micronutrients in male infertility by dr shashwat jani

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

Dr Shashwat Jani +91 99099 44160.

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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


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.’


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


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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Male Infertility


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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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L - Carnitine


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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


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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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Co Enzyme Q 10


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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


• 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


• 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



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Lycopene


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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


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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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10

2030

4050

6070

Imp

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vem

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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


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



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Zinc


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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.


Effects of zinc supplementation on subfertility


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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


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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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FOLATE


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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


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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]

METHYL COBALAMINE


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• 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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Vit - E


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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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5-Dec-16 60Dr Shashwat Jani +91 99099 44160.

micronutrients in male infertility by dr shashwat jani

Health & Medicine