverse sperm
DNA damage.
• Surgery for subclinical varicoceles is
not recommended. Oral antioxidants
improve sperm functions.

Obstructive Azoospermia (OA)
 Inability to detect both spermatozoa and
spermatogenetic cells in semen and post-
ejaculate urine due to bilateral obstruction
of the seminal ducts.
 OA is less common than NOA
 Occurs in 15-20% of men with azoospermia.
 Present with normal FSH, normal size testes
and epididymal enlargement.

Obstructive Azoospermia (OA):
Classification

Hypogonadism
 Characterized by impaired testicular function,
which may affect spermatogenesis and/ or
testosterone synthesis.
 Categories:
 Primary (hypergonadotrophic) hypogonadism due to testicular
failure
 Secondary (hypogonadotrophic) hypogonadism caused by
insufficient gonadotrophin-releasing hormone (GnRH) and/or
gonadotrophin (FSH, LH) secretion.
 Androgen insensitivity (end-organ resistance).

Cryptorchidism (Undescended
testis )
 Most common congenital abnormality of the
male genitalia found in 2-5% of newborn
boys.
 At the age of 3 months, spontaneous descent
occurred in most boys, and the incidence of
cryptorchidism fell to 0.9% and 1.7%, in the >
2500 g and < 2500 g group, respectively
 Causes (multifactorial):
• Endocrine disruption in early pregnancy
• Gene defects

Cryptorchidism
 Paternity with unilateral cryptorchidism:
almost equal (89.7%) to that in men without
cryptorchidism (93.7%).
 Bilateral cryptorchidism:
– Oligozoospermia can be found in 31% and
azoospermia in 42%.
– Rate of paternity is only 35-53%.
EAU Guideline Panel on Male Infertility ,2012

Male Accessory Gland
Infections (MAGIs)
Potentially curable causes of male infertility
 Urethritis: Chlamydia trachomatis,
Ureaplasma urealyticum, and Neisseria
gonorrhoea
 Prostatitis: Acute & Chronic bacterial
prostatitis (abp) and prostatic abscess, non-or
abacterial prostatitis (nbp) & prostatodynia
 Orchitis and Epididymitis

Male Accessory Gland
Infections (MAGIs)
• Effects of chronic prostatitis on sperm density,
motility and morphology are under debate
• Reactive oxygen species might be increased in chronic
urogenital infections associated with increased
leukocyte numbers.
• Although antibiotic for MAGI might provide
improvement in sperm quality, therapy does not
necessarily enhance the probability of conception.

Disorders of Ejaculation
 Disorders of ejaculation are uncommon, but
important, causes of male infertility.
 Can be either organic or functional:
– Anejaculation
– Anorgasmia
– Delayed ejaculation
– Retrograde ejaculation
– Premature ejaculation (may not impair fertility, provided intravaginal
ejaculation occurs.)
– Painful ejaculation

Disorders of Ejaculation
Retrograde ejaculation:
 It is the total, or sometimes partial, absence of
antegrade ejaculation as a result of semen passing
backwards through the bladder neck into the bladder.

Idiopathic oligoasthenoteratozoospermia
(iOAT)
 A common cause of male infertility.
 It is characterized by -low sperm count
with a high percentage of slow-moving and
abnormal sperms.
 30-4O% of cases are considered idiopathic.
 May be explained by : endocrine disruption
as a result of environmental pollution,
reactive oxygen species or genetic
abnormalities
Contd…

Idiopathic
oligoasthenoteratozoospermia:i
OAT
 Although hormonal abnormalities are not always
evident, iOAT is sometimes associated with lower
serum testosterone and higher serum estradiol,
LH and FSH levels.

Investigations
 Semen analysis (at least two)
 Hormonal determinations
 Post-ejaculatory Urinalysis
 Ultrasonography
 Genetic evaluation
 Some cases may require specialized
clinical tests on semen and sperm.

Hormonal Determinations
 An initial endocrine evaluation should include a
serum testosterone and FSH if there is:
–An abnormally low sperm concentration, especially if less
than 10 million/ml;
– Impaired sexual function; or
– Other clinical ﬁndings suggestive of a speciﬁc endocrinopathy
 If the testosterone level is low, a repeat total &
free testosterone, serum LH and prolactin levels
should be obtained.
 .

