- 1. How Old is Too Old? Age, Genetics and Reproduction Marcelle
I. Cedars, M.D. Director, Division of Reproductive Endocrinology
UCSF
2. What is Reproductive Aging?
- Quantity:Natural process of oocyte loss
-
- Fourth month of fetal development
-
- Loss acceleration (approx. age 37)
3. 4. What is Reproductive Aging?
- Quality:decreased implantation potential
-
- Increase in meiotic non-disjunction
-
-
- Deficiencies of the granulosa cells
5. Reproductive Aging:Why do we care?
- 20% of women wait until they are at least 35 years of age
before having their first child
-
- Establishment of a career
-
- Awaiting a stable relationship
-
- Desire for financial security
-
- False sense of security provided by high-tech fertility
procedures
6. 7. Normal Biological DeclineGougeon, Maturitas, 30:137-142,
1998 8. Percent Increase in Birthrates CDC Vital and Health
Statistics 2000 1976 1980 1985 1990 1995 35-39 30-34 40+ 15-19
25-29 20-24 9. 10. Concurrent Loss in Quantity AND Quality 11.
Oocyte Quality
12. Abnormalities in oocytes increase with age 13. 14. Impact of
Geneticson Ovarian Aging
-
-
- Familial association with age at menopause
-
-
- 30-85% estimates of heritability
-
-
- Alterations in blood flow
-
-
- Toxins in the environment
15. 16. Reproductive Aging Lifestyle Factors
-
-
- Affect the follicular microenvironment
-
-
- Affect hormonal levels of the luteal phase
-
-
- Accelerates oocyte loss (menopause 1-4 years earlier)
-
-
- Negative affect on sperm production, motility and
morphology
-
-
- Increased risk for DNA damage
17. Reproductive Aging Lifestyle Factors
-
-
- Alterations in hormonal profile and anovulation
-
-
- Increased time to conception
-
-
- Increased time to conception
18. Reproductive Aging Lifestyle Factors
-
- Some reduction with ART outcome noted
-
- Studies with problems of recall bias
-
- Suggestion of association with reduced fertility
-
- Studies with problems of recall bias
19. Reproductive Aging Lifestyle Factors
20. Loss of Ooctye Quality
- Abnormal fertilization, arrest of early development
- Post-implantation problems
-
- developmentally delayed child (down syndrome)
21. Assessing Reproductive Age
22. Assessing Reproductive Age
-
- Anti-mullerian Hormone (AMH)
23. Reproductive Aging Is it Quantity or Quality
-
- Indirect measure of follicular pool
-
-
- Decrease in inhibin B leads to increase FSH
-
- Not associated with increased risk of aneuploidy (vanMongfrans,
2004)
-
- Decreased predictive ability in populations with a low
prevalence (young women)
24.