In a woman of reproductive age with a low anti‑Müllerian hormone (AMH) level, what are the recommended next steps for evaluation and management?

Evaluation and Management of Low AMH in Reproductive-Aged Women

Initial Assessment

For a woman of reproductive age with low AMH, the first step is to obtain a comprehensive menstrual history and measure FSH and estradiol levels during the early follicular phase (cycle days 2-5), or randomly if amenorrheic, to determine whether she has premature ovarian insufficiency or simply diminished ovarian reserve. 1, 2

Critical History Elements

• Menstrual pattern: Document cycle regularity, any changes in flow or frequency, and presence of amenorrhea (primary or secondary) 1
• Symptoms of estrogen deficiency: Hot flashes, night sweats, vaginal dryness, sexual dysfunction 1
• Reproductive history: Prior pregnancies, time to conception, miscarriages 1
• Gonadotoxic exposures: Prior chemotherapy (especially alkylating agents), pelvic radiation, ovarian surgery 1
• Age context: AMH interpretation is only validated in women ≥25 years; below this age, low AMH does not reliably indicate reduced fertility 1, 3

Essential Laboratory Evaluation

• FSH and estradiol: Measure on cycle days 2-5 (or randomly if amenorrheic) to diagnose premature ovarian insufficiency (POI), defined as FSH >25-40 mIU/mL on two occasions at least one month apart 1, 2
• TSH and prolactin: Rule out thyroid disease and hyperprolactinemia as reversible causes of ovarian dysfunction 2
• Consider transvaginal ultrasound: Antral follicle count (AFC) correlates strongly with AMH and provides additional ovarian reserve assessment; AFC <5 indicates diminished reserve 2

Interpretation of Low AMH

Age-Dependent Thresholds

• AMH <0.7 ng/mL: Indicates severely diminished ovarian reserve and incipient ovarian insufficiency 3
• AMH 0.7-1.0 ng/mL: Indicates diminished ovarian reserve 3, 4
• AMH <0.4 ng/mL: Signifies significantly diminished reserve with reduced fertility potential in women ≥25 years 3
• **AMH <0.01 ng/mL**: Represents extremely low reserve with >80% risk of amenorrhea if exposed to gonadotoxic therapy 3

Important Caveats

• Assay variability: Different AMH assays yield varying results; interpret values using laboratory-specific reference ranges 3, 2
• Hormonal contraception: May lower AMH without reflecting true ovarian reserve 5
• Hypogonadotropic hypogonadism: Low FSH states can suppress AMH independent of actual follicle pool 6, 5
• BMI effects: Inverse correlation between body mass index and AMH does not reflect actual ovarian response 5

Management Algorithm

If Menstruating Regularly with Low AMH

1. Counsel on fertility implications: Women with AMH <1.0 ng/mL have 28% increased miscarriage risk (OR 1.28); those with AMH <0.7 ng/mL have 91% increased risk (OR 1.91) 3, 4
2. Expedite fertility plans: The American Society for Reproductive Medicine recommends women with diminished ovarian reserve pursue fertility evaluation and attempts promptly 4
3. Discuss fertility preservation: Consider oocyte cryopreservation if future fertility desired, especially before any planned surgeries 4
4. Set realistic expectations: While spontaneous pregnancy remains possible even with extremely low AMH, likelihood is significantly reduced 7, 5

If Irregular Menses or Amenorrhea with Low AMH

1. Measure FSH and estradiol: Elevated FSH (>25-40 mIU/mL) on two occasions ≥1 month apart confirms POI 1, 2
2. Refer to specialist: Endocrinologist and/or gynecologist for POI diagnosis and hormone replacement therapy (HRT) initiation 1
3. Initiate HRT if POI confirmed: Estrogen replacement (oral, transdermal, or micronized) plus progesterone (if uterus present) to prevent bone loss, cardiovascular disease, and sexual dysfunction 1
4. Bone density screening: Consider DEXA scan for hypogonadal patients at risk of osteoporosis 1

If Prepubertal or Adolescent

1. Monitor pubertal progression: Assess Tanner staging, menstrual history annually until sexual maturity 1
2. Baseline hormones at age 13: Measure LH, FSH, and estradiol if puberty delayed or arrested 1
3. Refer to pediatric endocrinologist: For delayed puberty (no breast development by age 13) or abnormal hormone levels 1

Specialist Referral Indications

• Reproductive endocrinology: For infertility evaluation, assisted reproduction consultation, or fertility preservation 1
• Gynecology/endocrinology: For delayed puberty, persistently abnormal hormone levels, or confirmed hypogonadism 1
• Immediate referral: If amenorrheic ≥12 months with elevated FSH, or symptomatic estrogen deficiency 1

Contraception Counseling

Critical pitfall: Even women with low AMH and irregular cycles require contraception counseling, as alkylator-associated gonadal toxicity is extremely variable and spontaneous ovulation can occur unpredictably 1, 7

Monitoring Strategy

• If asymptomatic and menstruating: Laboratory surveillance is not recommended as primary screening; testing should be triggered by menstrual changes or POI symptoms 2
• If at risk for POI (prior gonadotoxic therapy): Annual menstrual history assessment; laboratory testing only if menstrual irregularities develop 1
• If on HRT: Cannot reliably assess ovarian function during hormone therapy; FSH unreliable on tamoxifen, oral contraceptives, or GnRH agonists 2

Key Clinical Pearls

• AMH reflects quantity, not quality: Low AMH indicates fewer oocytes but does not predict oocyte health or per-cycle pregnancy chances 5
• Age trumps AMH: Age remains the strongest predictor of fertility success, independent of AMH level 5
• AMH is not diagnostic of POI: FSH elevation defines POI; AMH is a marker of ovarian reserve but not part of POI diagnostic criteria 1, 2
• Spontaneous pregnancy possible: Even with undetectable AMH (<0.01 ng/mL), spontaneous conception has been documented, though likelihood is markedly reduced 7