Martin ImhofLandesklinikum Korneuburg/Vienna

Mikronährstoffe und ihr therapeutischer Effekt auf genetischeAberrationen und DNA am Beispiel

der Spermienqualität“

Menopause, Andropause und Antiaging. Wien Hotel Hilton 2012

Semen quality and Sperm DNA damagein relation to urinary bisphenol A .

Bisphenol A

John D. Meekera et al. Reproductive Toxicology 2010

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

•Review of 61 published studies•Data collected over 58 years (1938 to 1996)•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

Rückgang der Spermienqualität

Ungeklärte Fertilitätsstörungen?

Effekte der DNA Fragmentation

Fertil Steril. 2002 Aug;78(2):313-8.

Saleh ED; Increased sperm nuclear DNA damage in normozoospermic infertile men: a prospective study.,

CONCLUSION(S): ….. a significant increase in DNA damage can be found in sperm from infertile men with normal standard sperm parameters …………

Effekte der DNA Fragmentation

PLoS One. 2012;7(9):e44679

Ribas-Maynou J, Double stranded sperm DNA breaks, measured by Comet assay, are associated with unexplained recurrent miscarriage in couples without a female factor.

Conclusion: ….. sperm DNA breaks are related to the paternal risk of having recurrent pregnancy loss …..

Effekte der DNA Fragmentation

Fertil Steril. 2007 May;87(5):1077-86.

Sloter ED Frequency of human sperm carrying structural aberrations of chromosome 1 increases with advancing age.

CONCLUSIONS: Our findings suggest that advancing male age is associated with a gradual and significant increase in the risk of fathering children with various chromosomal defects such as segmental aneusomy syndromes.

DNA Fragmentation

einer oder mehrere Brüche einer oder beider Stränge der Doppelhelix

Effekt der DNA Fragmentation

Spermien haben kein eigenes DNA-Reparatursystem, Schäden können im Gegensatz zur Oozyte nicht repariert werden

DNA-Fragmentation von Samenzellen im kaudalen Nebenhoden und im Ejakulat am höchsten da höchste Radikalbelastung (ROS)

DNA Fragmentation bewirkt Störung der Kapazitation und Abbruch in der Frühentwicklungsphase des Embryos

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

Zini A, Antioxidants and sperm DNA damage: a clinical

perspective.

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 on DNA

Gibt es einen Mangel an Mikronährstoffen?

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

Gibt es einen Mangel an Mikronährstoffen?

Gibt es einen Mangel an Mikronährstoffen?

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

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“

EFFEKTE auf die SPERMIOGENESE

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

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

THERAPY COMPARED TO CONTROL

6 month after end of therapy

Study Group Control Group

132 74

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

Improvement with Micronutritients after 3 Month

Mikronährstoffe und DNA Fragmentation

Cochrane Database Syst Rev. 2011 Jan 19

Showell et al., Antioxidants for male subfertility.

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….

Assist Reprod Genet. 2009 Sep-Oct;26(9-10)

Tunc O, J Oxidative DNA damage impairs global

sperm DNA methylation in infertile men.

CONCLUSIONS: ..... while antioxidant supplementation

appears to have the potential to reduce DNA damage and

normalize sperm DNA methylation.

EFFECT OF MICRONUTRITIENTS on DNA

Therapy Group 67 men, age Ø 39 a (24-48)

2 Capsules/day MICRONUTRITIENTS (PROFERTIL) for 3 month

Control Group 40 men, age Ø 37 a (26 – 50)

No active TREATMENT

Main outcome measure was change in sperm-hyaluronan

binding assay indicating DNA fragmentation after 3 months.

SPERM DNA FRAGMENTATION INDEX DECREASES AFTER MICRONUTRIENT SUPPLEMENTATION

Inclusion – criteria

Infertility for > 1 years 2 pathological spermiograms Informed consent

Exclusion - criteria

VaricosisInfectionAspermiaHormonal disorder

CONTROLLED STUDY – STUDY SETTING

KontrolleKeine Therapie

20 %

40 %

100 %

80 %

60 %

Ergebnisse

Therapie Micronährstoffen Profertil

0 %

56%

69%

20 %

40 %

100 %

80 %

60 %

0 %

74%

64%

(p<0.05) (p=0.083).

EFFECT OF MICRONUTRITIENTS on DNA

Reprod Biomed Online. 2009;19 Suppl 3:35-43.

Tarozzi N Sperm-hyaluronan-binding assay: clinical value in conventional IVF under Italian law.

…. The results underline the ability of hyaluronan to select spermatozoa with higher DNA integrity and morphology ….

DNA Fragmentation

sperm chromatin structure analysis

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

Zusammenfassung

Oxidative Prozesse verursachen Fertilitätsstörungen

Freie Radikale führen zu Brüchen in der Spermien DNA

Mikronährstoffe können als Radikalfänger auftreten

Mikronährstoffe verringern die DNA Fragmentationsrate und erhöhen die Hyluronsäurebindung

Mikronährstoffe beeinflussen positiv die Schwangerschaftsrate und den Schwangerschaftsverlauf

Vielen Dank für Ihre Aufmerksamkeit