What are the treatment options for a female patient with low Anti-Mullerian Hormone (AMH) levels?

Management of Low Anti-Müllerian Hormone (AMH) Levels

Patients with low AMH require immediate referral to reproductive endocrinology or gynecology for comprehensive evaluation, hormone replacement therapy if indicated, and urgent fertility counseling, as low AMH indicates diminished ovarian reserve with reduced fertility potential. 1

Immediate Specialist Referral

All patients with low AMH need prompt specialist evaluation to determine the underlying cause and appropriate management strategy. 1

• Reproductive endocrinology referral is warranted for infertility evaluation, assisted reproduction consultation, gestational surrogacy options, and fertility preservation strategies 1
• Endocrinology or gynecology referral is indicated for patients with delayed puberty, persistently abnormal hormone levels, or confirmed hypogonadism 1
• Even postpubertal females with regular menstrual cycles but a history of gonadotoxic treatment require referral, as they remain at risk for premature ovarian insufficiency 1

Diagnostic Workup to Confirm Ovarian Status

The specialist should perform comprehensive hormonal and imaging evaluation to determine the severity of ovarian dysfunction:

• FSH, LH, and estradiol levels should be measured, with elevated FSH and low estradiol confirming premature ovarian insufficiency 2, 3
• Repeat FSH measurement is recommended for diagnostic confirmation, as elevated LH provides stronger discrimination for POI diagnosis 2, 3
• Karyotype analysis is required to exclude Turner syndrome or other chromosomal abnormalities 2, 3
• Fragile X premutation testing is recommended as a genetic cause of POI 2, 3
• Thyroid function tests are necessary to evaluate for autoimmune oophoritis 2, 3
• Bone mineral density (DEXA scan) is required to assess for osteoporosis from chronic estrogen deficiency 2, 3

Hormone Replacement Therapy

HRT is the cornerstone of treatment for patients with confirmed hypogonadism or premature ovarian failure to normalize ovarian hormone levels and prevent long-term complications. 1, 2, 3

• HRT prevents osteoporosis, cardiovascular disease, and sexual dysfunction in patients with estrogen deficiency 2, 3
• Progesterone therapy is mandatory in women with an intact uterus to avoid unopposed estrogen effects and prevent endometrial hyperplasia 1, 3
• HRT regimens differ significantly between survivors who were prepubertal before gonadotoxic therapy versus those who experience gonadal failure after menarche 1
• In pubertal patients, timing and tempo of estrogen HRT are crucial to ensure acceptable final height and should be managed by providers with expertise in pediatric development 1

Fertility Counseling and Reproductive Options

Women with low AMH who desire future pregnancy require urgent fertility counseling, as low AMH indicates diminished ovarian reserve with reduced fertility potential. 1

Critical Contraception Counseling

• Contraception is mandatory even in patients with low AMH and amenorrhea, as spontaneous pregnancy can occur in 5-10% of POI cases despite severely diminished ovarian reserve 1, 2, 3
• All patients need contraception counseling because alkylator-associated gonadal toxicity is extremely variable 1
• Case reports demonstrate that even patients with negligible AMH levels (0.072 ng/mL) have achieved spontaneous conception multiple times 4

Fertility Preservation and Treatment Options

• Oocyte cryopreservation should be considered for patients wishing to preserve fertility options 1
• Prompt fertility evaluation and attempts are recommended for women with diminished ovarian reserve 1
• If natural fertility is desired, specialized reproductive medicine intervention can achieve successful pregnancy outcomes even in patients with rapidly declining and persistently low AMH levels 4
• For confirmed POI, fertility options include oocyte donation, gestational surrogacy, or adoption 2, 3
• Women with extremely low AMH values (≤0.4 ng/ml) can still achieve reasonable clinical pregnancy rates with IVF, particularly those younger than 35 years (27% pregnancy rate) 5

Important Clinical Caveats

AMH Limitations in Specific Populations

Clinicians should exercise caution when interpreting AMH in certain clinical contexts, as AMH may not accurately reflect the primordial follicle pool in all situations:

• In patients with idiopathic hypogonadotropic hypogonadism, AMH levels may underestimate ovarian reserve due to lack of FSH-dependent growing follicles, and AMH can increase substantially with gonadotropin stimulation 6, 7
• AMH only reflects the growing follicular pool responsive to gonadotropins, not solely the underlying primordial pool 6
• AMH has limitations in predicting pregnancy in the general population, as it does not assess oocyte or embryo quality 8

Special Considerations for Cancer Survivors

• AMH levels may recover after low doses of alkylating chemotherapy 1
• Survivors treated with alkylating agents or radiotherapy potentially exposing the ovaries should receive counseling regarding POI risk and fertility implications 9
• Gonadotropin-releasing hormone agonist treatment before gonadotoxic therapy should be considered to attenuate risk of premature menopause 1