micronutrients in male infertility by dr shashwat jani
TRANSCRIPT
Dr. Shashwat Jani.M. S. ( Obs – Gyn )
Diploma in Advance Laparoscopy.
Consultant Assistant Professor,
Smt. N.H.L. Municipal Medical College.
Sheth V. S. General Hospital , Ahmedabad.
Mobile : +91 99099 44160.
E-mail : [email protected]
Many studies and researches have proved that there is a strong positive relationship between Micronutrients & Male fertility.
5-Dec-16Dr Shashwat Jani +91 99099 44160.
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In order to examine the association between micronutrients and infertility, articles with case-control, descriptive, cohort, and interventional (clinical trials) design, published between 1984 and 2014, were accessed through PubMed and Embase databases, using keywords such as “micronutrients “ , "oxidative stress", "antioxidant", "vitamins", "minerals", and "infertility“….5-Dec-16
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Infertility affects about 15 – 20 % of married couples half of which attributed to male infertility.
Defective sperm function considered to be most common cause of male infertility.
Apart from all the conventional causes of male infertility , a new & important cause has been identified as being responsible for
Idiopathic male infertility :
Reactive Oxygen Species ( ROS ).
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Causes for Male Infertility
31.7
16.6
9
8.9
8.5
5.8
5
4.2
2.3
1.5
6.5
0 5 10 15 20 25 30 35
Idiopathic
Varicocele
Infection
Hypogonadism
Cryptorchidism
Malformation
Systemic
Immunologic
Tumor
Obstruction
Other
Hum Reprod Update 1999; 5(2): 120Percent (%)65-Dec-16
Dr Shashwat Jani +91 99099 44160.
Idiopathic male Subfertility
40-75% of cases.
Most common pathological cause of Idiopathic Subfertility is –
‘ free radical induced damage to the sperm. ‘
Free radical is defined as…
‘ Oxygen molecule containing one or more unpaired electrons in atomic or molecular orbitals.’
75-Dec-16Dr Shashwat Jani +91 99099 44160.
R.O.S.
• In a healthy man, a delicate balance exists between physiological ROS & Antioxidants in the male reproductive tract.
• High level of seminal ROS have been found in 30 – 80 % of infertile men.
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Biology of ROS
Pathology stems from imbalance between production and scavenging
Production Degradation
95-Dec-16Dr Shashwat Jani +91 99099 44160.
Reactive Oxygen Species in Male Infertility
I. ROS generation in semen
: About 40% in infertile men (Iwasaki & Gagnon, 1992)
II. Harmful action mechanism of ROS on sperm
by overwhelming endogenous antioxidant defenses
1. Cause sperm membrane lipid peroxidation
2. Decrease membrane fluidity
3. Reduce sperm motility
4. Decrease sperm-oocyte fusion capability
5. Impair fertilizing capacity5-Dec-16
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ROS and Male Infertility
Reactive Oxygen Species is
one of the major
contributors to male
Infertility & cause Damage to the sperm
• Cell membrane
• DNA molecules
• Lipids
• Proteins
Urology. 1996;48(6):835–850.
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Genetic Causes
DNA damage and mutations in mitochondrial DNA have
been linked to poor sperm motility and male subfertility.
A genetic factor located at Yq11 has been established to be
important for male germ cell development and Yq11 damage
may lead to male infertility.
Deletions of AZFa, AZFb and AZFc (Microdeletions in the Y-
chromosome) can result in male infertility.
Klinefelter’s syndrome, Kallman’s syndrome can also
result in male infertility
Indian J Med Res. 2008;127:124-132.
J. Biosci. 2001;26(4):492-435.5-Dec-16Dr Shashwat Jani +91 99099 44160.
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Environmental Causes
The factors are as follows:
• Infection
• Excessive heat
• Radiation exposure
• Heavy metal toxicity
• Cigarette smoking
• Xeno-estrogen exposure
• Pesticides and other chemicals Altern Med Rev. 2000;5(1):28-38.
Human Reproduction, 2001;16(8):1768-1776.
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http://www.gfmer.ch/Endo/Fellows_11/Pdf/Infertility_environment.pdf
Human Reproduction, 2001;16(8):1768-1776.
Occupationally Free time
Physical activity Prolonged sitting
Thermoregulation of scrotum
elevation of scrotal temperature
HEAT EXPOSURE
Spermatogenesis
Quality and quantity of sperm production
(count, morphology, motility, delayed coception)
Sedentary lifestyle
Environmental Causes
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1) Poor sperm motility
2) Teratozoospermia
3) high number of round cells in semen
4) increased semen viscosity
5) poor sperm membrane integrity on hypo osmoler swelling test
6) Poor fertilization on routine IVF.
7) Poor sperm motility after overnight oocyte incubation
8) poor blastocyst development in absence of a clear female factor.
