1. Martin Imhof
Landesklinikum Korneuburg/Vienna
Mikronährstoffe und ihr
therapeutischer Effekt auf genetische
Aberrationen und DNA am Beispiel
der Spermienqualität“
Menopause, Andropause und Antiaging. Wien Hotel Hilton 2012

2. Semen quality and
Sperm DNA damage
in relation to urinary
bisphenol A .
Bisphenol A
John D. Meekera et al. Reproductive Toxicology 2010

3. 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

4. Ungeklärte Fertilitätsstörungen?

5. 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 …………

6. 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 …..

7. 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.

8. DNA Fragmentation
einer oder mehrere Brüche
einer oder beider Stränge der
Doppelhelix

9. 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

10. 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

11. Gibt es einen Mangel an Mikronährstoffen?
Guidelines on food fortification
with micronutrients
Lindsay Allen et al.
World Health Organization
2006
Male factor subfertility: possible causes and the
Impact of nutritional factors.
Wong WY et al.
Fertil Steril 2000 73:435-442

12. Gibt es einen Mangel an Mikronährstoffen?

13. Gibt es einen Mangel an Mikronährstoffen?

14. 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

15. 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“

16. 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

18. 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

19. THERAPY COMPARED TO CONTROL

20. 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

21. 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….

22. 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

23. 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

24. Inclusion – criteria
Infertility for > 1 years
2 pathological spermiograms
Informed consent
Exclusion - criteria
Varicosis
Infection
Aspermia
Hormonal disorder
CONTROLLED STUDY – STUDY SETTING

27. Kontrolle
Keine 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).

28. 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 ….

29. DNA Fragmentation
sperm chromatin structure analysis
< 15% normal
15-30% IUI necessary
> 30% ICSI necessary

30. 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

31. Vielen Dank für Ihre
Aufmerksamkeit