Hormonal Determinations
 Testicular deficiency hypergonadotrophic
hypogonadism: : FSH and LH and testosterone.
 A normal serum FSH level does not
guarantee normal spermatogenesis.
 Marked elevation of the serum FSH level
to more than two times the upper limit of
normal is diag-nostic of abnormal
spermatogenesis.

Post-ejaculatory Urinalysis
• Should be performed in patients with
– ejaculate volumes of less than 1 ml, except in
patients with bilateral vasal agenesis or
– clinical signs of hypogonadism.
• Signiﬁcant numbers of sperm must be
found in the urine of patients with low
ejaculate volume oligospermia in order to
suggest the diagnosis of retrograde
ejaculation.

Testicular Biopsy
 Indications
Azoospermia or extreme OAT in the presence
of a normal testicular volume and normal FSH
levels.
To exclude spermatogenic failure.
 The biopsy is aimed at differentiating
between testicular insufficiency and
obstruction of the male genital tract.

Ultrasonography
 Transrectal ultrasonography is indicated in
azoospermic patients with palpable vasa and
low ejaculate volumes to determine if
ejaculatory duct obstruc-tion exists.
 Some experts recommend TRUS for
oligospermic Patients with low volume
ejaculates, palpable vasa, & normal
testicular size, to determine if ejaculatory
duct ob-struction is present.

Genetic Evaluation
 Men with non-obstructive azoospermia and
severe oligo-Spermia should be informed of
the potential genetic abnormalities
associated with azoospermia or severe
oligospermia.
 Karyotyping and Y-chromosome analysis
should be offered to the male Who has
nonobstructive azoospermia or severe
oligospermia prior to performing ICSI.

Endogenous Antioxidants
Seminal plasma contains three main
enzymatic antioxidants:
 Superoxide dismutase (SOD), catalase, and
glutathione peroxidase/glutathione reductase
(GPX/GRD).
 Non enzymatic antioxidants : ascorbate, urate,
vitamin E, pyruvate, glutathione, albumin, vitamin
A, ubiquitol, L carnitine, taurine, and hypotaurine.
 Spermatozoa possess primarily enzymatic
antioxidants :with SOD most predominant.

Mammalian sperm cells
 Mammalian sperm cells present highly
specific lipidic composition, high content
of polyunsaturated fatty acids, and
sphingomyelins.
 Lipid components of sperm membranes are
involved in:
– regulation of sperm maturation,
spermatogenesis, capacitation, acrosome
reaction and eventually in membrane fusion.

Vulnerability of sperm to OS
 Despite the low oxygen tensions that
characterize the testicular micro-
environment, this tissue remains
vulnerable to oxidative stress due to:
– Abundance of highly unsaturated fatty
acids.
– Presence of potential reactive oxygen
species (ROS)-generating systems (from the
mitochondria and a variety of enzymes.)

Vulnerability of sperm to OS
 Spermatozoa are particularly susceptible
to OS-induced damage because
 Their plasma membranes contain large quantities of
polyunsaturated fatty acids (PUFAs)
 Their cytoplasm contains low concentrations of
scavenging enzymes.
 the intracellular antioxidant enzymes cannot protect the
plasma membrane that surrounds the acrosome and the
tail.

The role of oxidative stress in idiopathic
oligoasthenoteratozoospermia
 At physiologic levels, ROS are essential
for:
Normal reproductive function,
Metabolism of prostanoid,
Regulation of vascular tone,
Sperm capacitation (final maturation of sperm)
and acrosome reaction (penetration of sperm
head into egg ).
At higher concentrations, ROS exert negative
effects.
Contd…

Origins of oxidative stress in
semen
 Main source of ROS production in
seminal plasma:
Leukocytes
Immature spermatozoa
Morphologically abnormal spermatozoa

Origins of oxidative stress in
semen
Human Reproduction Update, Vol.14, No.3 pp. 243–
258, 2008

Mechanism of Increased Production of
ROS by Abnormal Spermatozoa
Vol. 23, No. 6, November/DeceJournal of Andrologymber 2002
 When spermatogenesis is impaired,
spermatozoa are released from the
germinal epithelium carrying surplus
residual cytoplasm.
 Retention of residual cytoplasm by
spermatozoa is positively correlated with
ROS generation via mechanisms that may
be mediated by the cytosolic enzyme G6PD.