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Nutritional Considerations
• Various micronutrients are
associated with male fertility.
• Deficiency of these
micronutrients may result in
infertility.
Nutritional Factors
Free radical scavengers
L-Carnitine Lycopene
Coenzyme Q10
Vitamin C
Zinc Vitamin E
Arginine Glutathione
Vitamin B12
Selenium
Altern Med Rev. 2000;5(1):28-38.
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Nutrition plays vital role in maintaining male fertility:
Involved in the successful maturation of sperm
Provides nutrition for motility of sperm
Improvement in sperm count and motility
Helps in production of sex hormones
Prevents sperm damage
Reduction in sperm DNA fragmentation
Suppression of ROS productionAltern Med Rev. 2000;5(1):28-38.5-Dec-16
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Three compartments of the male genital tract :
• Epididymal tissue,
• Seminal plasma, and
• Spermatozoa
Maintain the highest free L-carnitineconcentrations in the body.
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The main function of L-Carnitine in the epididymis is to provide an energetic substrate for spermatozoa.
May be involved in the successful maturation of sperm.
L-Carnitine is necessary for transport of fatty acids into the mitochondria to produce energy.
Low levels of L-Carnitine reduces fatty acid concentrations within the mitochondria, leading to decreased sperm motility
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L-Carnitine: Clinical Trials
According to a study conducted by Costa et al. L-carnitine
increased the sperm parameters drastically
10.8
28.4
3.73.1
142.4
18
32.5
4.1
20.3
163.3
0
20
40
60
80
100
120
140
160
180
Baseline At 4 months
Motile spermatozoa (%)
Mean velocity (microns)
Linearity index
Spermatozoa with rapidlinear progression (%)
Number of ejaculatedspermatozoa
Andrologia.1994;26:155-159.5-Dec-16
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L- Carnitine for asthenospermia with varicocele
Carnitine
Placebo
Zhonghua Nan Ke Xue. 2004;10(9):671–672.
There was significant improvement in sperm count,motility and pregnancy rates in infertility due to varicocele.5-Dec-16
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L- Carnitine in idiopathic asthenozoospermia: a multicenter study.
Italian Study Group on Carnitine and Male Infertility.
Andrologia 1994;26:155-159
N = 100 patients
L-carnitine - 3 g/day
Duration - 4 months.
Percentage of motile spermatozoa increased from 26.9 ± 1.1 to 37.7 ± 1.1 %.
Total number of spermatozoa per ejaculate also increased
Conclusion - Oral administration of L-Carnitine improves sperm quality
5-Dec-16Dr Shashwat Jani +91 99099 44160.
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• Mazzilli et al, established strict correlation between intrasperm L-carnitine content and sperm motility survival in bovine cervical mucus. This is possibly due to the fact that lipids are an important energy source for sperm in cervical mucus and to metabolize these lipids intrasperm Lcarnitine is essential.
• L-carnitine not only helps in lipid metabolism but also it modulates the reserves of free CoA, essential for tricarboxylic acid ( TCA ) cycle regulation.
• Therefore, L carnitine content can be considered as an indicator of sperm motility life span in cervical mucus.
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Anti Oxidant Property
It is also proposed that carnitine exerts antioxidant properties as a result of repairing mechanism by which elevated intracellular toxic acetyl-CoA is removed and fatty acids in membrane phospholipids are replaced.
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• In sperm cells, coenzyme Q10 (CoQ10) is concentrated in
the mitochondria.
• Coenzyme Q10 is responsible for energy for
movement and all other energy-dependent processes in the
sperm cell.
• Reduction in levels of CoQ10 is observed in sperm cells
and seminal plasma of idiopathic (IDA) and varicocele-
associated (VARA) asthenozoospermic patients.*
• It is observed that sperm cells, characterized by low
motility and abnormal morphology, have low levels of CoQ10.
*Andrologia 34 (2002), 107–111.
Co enzyme Q10 - Mechanism
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• Administration of CoQ10 increased the pregnancy rateby 36% and with improvement of sperm countand functional spermconcentration in 70% and 60% individuals, respectively.
• Sperm motility and sperm motility index improved in 54% and 46 % while 38 % showed improvement in sperm morphology.
Folia Med (Plovdiv).2005;47(1):26–30.
Coenzyme Q10: Clinical Trials
Improvement in sperm motility, motility
Index and sperm morphology
Sperm
MorphologyMotility
index
Sperm
Motility
345-Dec-16Dr Shashwat Jani +91 99099 44160.
• Patients – 22 infertile men with idiopathic asthenozoospermia.
• Coenzyme Q10 - 100 mg for 6 months
• A significant increase was also found in sperm cell motility
Conclusion:
• The exogenous administration of CoQ(10) may play a positive role in the treatment of asthenozoospermia.
