Anti-Müllerian Hormone

Anti-Müllerian hormone (AMH) is a glycoprotein of the transforming growth factor beta family. In women it is secreted by granulosa cells of preantral and small antral follicles (2 to 8 mm), and the serum level reflects the number of growing follicles, which tracks the primordial follicle pool (ovarian reserve). It is measured by automated immunoassay (ng/mL or pmol/L; 1 ng/mL equals 7.14 pmol/L).

Unlike FSH and oestradiol, AMH varies little across the menstrual cycle, so it can be sampled on any day. In men, Sertoli cells secrete AMH, with high levels in childhood falling at puberty, and it is used in disorders of sex development.

AMH is used to estimate ovarian reserve before fertility treatment, to predict response to ovarian stimulation, to support the diagnosis of polycystic ovary syndrome and premature ovarian insufficiency, to monitor granulosa cell tumours, and to assess testicular function in children.

It predicts the quantity of oocytes, not their quality, and it does not predict the chance of natural conception in women without infertility.

About 1 in 100 women have premature ovarian insufficiency before age 40 years, and polycystic ovary syndrome affects 6 to 13% of women of reproductive age.

Indications. Women planning fertility treatment (to choose the stimulation dose and predict poor or excessive response). Infertility workup. Suspected diminished ovarian reserve or premature ovarian insufficiency. Polycystic ovary syndrome (supporting test). Before and after gonadotoxic chemotherapy, ovarian surgery or radiotherapy. Follow up of granulosa cell tumour. Boys with cryptorchidism, anorchia or ambiguous genitalia, and girls with suspected ovarian disorders.

Specimen. Serum 1 mL, any day of the cycle, no fasting. Stable for several days at 2 to 8 °C. Ideally taken off hormonal contraception for 1 to 2 months, because it can lower levels. Use of the same assay for serial measurements.

Women (typical values, assay dependent).

Ovarian reserve categories (adult women of reproductive age).

• Very low or undetectable: under 0.3 ng/mL (under 2 pmol/L). Predicts very poor response, and suggests near menopause or premature ovarian insufficiency.
• Low: 0.3 to 1.0 ng/mL (2 to 7 pmol/L). Diminished ovarian reserve and likely poor response (fewer than 4 oocytes).
• Normal: 1.0 to 3.5 ng/mL (7 to 25 pmol/L). Expected normal response.
• High: over 3.5 ng/mL, and over 5 ng/mL (over 35 pmol/L) suggests risk of ovarian hyperstimulation syndrome.
• Very high: over 7 to 10 ng/mL, consistent with polycystic ovary syndrome (levels 2 to 3 times the age matched mean), or rarely a granulosa cell tumour.

Clinical use.

• Poor response to ovarian stimulation (fewer than 4 oocytes): AMH under 1.0 ng/mL (sensitivity and specificity about 80 to 90%).
• Prediction of hyper-response: AMH over 3.5 to 5 ng/mL. Gonadotrophin doses are reduced and antagonist regimens with a lower risk trigger are used.
• Polycystic ovary syndrome: AMH over 3.2 to 4.7 ng/mL (varies by assay) has sensitivity and specificity of 80 to 90% for polycystic ovarian morphology, and can replace follicle counting in some adult criteria.
• Premature ovarian insufficiency: AMH is very low or undetectable, with FSH over 25 IU/L on two samples at least 4 weeks apart and amenorrhoea or oligomenorrhoea for 4 months.
• Menopause timing: AMH under 0.1 ng/mL predicts menopause within 5 years, and undetectable AMH confirms the post-menopausal state in most cases.
• Chemotherapy and surgery: levels fall after alkylating agents, ovarian cystectomy and radiotherapy, and recovery is variable.
• Granulosa cell tumour: AMH is raised and falls after resection, a recurrence marker with sensitivity of 76 to 90%.

Men and children.

• Boys: AMH is high before puberty (over 50 ng/mL), falling to 3 to 10 ng/mL in adults. Low AMH with high FSH points to testicular failure or anorchia. High AMH with undescended testes indicates present testicular tissue.
• Girls: AMH is low in childhood and rises through puberty. A raised AMH in girls with virilisation may reflect polycystic ovary syndrome.
• Disorders of sex development: AMH separates testicular tissue (AMH detectable) from gonadal dysgenesis, and persistent Müllerian duct syndrome shows low or absent AMH or receptor mutation.

Critical values and findings needing immediate action.

• AMH over 5 ng/mL in an assisted conception cycle: high risk of ovarian hyperstimulation syndrome, adjust dosing and consider freeze all strategy.
• Undetectable AMH under age 40 years with amenorrhoea: premature ovarian insufficiency, with FSH, karyotype, fragile X premutation and 21-hydroxylase or adrenal antibody testing, and early hormone replacement for bone and cardiovascular protection.
• Markedly raised AMH (over 20 ng/mL) with pelvic mass or postmenopausal bleeding: suspected granulosa cell tumour, imaging and gynaecological oncology referral.
• Pre-chemotherapy AMH low: urgent fertility preservation discussion before treatment.

Interferences and pitfalls.

• AMH reflects quantity, not oocyte quality, and does not predict spontaneous pregnancy in women with normal fertility, so it should not be used to counsel against conception in women under 35 years without infertility.
• Assays differ. Older manual assays give different results from newer automated assays, and results are not interchangeable. Some older assays showed artefactual lowering in stored or complement activated samples.
• Hormonal contraceptives, GnRH agonists and pregnancy lower AMH. Levels recover within 1 to 3 months after stopping contraceptives.
• Obesity and smoking lower AMH. Vitamin D deficiency, endometriosis and ovarian surgery are linked to lower values.
• Polycystic ovary syndrome raises AMH, and a high result does not guarantee a good response (the quality is variable).
• Intraindividual variation is up to 20 to 30% and results can change between samples.
• AMH under the age range predicts earlier menopause but cannot give the exact timing.
• Fertility decisions combine age, antral follicle count, AMH, FSH and history.

Special groups.

• Adolescents: AMH is higher in early reproductive years, and reference intervals apply from age 18 years.
• Women with Turner syndrome: low or undetectable AMH, with some mosaic women retaining detectable levels.
• BRCA mutation carriers: AMH may be lower, with earlier decline.
• Cancer survivors: AMH is used to estimate residual reserve.
• Regions: access to AMH testing and fertility services is variable.

Follow up tests. FSH, LH and oestradiol on day 2 to 5 of the cycle, inhibin B, antral follicle count by transvaginal ultrasound, TSH and prolactin, testosterone and 17-hydroxyprogesterone, karyotype and fragile X (FMR1) premutation testing in premature ovarian insufficiency, adrenal and ovarian antibodies, bone densitometry, and pelvic imaging.