Imhof MartinGeneral Public Teaching Hospital Korneuburg/Vienna

Micronutritients and

Male Subfertility

9th International iCSi Conference: Budapest 2008

replacement level and very low fertility

Developement of Sperm Quality

Swan et. al. – National Institute of environmental health sciences

•Review of 61 published studies•Data collected over 52 years (1938 to 1990)•Decline in average sperm density in U.S. and other Western countries

Average annual decrease of

U.S. 1.5 mio/ml = minus 1.5%/year

Europa minus 3.1%/year

DECREASE IN SPERM QUALITY

Semen quality and sperm DNA damagein relation to urinary bisphenol A among men from an infertility clinic.

Bisphenol A

John D. Meekera et al. Reproductive Toxicology 2010

Decline of Fertility

Environmental hormones

Oxidative stress

Change of life style

Change in nutrition habits

Lack of micronutritients

LACK OF MICRONUTRITIENS IN FOOD

MALE SUBFERTILITY AND NUTRITION

MALE SUBFERTILITY AND NUTRITION

Reduction of Sperm Quality

• No Disease?

• Defiency Syndrom?

Could therapy be Supplementation ?

LACK OF MICRONUTRITIENS IN FOOD

Guidelines on food fortification with micronutrientsLindsay Allen et al. World Health Organization2006

Male factor subfertility: possible causes and theImpact of nutritional factors. Wong WY et al. Fertil Steril 2000 73:435-442

DECREASE IN SPERM QUALITY

Dietary intake of antioxidant nutrients is associated with

semen quality in young university students

Mínguez-Alarcón, Hum Reprod. 2012 Sep;27(9):2807-14

In this cross-sectional study, 215 young men

Our study suggests that some sperm parameters are sensitive

to dietary intake of antioxidant nutrients

EFFECT OF MICRONUTRITIENTS

Cochrane Database Syst Rev. 2011 Jan 19;1:CD007411.

Antioxidants for male subfertility.

Showell et al.

AUTHORS' 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….

SPERMIOGENESIS

Day 1 Day 18 Day 36 Day 54 Day 72

Spermiogenesis

2x1 Capsule daily for 3 Month

L-Carnitin 440 mg L-Arginine 250mg Vitamin E 120 mg Folic-acid 800 μg Zinc 40 mg Selenium 60 μg Glutathione 80 mg Coenzyme Q10 15 mg

Study Medication „PROFERTIL“

EFFECTS ON SPERMIOGENESIS

Hormonal Regulation

Morphology/Density

Energy/Motility

Enzym/Capazitation

L-Carnitin 440 mg

L-Arginine 250 mg

Vitamin E 120 mg

Folic-acid 800 ug

Zinc 40 mg

Selenium 60 ug

Glutathione 80 mg

Coenyme Q 10 15 mg

Inclusion – criteria

Infertility for > 1 years 2 pathological spermiograms Informed consent

Exclusion - criteria

VaricosisInfectionAspermiaHormonal disorder

CONTROLLED STUDY – STUDY SETTING

Therapy Group 132 men, age Ø 34 a (18-43)

2 Capsules/day MICRONUTRITIENTS (PROFERTIL) for 3 month

Control Group 73 men, age Ø 38 a (22-52)

No TREATMENT / CHANGE OF LIFE STYLE

CONTROLLED STUDY – STUDY SETTING

2 path spermiogr.

Questionare Questionare

Treatment group Profertil 2 capsules

Control groupChange life style

Observation period

Telephone Follow up

End of study

12 monthInclusion

3 monthStudy period

6 monthFollow up

RESULTS OVERALL

Tot. Motility

47%

32%

20 %

10 %

50 %

40 %

30 %

RESULTS THERAPY GROUP

Prog. Motility

49%

30,5%

0 %

25 %

+83,1%

+36,4%

THERAPY COMPARED TO CONTROL

After 3 month treatment

Study Group Control Group

132 74

34 preg.(25,8%) 11 preg.(14,8%)

Improvement with Micronutritients after 3 Month

DNA Fragmentation

sperm chromatin structure analysis

< 15% normal 15-30% IUI necessary> 30% ICSI necessary

EFFECT OF MICRONUTRITIENTS

Cochrane Database Syst Rev. 2011 Jan 19;1:CD007411.

Antioxidants for male subfertility.

Showell et al.

AUTHORS' 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….

Oxidative DNA damage impairs global sperm DNA

methylation in infertile men.

Tunc O, J Assist Reprod Genet. 2009 Sep-Oct;26(9-10)

CONCLUSIONS:

..... while antioxidant supplementation appears to have the

potential to reduce DNA damage and normalize sperm

DNA methylation.

EFFECT OF MICRONUTRITIENTS

Antioxidants and sperm DNA damage: a clinical

perspective.

Zini A, J Assist Reprod Genet. 2009 Aug;26(8):427-32.

RESULTS: . the data suggest that dietary antioxidants may

be beneficial in reducing sperm DNA damage, particularly,

in men with high levels of DNA fragmentation ...

EFFECT OF MICRONUTRITIENTS

Schuetz a, H. Kurz a, M. Imhof b

67 sub-fertile males (active treatment group)

40 Sub-fertile men receiving no active treatment served as controls

Main outcome measure was change in sperm-hyaluronan binding assay indicating DNA fragmentation index after 3 months.

SPERM DNA FRAGMENTATION INDEX DECREASES AFTER

MICRONUTRIENT SUPPLEMENTATION

Micronutrients intake is associated with improved sperm DNA quality in older men.

Schmid et al Fertil Steril 2012 Aug 23.

PATIENT(S): 22-80-year-old nonsmoking men (n = 80)

CONCLUSION(S): Men with higher dietary and supplement intake of certain micronutrients may produce sperm with less

DNA damage, especially among older men.

DNA EFFECT OF MICRONUTRITIENTS

CONCLUSION

Sperm quality and male fertility is decreasing

Medical treatment of sperm quality unsuccessful

Decline of sperm quality may be a defiency syndrome not a disease

CONCLUSION

Micronutritients are lacking in western countries

Change of life style may improve sperm quality

Micronutritients improve sperm quality in literature

Controlled prospective study prooves significant improvement compared to control group

Micronutritients improve DNA sperm quality