Effect of oxidative stress (OS)
 40-80% of non selected infertile patients have high
levels of free oxygen radical in semen.
 Infertile men have higher free radicals than fertile
men.
 ROS attacks poly unsaturated fatty acid
(PUFA)PUFA in the cell membrane, leading to a
cascade of chemical reactions ----lipid peroxidation.
Contd…

Antioxidants & oxidative stress in seminal
plasma & their role in infertility
Journal of Andrology, Vol. 25, No. 1, January/February 2004

Pathology behind OS leading to
infertility.
• Reduced sperm motility:
– ROS-induced peroxidation of the sperm membrane decreases
its flexibility &tail motion.
– Damage to mitochondria, decreasing energy availability, may
also impede sperm motility.
• Sperm DNA damge:
– Free radicals damage sperm DNA by attacking the purine and
pyrimidine bases, resulting in passage of defective paternal
DNA to the conceptus.

Pathology behind OS leading to
infertility.
• During natural conception or routine
IVF, oxidative damage to the sperm
membrane will normally block
fertilization.
• During IVF-ICSI this natural barrier to
fertilization is lost and sperm containing
signiﬁcantly damaged DNA can still
achieve fer-tilization .

Effect of Oxidative Stress
OS
lipid peroxidation of sperm membrane
By altering membrane integrity, ROS impair
sperm motility and morphology
Can lead to infertility

Antioxidants for male subfertility.
Cochrane review,(2011)
 They included randomised controlled trials
comparing any type or dose of antioxidant
supplement (single or combined) taken by the
male partner of a couple seeking fertility
assistance with placebo, no treatment or
another antioxidant.
 34 trials with 2876 couples in total were
included.

Antioxidants for male subfertility. Cochrane
review ,(2011)
 Conclusions:
The evidence suggests that antioxidant
supplementation in subfertile males may improve
the outcomes of live birth and pregnancy rate
for subfertile couples undergoing ART cycles.
Cochrane Database Syst Rev. 2011 Jan 19;(1):CD007411

Effect of micronutrients on
sperm dysfunction
• Many small,uncontrolled studies have shown a
significant improvement in semen parameters
following different doses and types of antioxi-
dant therapy.
• Commonly studied antioxidants : vitamin C,
vitamin E, sel-enium, zinc, glutathione, L-carnitine
and N-acetyl cysteine.
• The randomized controlled trials demonstrate
that anti-oxidants has a beneficial effect (semen
parameter improvements).
• Asian Journal of Andrology (2011) 13, 374–381

Effect of micronutrients on
sperm motility
• Antioxidants increase sperm motility:
• A randomized double-blind controlled trial has
shown that vitamin E administered orally (300
mg/day) results in improved sperm motility.
• Another study has shown that incubation of sperm
samples from asthenozoospermic infertile males for
24 h in Ham’s F-10 medium with coenzyme Q10
improves sperm motility.
• Lenzi et al reported that oral supplementation of 2-
3 g/day of carnitines for >2 months improved sperm
concentration and motility.
Indian J Med Res 129, April 2009,
pp 357-367

Role of antioxidants in
preventing DNA damage
• Daily oral supplementation of 1 g
vitamins C and E for two months is
reported to reduce the number of
spermatozoa with DNA fragmentation,.
• The same group also showed
improvement of clinical pregnancy and
implantation rates after antioxidant
treatment compared with the pre-
treatment outcomes of ICSI.
• Indian J Med Res 129, April 2009, pp 357-367

Role of antioxidants in
preventing cryodamage
• Sperm freezing and thawing procedures
cause a significant and irreversible
depression of motility and metabolic
activity of sperm along with disruption of
plasma membrane104
• Park et al have shown thatvitamin E (10
mmol/l) and rebamipide (300 mmol/l)
decreased the cryodamage during the
freeze-thaw procedure and improve post-
thaw motility. Indian J Med Res 129, April 2009, pp 357-367

