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AGING AND REPRODUCTION

AGING AND REPRODUCTION. REFERENCES. Infertility, 2 nd ed 1997 : Machelle M.Seibel Human Reprod Update 1996;2:459-460 Maturitus 1998;30:103-4 Maturitus 1998;30:105-11 Maturitus 1998;30:113-18 Maturitus 1998;30:127-36 Maturitus 1998;30:137-42.

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AGING AND REPRODUCTION

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  1. AGING AND REPRODUCTION

  2. REFERENCES • Infertility, 2nd ed 1997 : Machelle M.Seibel • Human Reprod Update 1996;2:459-460 • Maturitus 1998;30:103-4 • Maturitus 1998;30:105-11 • Maturitus 1998;30:113-18 • Maturitus 1998;30:127-36 • Maturitus 1998;30:137-42

  3. Causes of the age-related decrease in reproductive potential • Intrinsic aging • Weatheringฎ endometriosis, pelvic infection, smoking, DM and obesity • Socioeconomic factors ฎ poor nutrition, poor health, delay in marriage

  4. T.B.L. Kirkwood, 1998 Mechanisms of aging - oxidative damage free radicals - accumulation of aberrant proteins - defective mitochondria accumulate in cells - DNA damage - mutations (Maturitas 1998; 30: 105-11)

  5. M.Dorland et al., 1998 There might be a relationship between ageing and ovarian ageing (Maturitas 1998; 30: 113-8)

  6. EFFECT OF AGE ON THE COMPONENTS OF THE FEMALE REPRODUCTIVE SYSTEM

  7. OVARY • ovarian function • - the quality and quantity of oocytes released • - the hormonal milieu of the • preovulatory follicle and • postovulatory corpus luteum and • its progesterone production

  8. Kathleen A. O’Connor et al, 1998 The inactive phase of the menstrual cycle - no follicles are growing or matured to the point of producing estradiol - loss of feed back control on LH and FSH - the younger age, this phase is effectively of leugth zero (Maturitas 1998; 30: 127-36)

  9. Alain Gougeon, 1998 - the numbers of growing follicles decrease with ageing, especially in women over the age of 40 - selective follicles exhibit a mitotic activity of their granulosa cell higher in women older than 40 years than in younger women (Maturitas 1998; 30: 137-42)

  10. EFFECT OF AGE ON OVARY - ฏ oocyte reservoir - ฏ oocyte quality - ฏ ovarian responsive to gonadotropic stimulation - ฏ ovarian blood flow - shorter and irregular menstrual cycle 3-9 yrs before menopause - ญ FSH - LH levels remains unchanged

  11. SIGNS OF OVARIAN AGING - ฏ follicular inhibin ฎ theearliest sign - ญ early follicular serum FSH - FSH > 15 IU/L ฎ predictive value for poor reproductive potential and decrease in the number of oocytes ฎ ฏfertility rate - FSH>25 IU/L ฎ a zero pregnancy rate - quality of the oocytes correlates negatively with age, particularly for women older than 38 years

  12. Clomiphene citrate challenge test (CCET) -intake of 100 mg of clomiphene citrate D5-9 - measure serum FSH D10 - FSH < 20IU/Lฎ normal response - FSH > 20IU/L ฎ ฏ ovarian reserve - 3% before age of 30 years - 7% at 30-34 years of age - 10% at 35-39 years of age - 26% at 40 years of age and after

  13. GnRH agonist stimulation test -leuprolide acetate (1.0 mg/ml) on D2 - measure estradiol 24 hr later - change in estradiol < 15 pg/ml ฎ pregnancy rate < 5% - change in estradiol > 100 pg/ml ฎ pregnancy rate of 35%

  14. Factors that may be used to predict faster oocyte depletion • early menarche • age at last pregnancy • poor nutrition • smoking • family Hx of early menopause

  15. Older women • Non growing follicles enter the growing pool at an accelerated rate • ฏ quality of the oocytes • chromosomal anomalies • ฏ implantation rate

  16. Uterus • some studies suggest a decrease in uterine receptivity with age, but most studies do not • age does not seem to affect the endometrial thickness • leiomyomas, endometrial hyperplasia & polyps which increases with age • ฎ may influence implantation

  17. Hypothalamus • has not been adequately studied among human • positive and negative feedback mechanism seems to remain intact with advancing age • biologic activity of the secreted gonadotropins may change with age • less than that of younger women • ญ fibrosis of the pituitary gland after • 4th decade of life

  18. Cervix • endocervical cells height • the stroma of the cervix changes from reticular connective tissue to collagen connective tissue • produces noncyclic secretions

  19. Fallopian tubes • tubal motility is influenced by age and menopause • transportation of an ovum • - muscular wall contractility • - ciliary activity ฎ not contain estrogen • & progesterone receptors • - secretion of the oviduct • - diameter of the lumen

  20. Fecundability rate • is the probability of conceiving during one menstrual cycle • the observed conceptions during a number of cycles and dividing it by the total number of menstrual cycles of women who engage in sexual intercourse and do not practice contraception

  21. Fertility rate • is the probability of conceiving within 1 year within a given population • the number of livebirths in 1 year and dividing it by the total population of women in the reproductive age group.

  22. Figure 1. Fertility rate among natural populations and a U.S population

  23. Figure 2. Pregnancy rate per cycle among infertile patients undergoing various treatments.

  24. E.R. te Velde, 1998 • Until age 30 fecundity is optimal, • starting to decrease thereafter • the monthly fecundity rate at age 35 • = 50% of age 30, has dropped to • 25% at 38 and 0% at about age 41-42 • age-dependent decline of fecundity probably is a matter of very early fetal loss rather than subfertility per se • (Maturitas 1998; 30: 103-4)

  25. Samuel F. Marcus at al, 1996 • fertility does not depend merely on oocyte age and quality but also on uterine age • although ovarian reserve declines with age, it is a biological and not just a chronological function

  26. Results of IVF in women aged > 40 yr • Preg rate Live birth rate • < 25 yr 21.2 % 17.2 % • 40-44 yr 9.5 % 6.3% • > 45 yr 3.1 % 2.3 % Human Fertilisation and Embryology Authority, 1995

  27. Age is associated with poor IVF outcome • poor responsiveness to ovarian • stimulation drugs • rate of cycle cancellation • egg and embryo quality • implantation rate • rate of abortion

  28. EFFECT OF AGE ON MALE FERTILITY • the role of the age of the male partner in fertility is not known • by the age of 65 years the fertility rate of men had dropped to 36% of that among men between 20-24 years • ญ serum LH and FSH concentration • ญ LH pulse frequency and duration, • ฏ amplitude • ฏ spermatogenesis, total sperm count, sperm motility and morphology

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