Serum Day 3 Follicule Stimulating Hormone As women age, FSH physiologically rises in the early follicular phase (cycle day 3), with levels of 5.74 IU/L at age 35 to 39 and 14.34 IU/L at age 45 to 59. Higher levels are seen after unilateral oophorectomy. In women in their 40s, levels greater than 20 IU/L are predictive of menopause. Because the incidence of abnormal values is lower in younger women, testing is typically performed for women aged 35 or older (108). In subfertile women with an FSH 8 IU/L or more, spontaneous pregnancy rates decrease by 7% per unit of FSH increase, with a 40% reduction at 15 IU/L and 58% at 20 IU/L (112). FSH levels vary widely by assay, laboratory, and population (109). Because of the poor sensitivity of high basal FSH values in determining fecundability, they should not be used as the sole basis for excluding women from consideration for ART (113). Likewise, the poor specificity of low basal FSH values in determining fecundability makes them unreliable when used to reassure patients, particularly those of increased reproductive age (109).
Basal Estradiol Level Basal day 3 FSH is often combined with estradiol (E2) testing. Estradiol levels on day 3 of the menstrual cycle reﬂect follicular growth rather than the number of antral follicles (114). Elevations in FSH and decreases in inhibin B (see below) that accompany aging results in advanced follicular growth at the end of the preceding luteal phase. In response, early follicular E2 levels are typically higher in older women and in women with advanced reproductive aging (104).
Clomiphene Citrate Challenge Test Clomiphene citrate is thought to have antiestrogenic effects on the hypothalamic–pituitary axis, resulting in a decrease in E2-mediated suppression of FSH production by the pituitary. The clomiphene citrate challenge test (CCCT) involves the measurement of serum FSH and estradiol on day 3 of the menstrual cycle, and again on day 10 after administration of clomiphene citrate (100 mg orally each day) from days 5 to 9. The CCCT has been reported to be more sensitive than basal FSH alone in identifying poor response to exogenous gonadotropins, but others report that the predictive values of the tests do not differ substantially (109,110).
Serum Inhibin B Serum inhibin B is secreted by ovarian granulosa cells starting at the preantral follicle stage and therefore reﬂects the size of the growing follicular cohort (111). Reduced inhibin B levels are seen with aging even in normal fertile women (114). Inhibin B alone has poor predictive value for ovarian response but improves the predictive value when added to the CCCT (109,110). Unlike basal testing, levels of inhibin B measured on the 5th day of ovarian stimulation were predictive of live birth following IVF/ICSI (115).
Serum Antim¨ullerian Hormone Antim¨ullerian hormone (AMH) is produced by the granulosa cells of preantral and small antral follicles (111,114). The serum level of AMH in women with normal cycles declines with age and becomes undetectable after menopause (114,116).
AMH appears to be a good predictor of both excessive (>3.5 ng/mL) and poor (<1 ng/mL) IVF stimulation response and is strongly correlated to the antral follicle count (111,116,117). Unlike other serum markers, AMH can be measured at any time in the menstrual cycle (116).