Antioxidant in smoking,
associated infertility
• Tobacco smoke consists ofcompounds such as
alkaloids, nitrosamines and inorganic molecules,
and many of these substances are reactive
oxygen.
• Significant positive association has been reported
between active smoking and sperm DNA
fragmentation as well as
• axonemal damage and decreased sperm count.
• Antioxidants improve semen quality in smokers.
• Indian J Med Res 129, April 2009, pp 357-367

L Carnitine
 Carnitine is a water-soluble antioxidant
mostly derived from the human diet;
approximately 25% is synthesized from
lysine and methionine.
 Carnitine is an essential co-factor of
fatty acid metabolism.
 Highest level of L-carnitine in the man is
found in epididymal fluid.

L-Carnitine
 In epididymis, the free L-carnitine is taken
up from the blood plasma, transported into
the epidid-ymal ﬂuid & into the
spermatozoa, & accumulated as both free
and acetylated L-carnitine.
 It provides the primary fuel for sperm
motility via post-testicular effects.
 It is involved in maturation of sperm.

 Protects sperm DNA and cell membranes
from ros-induced damage & apoptosis.
 Carnitines function in mitochondria:
 Enhance cellular energetics in mitochondria by facilitating the
entry and utilization of free fatty acids within the mitochondria
 restore the phospholipid composition of mitochondrial
membranes by decreasing fatty acid oxidation .
 modulation of acyl-CoA / CoA ratio, storage ofenergy as
acetylcarnitine,
Contd…
L-Carnitine

 Its levels has been correlated with
sperm parameters such as
concentration and motility, which relate
to higher fecundity.
 Supplementation of L carnitine
improves sperm motility, & sperm
concentration.
Contd…
L-Carnitine

Published trials on carnitine for
male infertility
Fertility and Sterility Vol. 85, No. 5, May 2006

Study on L-Carnitine/Acetyl-L-Carnitine for
Idiopathic and varicocele OAT
• Idiopathic and varicocele OAT patients
• Group 1; placebo, group 2 : oral L-carnitine (2 g/d) +
acetyl-L-carnitine (1 g/d), group 3: L-
carnitine/acetyl-L-carnitine + 1 x 30-mg cinnoxicam
suppository every 4 days. Drugs were administered
for 6 months.
• Group 2 :increased sperm patterns at 3 and 6 months
in idiopathic patients & in patients with grades I, II,
and III varicocele, but not in grades IV and V.
•

Study on L-Carnitine/Acetyl-L-Carnitine for
Idiopathic and varicocele OAT
• Group 3 :increased sperm parameters in all patients,
with the exception of grade V varicocele.
• Group 3: sperm patterns proved higher during
therapy than group 2.
• Pregnancy rates were 1.7% (group 1), 21.8% (group 2),
and 38.0% (group 3) (P <.01).
• L-carnitine/acetyl-L-carnitine + cinnoxicam
suppositories proved a reliable treatment for low-
grade varicoceles and idiopathic OATs
• Journal of Andrology, Vol. 25, No. 5, September/October 2004

Effects of carnitines in infertile patients with
prostato-vesiculo-epididymitis (PVE)
 Abacterial PVE infertile patients with
normal (<1106/ml, group A, n =34) or
abnormal (> 1106/ml, group B, n =20)
seminal WBC concentrations
 They received L-carnitine 1 g and acetyl-
carnitine 0.5 g twice/day for 3 months
followed by a wash-out period of 3
months.
 increased sperm forward motility and
viability in group A patients.
Human Reproduction Vol.16, No.11 pp. 2338–2342, 2001

Effects of carnitines in infertile patients with
prostato-vesiculo-epididymitis (PVE)
 increased only the percentage of viable
spermatozoa in group B patients.
 Within 3 months after the
discontinuation of carnitines, the rate of
spontaneous pregnancy in group A
patients was signiﬁcantly higher than
that of group B patients, being 11.7%
(4/34) compared with 0%.
Human Reproduction Vol.16, No.11 pp. 2338–2342, 2001

 It also functions as an antioxidant,
preventing lipid peroxidation of sperm
membranes.
 CoQ10 is well-absorbed by oral
supplementation.
 Mancini et al demonstrated high levels of
CoQ10 in human seminal fluid that
correlate positively with sperm count and
motility.
Coenzyme Q10 (Co-Q 10)
Contd…

