What is the significance of Anti-Mullerian Hormone (AMH) levels in females of reproductive age, particularly those with a history of infertility or Polycystic Ovary Syndrome (PCOS)?

Significance of Anti-Müllerian Hormone (AMH) Levels

AMH is the best currently available biomarker for assessing ovarian reserve in women ≥25 years, reflecting the quantity of remaining primordial follicles and predicting reproductive lifespan, though it does not indicate oocyte quality or pregnancy chances. 1, 2, 3

Primary Clinical Applications

Ovarian Reserve Assessment

• AMH directly correlates with the size of the antral follicle pool and accurately reflects the remaining primordial follicle reserve, making it superior to age, basal FSH, estradiol, and inhibin B for ovarian reserve evaluation 4, 3
• AMH levels inversely correlate with age (r = -0.52), declining slowly after early adulthood until becoming undetectable approximately 5 years before menopause 3, 5
• Very low AMH levels (<0.7 ng/mL) indicate incipient ovarian insufficiency and represent the best endocrine marker for age-related decline in ovarian reserve 6
• AMH does not vary significantly by menstrual cycle day and is not affected by exogenous estrogen or progesterone use, providing consistent measurement throughout the cycle 4, 6

Infertility Evaluation and IVF Treatment

• AMH predicts ovarian response to stimulation and helps determine appropriate gonadotropin dosing in IVF, with a cut-off of <1.0 ng/mL predicting poor ovarian response (≤3 retrieved oocytes) in women over 40 7, 2
• AMH positively correlates with the number of oocytes retrieved during IVF (P < 0.0001), making it valuable for counseling patients about expected treatment response 7, 3
• Women with AMH <1 ng/mL should pursue fertility evaluation and attempts promptly due to shortened reproductive window 6
• Despite low AMH levels, pregnancy remains possible even with extreme values (<0.4 ng/mL) in women over 40, demonstrating that AMH reflects quantity but not oocyte health 7, 2

PCOS Diagnosis and Evaluation

• AMH levels are significantly elevated in PCOS patients (10.0 ± 2.28 ng/mL), approximately 2-3 times normal values, serving as a potential alternative or adjunct to ultrasound for detecting polycystic ovarian morphology 8, 1, 5
• Five out of six patients with AMH >10 ng/mL were confirmed to have PCOS on pelvic ultrasound (P < 0.05) 5
• However, AMH should NOT be used as a standalone diagnostic test for PCOS due to significant overlap in values between women with and without PCOS, lack of standardization across assays, and absence of established cut-offs 8, 1
• AMH must NOT be used for PCOS diagnosis in adolescents within 8 years of menarche due to overlap with normal physiological values 1

Miscarriage Risk Stratification

• Women with severely low AMH (<0.7 ng/mL) face 91% increased odds of miscarriage, and in women ≥35 years, low AMH confers 85% increased miscarriage risk 6
• Low serum AMH concentration (<1.0 ng/mL) is associated with significantly higher risk of miscarriage (OR 1.35; 95% CI, 1.10–1.66; P=0.004) in women achieving pregnancy through ART 4

Post-Cancer Treatment Monitoring

• AMH is recommended for evaluating ovarian reserve in cancer survivors treated with alkylating agents and/or radiotherapy, with potential recovery observed after low-dose chemotherapy 4, 1
• AMH shows promise as a predictor of timing of menopause onset in pediatric cancer patients, though it will likely be included in long-term follow-up recommendations in the near future 4

Critical Limitations and Caveats

Assay Standardization Issues

• The lack of an international standard for AMH limits comparison between different assays, and direct comparison of results remains problematic 1, 3
• AMH assays display differential responses to pre-analytical factors and show appreciable sample-to-sample variability 1

Clinical Interpretation Pitfalls

• AMH is a marker of oocyte quantity only and does not reflect oocyte health, quality, or actual chances for conception—age remains the strongest driver of fertility treatment success 2
• AMH levels must be interpreted in context of the endogenous endocrine environment; low FSH from hypogonadotropic hypogonadism or hormonal contraceptive use may artificially lower AMH without reflecting true ovarian reserve 2
• Progestin-only contraceptives (like Implanon) suppress the hypothalamic-pituitary-ovarian axis, making AMH and other hormone levels unreliable for PCOS diagnosis while in place—the implant should be removed or allowed to expire before testing 8
• There is an inverse correlation between body mass index and AMH that does not reflect actual ovarian response 2

Age-Specific Considerations

• AMH is most reliable in women ≥25 years where it inversely correlates with age and provides information about remaining reproductive lifespan 1
• AMH should NOT be used routinely for preconception counseling in young, fertile women under 25 years due to limited value and potential fluctuations in this population 1
• Age-specific reference ranges are essential when interpreting AMH levels, as values naturally decline with age and normative data in pediatric patients remain limited 4, 1

Inappropriate Uses

• AMH screening before fertility treatment should be used to estimate expected response and not to withhold treatment, as even extremely low levels do not preclude pregnancy 7, 2
• At-risk postpubertal females without signs of premature ovarian insufficiency who desire fertility assessment should be referred for specialist consultation rather than relying on AMH alone 1

Clinical Decision Algorithm

For women ≥25 years with infertility or PCOS concerns:

1. Measure AMH using liquid chromatography-tandem mass spectrometry (LC-MS/MS) when available, ensuring no hormonal contraception is in use 8, 2
2. Interpret results in age-specific context:
   • AMH <0.7 ng/mL: Severely diminished reserve, urgent fertility evaluation, discuss oocyte cryopreservation 6
   • AMH <1.0 ng/mL: Poor ovarian reserve, expect reduced IVF response, pursue fertility attempts promptly 6, 7
   • AMH 2.0-6.8 ng/mL: Normal range 5
   • AMH >10 ng/mL: Strongly suggestive of PCOS, confirm with ultrasound and clinical criteria 8, 5
3. Combine AMH with antral follicle count via transvaginal ultrasound (≥8 MHz) for comprehensive ovarian reserve assessment in adults 4, 8
4. For PCOS diagnosis, require at least two of three Rotterdam criteria (oligo/anovulation, clinical/biochemical hyperandrogenism, polycystic ovarian morphology), not AMH alone 8