presentation marcelle
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- 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
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- Fourth month of fetal development
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- 6-7 million
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- Birth
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- 1-2 million
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- Menarche
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- 400,000
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- Loss acceleration (approx. age 37)
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- 25,000
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- Menopause
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- 1000
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- Process:Apoptosis
3. 4. What is Reproductive Aging?
- Quality:decreased implantation potential
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- Increase in meiotic non-disjunction
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- Production-line theory
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- Accumulated damage
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- Deficiencies of the granulosa cells
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5. Reproductive Aging:Why do we care?
- Changing Demographics
- 20% of women wait until they are at least 35 years of age before having their first child
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- Establishment of a career
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- Awaiting a stable relationship
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- Desire for financial security
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- 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
- Chromosomes and DNA
- Mitochondria and ooplasm
12. Abnormalities in oocytes increase with age 13. 14. Impact of Geneticson Ovarian Aging
- Complex Trait
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- Genetic
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- Familial association with age at menopause
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- 30-85% estimates of heritability
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- Environmental
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- Oxidative stress
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- Alterations in blood flow
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- Toxins in the environment
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15. 16. Reproductive Aging Lifestyle Factors
- Cigarette smoking
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- Female
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- Affect the follicular microenvironment
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- Affect hormonal levels of the luteal phase
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- Accelerates oocyte loss (menopause 1-4 years earlier)
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- Male
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- Negative affect on sperm production, motility and morphology
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- Increased risk for DNA damage
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17. Reproductive Aging Lifestyle Factors
- Weight:BMI < 20 or > 25
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- Female
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- Alterations in hormonal profile and anovulation
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- Increased time to conception
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- Male
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- Increased time to conception
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18. Reproductive Aging Lifestyle Factors
- Stress
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- Lack of clear evidence
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- Difficult to measure
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- Some reduction with ART outcome noted
- Caffeine
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- Studies with problems of recall bias
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- Suggestion of association with reduced fertility
- Alcohol
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- Studies with problems of recall bias
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- Biological plausibility
19. Reproductive Aging Lifestyle Factors
- Environmental Factors
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- Organic solvents
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- Pesticides
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- Phthalates
20. Loss of Ooctye Quality
- Abnormal fertilization, arrest of early development
- Failure to implant
- Post-implantation problems
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- recognized loss
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- developmentally delayed child (down syndrome)
21. Assessing Reproductive Age
- What are you measuring?
- And Why?
- Reproductive performance
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- Response to stimulation
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- Live-born
22. Assessing Reproductive Age
- Direct measures
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- AFC/ovarian volume
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- Anti-mullerian Hormone (AMH)
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- Inhibin B
- Indirect measures
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- FSH
23. Reproductive Aging Is it Quantity or Quality
- FSH
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- Indirect measure of follicular pool
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- Decrease in inhibin B leads to increase FSH
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- Not associated with increased risk of aneuploidy (vanMongfrans, 2004)
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- Decreased predictive ability in populations with a low prevalence (young women)
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- Antral follicle count
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- Cycle day
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- Follicle size
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