 CoQ10 is a fat soluble compound found in
virtually every cell in the human body.
 Naturally occurring coenzyme involved in
electron transport in the mitochondria.
 Adequate amounts of CoQ10 are necessary
for ATP production.
 In sperm cells, CoQ10 is concentrated in
the mitochondrial mid-piece, where it is
involved in energy production.
Contd…

The effect of coenzyme Q10 on sperm
motility and function.
 A study was carried out to assess the effect of
CoQ-10 on sperm motility and function. When
sperm samples from 22 asthenospermic men were
incubated in vitro with CoQ10, significant
increases in motility were observed.
 CoQ10 (60 mg) was given to 17 infertile patients
for a mean 103 days, and although there were no
significant changes in standard sperm parameters,
there was a significant improvement in fertilization
rate (p<.0.05).
Lewin A Mol Aspects Med.1997; 18 Suppl:S213-9

Co Q10 in treatment of
idiopathic asthenozoospermia.
 In a double-blind randomized trial 60
infertile patients with idiopathic
asthenozoospermia underwent double-blind
therapy with coenzyme Q(10), 200
mg/day, or placebo.
 The study design was 1 month of run-in, 6
months of therapy or placebo, and 3
months of follow-up.

Co Q10 in treatment of
idiopathic asthenozoospermia.
 Coenzyme Q(10) and ubiquinol increased
significantly in both seminal plasma and sperm
cells after treatment, as well as spermatozoa
motility.
 Patients with a lower baseline value of motility
and levels of coenzyme Q(10) had a
statistically significant higher probability to
be responders to the treatment.
Fertil Steril. 2009 May;91(5):1785-92

 Research has shown CoQ10 given to
individuals with idiopathic decreased
sperm motility (asthenozoospermia)
raises CoQ10 levels in both seminal
plasma and sperm cells.
 Supplementation of Co Q10 improves
sperm motility.

Zinc
 Zinc plays an important role in normal testicular
development, spermatogenesis, and sperm
motility.
 It functions as a cofactor for many enzymes
involved in protein synthesis. It also has
antioxidant properties.
 Concentration of zinc in semen is high compared
with that of other body ﬂuids & tissues
Contd…

Zinc
 Chronic zinc deficiency is associated with
oligospermia, decreased serum testosterone
levels
 Seminal plasma zinc concentrations differ
between fertile and subfertile men. Zinc
levels are lower in infertile men with
diminished sperm count.
 It protects the sperm structure against
free radical.

Zinc
 It is important for DNA structure in
sperm and protects it from breaking
down.
 Zinc is useful to enhance maturation
and motility of spermatozoa as a result
of stabilising effects on biological
membranes.
 Several studies have found
supplemental zinc may prove helpful in
treating male infertility.

 37 patients with idiopathic infertility of
more than five-years duration and
diminished sperm count received 24 mg
elemental zinc from zinc sulfate for 45-50
days.
 In the 22 subjects with initially low
testosterone levels; a significant increase
in testosterone levels and sperm count
(from 8 to 20 million/ml) was noted, along
with nine resulting pregnancies
Zinc
Netter A Arch Androl 1981;7:69-73. Alternative Medicine Review ◆ Volume 5, Number 1 ◆ 2000
december 11 CC VITAMINE E

Lycopene
 Lycopene is a naturally synthesized
carotenoid found in fruits and vegetables
and is an important component of the human
redox defense (antioxidant)mechanism
against free radicals.
 It is found in high concentrations in the
testes and seminal plasma. Levels tend to be
lower in men suffering from infertility.

Lycopene
 It neutralises free radicals produced by
sperm or leucocytes.
 It has potent anti-inﬂammatory
activity, thereby reduces seminal
leucocytes production of free radicals.

