The purpose of using ovarian reserve testing as a screening test is to identify infertility patients at risk for decreased ovarian reserve, who are likely to exhibit a poor response to gonadotropin stimulation and to have a lesser chance of achieving pregnancy with IVF. Good screening tests have validity as measured by sensitivity and specificity. A valid test correctly categorizes persons who have disease as test positive (highly sensitive) and those without disease as test negative (highly specific).

For clinical purposes, specificity is the test characteristic that should be optimized to decrease false positives, or wrongly categorizing patients with normal ovarian reserve as having decreased ovarian reserve (DOR ) . Graphically, the sensitivity and specificity of different cutpoints of a diagnostic test can be plotted as receiver operating characteristic (ROC) curves .

Positive predictive value (PPV ) and negative predictive value (NPV ) are screening test characteristics that change with the prevalence of disease (DOR ) in the study population. The PPV is the probability that a woman who tests positive truly has DOR. The NPV is the probability that a woman who tests negative has normal ovarian reserve. Ovarian reserve testing is most useful in identifying DOR in women at high risk for DOR. Ovarian reserve testing in women at low risk for DOR will yield a larger number of false-positive results (lower PPV).

As the ovary ages, the size of the follicle pool declines. Fewer follicles result in less production of AMH and inhibin. Because of lower inhibin levels, FSH rises prematurely or more rapidly leading to elevated early follicular phase serum FSH levels. Premature and rapid follicular growth results in elevated early follicular phase estradiol levels and a shortened follicular phase and overall shortened menstrual cycle. A short menstrual cycle length is associated with a lower probability of conceiving naturally or following IVF [5]. The cutoff value to define “short” cycle length varies by study ranging from 25 to 26 days.

Estradiol levels vary over the course of a menstrual cycle, peaking in both the late follicular and mid-luteal phases. As ovarian reserve declines, the follicular phase shortens because of decreasing feedback inhibition by follicles recruited during the previous cycle. As a result, an elevated day 3 estradiol level could reflect diminishing ovarian reserve.

Estradiol is released from the ovary during follicular development. The estradiol level is usually low (<50 pg/mL) on days 2–4 of the menstrual cycle. An elevated value (>60–80 pg/mL) in the early follicular phase can indicate reproductive aging and hastened oocyte development. Through central negative feedback, a high estradiol level can suppress an elevated FSH concentration into the normal range. The value of obtaining an estradiol level is that it allows the correct interpretation of a normal basal FSH level. Basal estradiol has low predictive accuracy for poor ovarian response and failure to conceive and, therefore, this test should not be used in isolation to assess ovarian reserve [9].

AMH is a homodimeric glycopeptide that is produced predominantly by granulosa cells. AMH is believed to downregulate FSH -mediated folliculogenesis. AMH expression is highest in secondary, preantral, and small antral follicles. AMH seems to have a role in selecting the dominant follicle in addition to generally mediating preantral follicular recruitment. AMH levels start undergoing a log-linear decline approximately 15 years prior to menopause and drop to very low levels approximately 5 years before menopause [10].

The anti-Müllerian hormone concentration is fairly stable within and between menstrual cycles [11]. As the number of ovarian follicles decreases with age, a concomitant decrease in AMH levels occurs, which reflects this age-related oocyte depletion [12]. Although an undetectable AMH level suggests diminished ovarian reserve and can identify individuals at risk of poor ovarian response to stimulation, undetectable and low AMH levels (0.2–0.7 ng/mL DSL ELISA) are not predictive of failure to conceive [13]. AMH levels may allow treatment to be tailored to each individual. Lower AMH levels are associated with reduced ovarian response to stimulation and high levels are associated with a brisk ovarian response to stimulation [13]. Although the AMH level is a good predictor of oocyte quantity, it may not provide information about egg quality. Young women with low AMH levels may have a reduced number of oocytes, but normal age-appropriate oocyte quality [14].

One limitation of AMH level testing is the variability of results between the available assays. In clinical practice, individual AMH level test results must be interpreted based on the normal range of the assay used [15]. AMH level testing is a useful screening test in women at high risk of diminished ovarian reserve and in women undergoing IVF [16, 17].

The nonpregnancy predictive value of a low AMH value appears to increase if older women at risk for ovarian aging are tested. The use of AMH as a routine screening tool for DOR in a low-risk population is not recommended.

AMH level testing may be valuable in assessing ovarian reserve in young women with cancer before and after chemotherapy [18]. AMH may enable assessment of ovarian reserve before and after ovarian surgery and for women at high risk of primary ovarian insufficiency. AMH level testing may in future provide an accurate method of predicting the reproductive lifespan and the timing of menopause [19].

AMH has the advantage over FSH in that AMH levels remain relatively stable over the menstrual cycle, thus measurement does not need to be cycle day specific. A recent meta-analysis of earlier studies showed no significant association between AMH, modeled as a continuous variable, and pregnancy following ART [20]. However, more recent studies of larger sizes, modeling AMH using cutoff values, have shown lower odds of pregnancy and live birth following ART among women with low AMH levels [21–24].

High AMH values are associated with polycystic ovary syndrome (PCOS) and may identify women at risk for OHSS . It is believed that AMH remains a valid assay even when ovarian suppression occurs through oral contraceptives, although age-specific AMH percentiles decrease by 11% with oral contraceptives . [25].

Inhibin B is a glycoprotein hormone that is secreted primarily by preantral and antral follicles. The serum concentration of inhibin B decreases with the age-related decrease in the number of oocytes. Inhibin B has central negative feedback that controls FSH secretion. Therefore, a decrease in inhibin B levels leads to increased pituitary FSH secretion and higher early follicular FSH levels.