300 likes | 557 Views
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.
E N D
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
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
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)
M.Dorland et al., 1998 There might be a relationship between ageing and ovarian ageing (Maturitas 1998; 30: 113-8)
EFFECT OF AGE ON THE COMPONENTS OF THE FEMALE REPRODUCTIVE SYSTEM
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
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)
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)
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
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
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
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%
Factors that may be used to predict faster oocyte depletion • early menarche • age at last pregnancy • poor nutrition • smoking • family Hx of early menopause
Older women • Non growing follicles enter the growing pool at an accelerated rate • ฏ quality of the oocytes • chromosomal anomalies • ฏ implantation rate
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
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
Cervix • endocervical cells height • the stroma of the cervix changes from reticular connective tissue to collagen connective tissue • produces noncyclic secretions
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
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
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.
Figure 1. Fertility rate among natural populations and a U.S population
Figure 2. Pregnancy rate per cycle among infertile patients undergoing various treatments.
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)
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
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
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
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