Truths & Myths about Diet In Fertility and Gender Selection

1. Truths & Myths about Diet In Fertility and Gender Selection Dr. Eeson Sinthamoney Consultant Obstetrician and Gynaecologist Hospital Kuala Lumpur

2. Outline • Weight and fertility • Nutrients and fertility • Gender selection

3. Weight and fertility • In women: raised BMI associated with difficulty in conceiving • Overweight and obese women undergoing fertility treatment had significantly lower pregnancy rates and higher miscarriage rates • Underweight women had less embryos available

4. Weight and fertility • In men, relationship less clear • Many studies indicate high or low BMI associated with significantly reduced sperm quality • However some evidence also suggests otherwise • Body weight loss may be reasonable in male infertility

5. Nutrients and fertility - truth or myth? • Many studies demonstrate the positive effects of OTC supplementation on female fertility, semen parameters and pregnancy outcomes • Conversely, also many studies that demonstrate lack of improvement • Gold standard of evidence?

6. Nutrients and fertility Why is good evidence difficult to find? • Infertility often multifactorial • Baseline dietary intake • Single agent versus multiple supplements • Dosages?

7. Nutrients and fertility in women • Several small studies suggest that some nutrients may be essential in female reproduction • Current interest focused on vitamin D and anti-oxidants

8. Nutrients and oxidative stress Cell respirationl Production Alcohol / tobacco smoke / environmental pollutants Reactive oxygen species Scavenging, disposing or suppresing Anti-oxidant co-factors Example: selenium, zinc and copper Anti-oxidants (example Vitamin C and E)

9. Which are anti-oxidants? • Main nutrients: vitamin C, vitamin E, selenium, and the carotenoids (vitamin A precursor) • A multitude of other nutrients, including minerals such as copper, manganese, zinc, flavonoids (such as grape seed extract and phenols found in green tea) • Co-enzyme Q10, also possess antioxidant properties

10. Impact of oxidative stress on female fertility • Evidence exists supporting the role of oxidative stress in male fertility • However, in women, while there is suggestion of the same, relationship not well addressed

11. Anti-oxidants and female fertility

12. Nutrients and fertility in women- Vitamin D • Involved in female reproduction and improves fertility treatment outcome • Some studies show that women with higher serum and FF vitamin D levels have higher pregnancy rates after IVF Replete vitamin D stores predict reproductive success following in vitro fertilization. Ozkan S et al. FertilSteril. 2010 Sep;94(4):1314-9. Vitamin D and fertility-a systematic review. Lerchbaum E, Obermayer-Pietsch BR. Eur J Endocrinol. 2012 Jan 24.

13. Oxidative stress and infertility in women - summary • Some strong but indirect evidence that oxidative stress affects fertility • Best available evidence suggests a varied diet with regular use of multivitamins, limited caffeine and alcohol and a healthy body weight promotes fertility

14. Nutrients and fertility in men • Up to 50% of fertility problems involve a male factor • More information available concerning nutrients and sperm characteristics

15. Carnitines • Assist sperm metabolism as an energy source for spermatozoa and effect motility and sperm maturation • Also an anti-oxidant • Multiple RCT studies demonstrate improvements in concentration, motility, morphology also the converse also shown • Primarily meat products • Dosage?  Up to 3g/day safe

16. Co-enzyme Q-10 • Studies in infertile men demonstrate positive co-relation between higher seminal fluid CoQ10 concentrations and sperm motility and fertilization potential in couples undergoing IVF  pregnancy rates? • Source: oily fish (sardines), organ meat, whole grain, vegetables • Dosage: 200-300mg/day up to 12mg/kg/day

17. Folic acid • Important role in DNA synthesis and proper cell function • Critical role in spermatogenesis • Mixed reports on effect of folate on male fertility • Sources: dark green leafy veg, beans, eggs, meats • Unsure if additional folate above RDA will improve fertility

18. Glutathione • One of the most abundant anti-oxidant produced in the body • Important role in maintaining exogenous anti-oxidants (Vitamin C, E) in its active form • Shown to improve sperm motility, improved sperm concentration and decreased sperm DNA fragmentation • Source: fresh meat, fruits & veg • Up to 3g/day tolerated • Poor oral availability  IM administration

19. Vitamin A • B-carotene is pre-cursor or vitamin A • Anti-oxidant properties • Specific benefits on sperm production and function difficult to clearly demonstrate • Up to <10000iu/day tolerated • However, readily stored and may reach toxic levels

20. Vitamin C • Associated with various improvements in semen quality • Supplementation up to 1000mg/day improves count, motility, viability and morphology • Protects sperm DNA against oxidative damage • May work synergistically with other vitamins and anti-oxidants • RDA: 90mg/day; dosage: 500mg/day

21. Vitamin E • Potent anti-oxidant • Substantial support for improvement in many sperm parameters • Sources: veg oil, meat, poultry • Recommended dose: 200-400iu/day • Upper daily intake: 1600iu/day • May be increased risk of complications (CVS) if >400iu/day and bleeding risk >800iu/day

22. Selenium • Role in maintaining normal testicular development, spermatogenesis and sperm function • Studies support use of selenium to improve sperm motility, concentration and morphology especially I combination with vitamin E • Optimal dosing: 100-210mcg/day • Sources: meat, seafood, eggs; veg is poor source

23. Zinc • Vital role in testicular steroidogenesis, testicular development, sperm O2 consumption and other functions • Chronic mild zinc deficiency assoc with oligospermia, decreased serum T2 • Zn therapy associated with improvement in sperm motility, reduced sperm DNA fragmentation and other improvements • Upper limit: 40mg/day

24. Gender selection Not new! • mother-in-law’s advice • Nutrients? • Sperm sorting mechanisms – varied options, evolving over time post sort purity average 87.9% 4. PGD Flow cytometric sorting of human sperm: MicroSort clinical trial update. Karabinus DS. Theriogenology. 2009 Jan 1;71(1):74-79

25. Conclusion • Lack of good quality evidence • However: information available suggests that selective use of certain supplements beneficial but dosage information lacks clarity • Certainly- anti-oxidant use may improve live birth and pregnancy rate outcomes for subfertile couples undergoing ART • However: avoid doses beyond RDA to avoid complications • Blood level assessment?

26. Thank you