What is anti‑Müllerian hormone (AMH) and how is it used to assess ovarian reserve and fertility in women?

Anti-Müllerian Hormone (AMH) for Ovarian Reserve Assessment

AMH is the best currently available hormonal marker of ovarian reserve, produced exclusively by granulosa cells of small growing follicles and accurately reflecting the pool of follicles available for recruitment. 1

What AMH Measures

• AMH is a homodimeric glycoprotein secreted by granulosa cells of preantral and small antral follicles in the ovary, providing a quantitative measure of the functional ovarian reserve rather than the total primordial follicle pool. 1, 2

• Serum AMH levels correlate strongly with antral follicle count (AFC), making it a reliable indirect indicator of the number of growing follicles that can potentially ovulate. 1, 2

• AMH reflects the "functional ovarian reserve"—the pool of growing follicles responsive to gonadotropins—but does not directly measure the underlying primordial follicle pool or assess oocyte quality. 1, 3

Key Clinical Advantages

• AMH can be measured at any point in the menstrual cycle because levels do not vary significantly by cycle day, allowing convenient testing without timing restrictions. 1

• Exogenous estrogen or progesterone therapy does not alter AMH concentrations, unlike FSH which requires cycle-specific timing (days 3-6) for accurate assessment. 1

• AMH is superior to age, basal FSH, estradiol, and inhibin B for assessing ovarian reserve in healthy women. 1, 4

Age-Specific Interpretation and Testing Recommendations

For women ≥25 years with regular cycles:

• AMH testing is the preferred initial assessment, with AFC added for comprehensive evaluation. 1
• AMH concentrations peak at approximately 25 years of age and decline with increasing age, making it clinically useful in this population. 1, 5
• Very low AMH levels (below 0.7 ng/mL) indicate ovarian failure or severely diminished ovarian reserve. 1, 4

For women <25 years:

• AMH interpretation is less reliable due to potential fluctuations during the menstrual cycle, and low values do not correlate with reduced fertility in this age group. 1, 5
• AFC by transvaginal ultrasound remains the gold standard for ovarian reserve assessment in younger women. 1

For women with irregular cycles or amenorrhea:

• AMH is particularly useful since it does not require cycle-specific timing, unlike FSH and estradiol. 1

Clinical Applications

Assisted Reproductive Technology (ART):

• AMH is predictive of ovarian response to stimulation and helps identify patients at risk for poor response or ovarian hyperstimulation syndrome (OHSS). 2, 6
• AMH aids in individualizing FSH dosing protocols but has limited value in predicting ongoing pregnancy or live birth rates. 2, 6, 7

Fertility and Miscarriage Risk:

• Women with severely low AMH (<0.7 ng/mL) face 91% increased odds of miscarriage, and those ≥35 years with low AMH have 85% increased miscarriage risk. 4
• In ART cycles, women with low AMH have 35% higher odds of miscarriage (OR 1.35; 95% CI 1.10-1.66) compared to women with higher AMH. 1
• The increased miscarriage risk stems from reduced oocyte quality due to meiotic errors leading to embryonic aneuploidy. 1
• Women with AMH <1 ng/mL should pursue fertility evaluation and attempts promptly. 4

Cancer Survivors:

• AMH serves as a promising biomarker to predict remaining ovarian reserve and estimate timing of menopause onset in adult and pediatric cancer survivors treated with alkylating agents and/or radiotherapy. 1, 5
• Cancer patients typically exhibit decreased AMH levels after treatment, with modest recovery possible following low-dose alkylating chemotherapy. 1

Premature Ovarian Insufficiency (POI):

• AMH can identify women at heightened risk for POI, though it is not incorporated into formal diagnostic criteria. 1
• AMH may detect early declines in functional ovarian reserve before abnormal FSH levels become apparent. 1
• FSH >35 IU/L suggests ovarian failure, but FSH remains a late marker less sensitive than AMH for early detection. 1

Endometriosis:

• The American College of Obstetricians and Gynecologists recommends measuring AMH in all reproductive-age women with diagnosed or suspected endometriosis to establish baseline ovarian reserve. 4
• Fertility preservation options such as oocyte cryopreservation should be discussed before any planned endometrioma surgery, especially in women with low baseline AMH. 4

Important Caveats and Limitations

• AMH assays lack international standardization, so results must be interpreted using laboratory-specific reference ranges, and direct comparison between different assays remains problematic. 1, 5, 2

• AMH only reflects the growing follicular pool responsive to gonadotropins and may not solely reflect the underlying primordial pool, as demonstrated in cases of hypogonadotropic hypogonadism where AMH increases with gonadotropin stimulation. 3

• AMH does not assess oocyte or embryo quality, which limits its ability to predict female fertility in the general population. 7

• In cancer survivors, return of regular menstrual cycles does not reliably indicate normal ovarian reserve; many continue to have compromised ovarian reserve and reduced fertility potential despite menstrual resumption. 1

• AFC by transvaginal ultrasound correlates well with AMH but is operator and equipment-dependent, limiting accuracy and reproducibility. 5