• This is probably the result of its role in mitochondrial bioenergetics and its antioxidant properties.
Fertil Steril. 2004 Jan;81(1):93-8.
Coenzyme Q10: Clinical Trials
355-Dec-16Dr Shashwat Jani +91 99099 44160.
Lycopene is a bright red pigment and phytochemical found in tomatoes and other red fruits, water melon & guava.
Belongs to a class referred to as carotenoids which are yellow, orange, and red pigments synthesized by plants .
Lycopene
385-Dec-16Dr Shashwat Jani +91 99099 44160.
The general mechanism by which Lycopene works is by preventing oxidative damage to sperms, which includes
• Damage to the cell membrane
• DNA molecules
• Lipids
• Proteins
Lycopene has been demonstrated to be the most potent antioxidant with the ranking: lycopene > α-tocopherol > α -carotene > β- carotene > lutein.
Lycopene – Biological activity
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Lycopene: Clinical Trials
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5346
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2030
4050
6070
Imp
ro
vem
en
t
(%)
Sperm
concentr
ation
Motility
Morp
holo
gy
Lycopene in infertility
Int Urol Nephrol. 2002;34:369–372.
A Study evaluated the effect of oral lycopene therapy in men with idiopathic Subfertility.
Lycopene - 2000 mcg, twice a day for three months
N - 30 Patients
405-Dec-16Dr Shashwat Jani +91 99099 44160.
Results : Improvement in sperm concentration - 20 patients (66%)
Improved motility – 16 patients (53%)
Improvement in sperm morphology - 14 patients (46%)
Associated with significant improvement and resulted in six pregnancies in 26 patients (23%)
Conclusion - Lycopene therapy seems to
have a role in the management of idiopathic male Subfertility 415-Dec-16
Dr Shashwat Jani +91 99099 44160.
Zinc is a micronutrient abundantly present in meat and
seafood and serves as a cofactor for more than 80 enzymes
involved in DNA multiplication and protein synthesis
Zinc deficiency is associated with decreased
testosterone levels & sperm count.
Zinc levels are generally lower in infertile men with
diminished sperm count.
Furthermore, zinc finger proteins are implicated in the
genetic expression of steroid hormone receptors*, and zinc also
has anti-apoptotic ** and antioxidant properties.***
*Endocr Rev 1992 :13,129–145. **Curr Drug Targets 2003:4,323–338. ***Free Radic Biol Med 31,266–274.
Rev Prat. 1993;43:146-151.
Ann Nutr Metab. 1986;30:213-218.
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Zinc – Clinical Trials
N - 100 men with asthenozoospermia
Two groups--250 mg twice daily zinc therapy for 3 months and no therapy.
Duration – 6 months
There was significant improvement in the sperm quality; sperm count, progressive motility, fertilizing capacity
Conclusion: Zinc therapy has a role in improving sperm parameters in men with asthenozoospermia
Eur J Obstet Gynecol Reprod Biol. 1998 Aug;79(2):179-84.
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Arginine is essential for sperm motility, metabolism, capacitation, acrosome reaction, and is a precursor for producing petruscine, spermine, and spermidine.
According to a study by Schachter et al. Arginine
significant improved sperm count and motility after
taking 4 g/day for three months.
A recent study conducted in Italia also showed that
arginine is effective in male infertility
The recommended daily allowance (RDA) is 20 g,
with an upper limit of 30 g.
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Adequate folic acid intake is associated with a decreased frequency of sperm DNA abnormalities.
Still its role is controversial.
The RDA is 400 mg.
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Selenium and glutathione are essential to the
formation of phospholipid hydro peroxide
glutathione peroxidase.
Deficiencies of selenium can lead to instability of the
mid-piece, resulting in defective motility
However, it can be toxic if consumed in excess.
ArchAndrol. 1992;29:65-68. Science 1999;285:1393-1396.Environ Mol Mutagen. 2009 [Epub ahead of print]
• Vitamin B12 is important in cellular replication,
especially for the synthesis of RNA and DNA, and
deficiency states have been associated with
decreased sperm count and motility.
• Various studies have shown that Methylcobalamine
improves the sperm parameters
• However, studies show that Methylcobalamine is
effective in only just over 20% of infertile men.
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• Oral supplementation with vitamin E significantly
decreases the malondialdehyde concentration
and improves the sperm motility
• Although Invitro studies have prooved the
efficacy of vitamin E, human studies are lacking
• Although there are few human studies, they
recruited only few patients.
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To conclude Infertile couples are likely to try multiple
Micronutrients hoping to improve their chances of conception with minimal risk and cost before proceeding with ART.
A recent Cochrane review in 2011 did demonstrate improved pregnancy and live birth rates with adequate dosages of Micronutrients.
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