Lycopene
 Gupta and Kumar evaluated the effect of
oral lycopene therapy in 30 men with
iOAT.
 A 2000 mcg dose of lycopene, twice a day
for three months, led to
– statistically significant improvements in the sperm concentration
for 66% of patients and motility in 53%.
– Those with baseline sperm concentration less than 5 million/ml
did not exhibit improvement in response; higher baseline
concentrations resulted in six pregnancies in 26 patients.
gupta p international urology and nephrology 2000; 34: 369–372}

Lycopene
 50 patients having IOAT were given
Lycopene 8 mg daily till their sperm
analysis improved to optimal level or
pregnancy was achieved.
 Results:
 36% pregnancy rate with improvement of sperm count and
functional sperm concentration in 70% and 60% respectively,
 sperm motility improved in 54% while 38% showed improvement
in sperm morphology.
Indian J Urol 2001;18:57-61

Vitamin E (α-tocopherol)
• lipid-soluble antioxidant .
• Interrupts the chain reactions involving
lipid peroxidation.
• Confers its protective effects by shielding
sperm membrane components from OS
damage.
• Recent randomized trials have reported
vitamin E to be efficacious in treating
infertility in males with oxidative stress.
• Indian J Urol. 2011 Jan-Mar; 27(1): 74–85.

Vitamin C (ascorbic acid)
• A water-soluble ROS scavenger with high
potency. Found in concentrations 10fold
higher in seminal plasma than in serum.
• Seminal plasma ascorbic acid
concentrations are positively correlated
with percentage of morphologically normal
spermatozoa.
• A randomized study by Rolf et al: vitamin C
and E for 56 days did not improve semen
parameters, or pregnancy rates in iOAT.

Selenium (Se)
• Essential for testicular development,
spermatogenesis, motility & function.
• Protects against oxidative DNA damage in
sperm cells.
• Role of Se is mediated via selenoenzymes,:.
– At least 25 selenoproteins in human,maintain
sperm structure integrity.
– Se deficiency: loss of motility, & increased
incidence of sperm-shape abnormalities, mostly
of the sperm head.

Selenium (Se)
• A recent randomized controlled trial
showed that vitamin E and selenium
improved sperm motility.
• Some studies reported:
» Correlation between Se levels in seminal
plasma & percentage of morphologically
normal sperm.
» Positive correlation levels between sperm
concentration and seminal plasma Se in
infertile patients.

N-acetyl cysteine (NAC)
• A derivative of the naturally occuring amino acid L-
cysteine & has antioxidant properties.
• As precursor of glutathione (GSH), NAC increases
concentration of this endogenous reducing agent &
also directly alleviate OS by scavenging free radicals.
• Antioxidant actions of NAC play an important role in
germ cell survival in human seminiferous tubules in
vitro.

N-acetyl cysteine (NAC)
• A randomized controlled trial by
Safarinejad et al., reported that by the
end of a 26-week treatment with NAC &
selenium,
– significant motility increased in combined
treatment group &in those patients receiving
selenium alone, compared to placebo.
– Combination treatment led to significantly
better sperm parameters than treatment with
only selenium.
J Androl. 2000;21:53–7.

Zinc and folic acid
• Both are essential for transfer RNA &
DNA synthesis.
• In a randomized controlled trial,
– 5 mg folic acid & 66 mg zinc sulfate was
given daily.
– Subfertile men demonstrated a significant
74% increase in total normal sperm count
and a minor increase of 4% in abnormal
spermatozoa. A similar trend was observed
in fertile men.
Fertil Steril. 2002;77:491–8.

RCTs with positive effect of
oral antioxidants on sperm
parameters
Asian Journal of Andrology (2011) 13, 374–381

RCTs with positive effect of
oral antioxidants on sperm
parameters

Micronutrients in management
of male infertilty-Summary
 Use of micronutrients in idiopathic oligo,
astheno and oligoasthenospemia improve
sperm quantity and quality and aid a couple
in achieving pregnancy.
 Plays important role in sperm energy
metabolism, provide primary fuel for sperm
motility.
 Helps sperms to mature
 Prevent lipid peroxidation of sperm
membranes
Contd…

Micronutrients in management
of male infertilty-Summary
 Protects sperm DNA and cell membranes from free
radical induced damage and apoptosis.
 Augment scavenging capacity of seminal
plasma.Improves sperm count, motility and
morphology.
 Carnitine/acetyl-L-carnitine can improve sperm
functions in idiopathic & low-grade varicoceles OATs.

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Physiology of Male Infertility | Seeds of Innocence

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