Effect of age on response to human menopausal gonadotropin stimulation

Conception rates decline in the latter part of the reproductive years. To examine which ovarian parameters are altered with aging, 486 cycles from 225 ovulatory infertile women undergoing human menopausal gonadotropin (hMG) superovulation and washed intrauterine insemination were analyzed. Infertility factors included endometriosis (68%), unexplained infertility (8.4%), male factor (12.9%), and ovulatory dysfunction (10.7%). Parameters that demonstrated a linear relationship with increasing age included numbers of ampules of hMG required per cycle (r = 0.79; P < 0.05), days of stimulation (r = 0.73; P < 0.01), estradiol level at the time of hCG (r = -0.92; P < 0.0001), number of follicles larger than 15 mm (r = -0.61; P < 0.05), and rate of rise of estradiol (r = -0.92; P < 0.0001). These same age-dependent changes were observed in women receiving a standard stimulation protocol (3 ampules hMG beginning on cycle day 2). When standard cycles were limited to the first cycle only, the preovulatory estradiol (r = -0.92; P < 0.005), slope of estradiol rise (r = -0.92; P < 0.005), and number of preovulatory follicles (r = -0.92; P < 0.005) still showed a significant decrease with age. Although the mean estradiol level per preovulatory follicle showed a slight decrease with maternal age, no statistically significant trend was noted. In addition, the cycle day of hCG administration was unaffected by age. With advancing age, there appears to be a decreased ovarian response to an increased amount of stimulation, as measured by steroidogenesis and follicular recruitment; yet the estradiol/follicle remains unaltered, indicating continued health of the follicle. These observations may explain in part the observed decrease in fecundity in older women.