Anti-Müllerian Hormone (AMH) — 10 Marks

1. Definition and Source

Anti-Müllerian hormone (AMH), also called Müllerian-inhibiting substance (MIS), is a dimeric glycoprotein belonging to the transforming growth factor-beta (TGF-β) superfamily.

In the male fetus: secreted by Sertoli cells of the testes, causing regression of the Müllerian (paramesonephric) ducts, preventing development of the uterus, fallopian tubes, and upper vagina.
In the female: AMH is produced postnatally by the granulosa cells of preantral and small antral follicles (2-6 mm), with little to no production from primordial follicles or large antral/dominant follicles (Berek & Novak's Gynecology, p. 2044).

2. Physiological Role

Fetal life (male): mediates Müllerian duct regression via the AMH type II receptor (AMHR2); mutations cause Persistent Müllerian Duct Syndrome in males.
Postnatal ovary: regulates the transition of primordial follicles into the growing pool and modulates FSH sensitivity of growing follicles, acting as a "gatekeeper" that limits follicular recruitment.
Reflects the size of the resting primordial follicle pool indirectly, since it is secreted only once follicles begin to grow.

3. Characteristics as a Biomarker

Can be measured at any time in the menstrual cycle (unlike FSH/estradiol), showing relatively low intra- and inter-cycle variability - Berek & Novak's Gynecology, p. 2044.
Serum levels decline progressively with reproductive age and become undetectable after menopause.
Interpretation requires age-specific reference ranges; results vary with assay platform (Diagnostic Systems Laboratories, Beckman Coulter Gen II, automated platforms), limiting comparability of serial values across labs.
Strongly correlates with antral follicle count (AFC) on transvaginal ultrasound.

4. Clinical Applications

a) Ovarian reserve testing AMH, along with AFC, is now the standard test of ovarian reserve, superior to day-3 FSH because it is cycle-independent and a more direct reflection of the growing follicle cohort.

Low AMH (<1 ng/mL) predicts poor ovarian response to controlled ovarian stimulation in IVF.
High AMH (>3.5 ng/mL) predicts excessive/hyperresponse, useful for individualizing gonadotropin dosing and anticipating OHSS risk.

b) IVF counseling and protocol selection AMH (with AFC, age, BMI, and reproductive history) is used in prediction models for IVF live-birth probability and to select stimulation protocol/gonadotropin dose; combined AMH/AFC models reclassify a significant proportion of patients compared to age alone (Berek & Novak's Gynecology, p. 2044).

c) PCOS diagnosis Granulosa cells in polycystic ovaries produce excess AMH due to the increased number of small antral follicles; AMH levels are often 2-3 times higher than normal and are being explored as a possible criterion/adjunct to Rotterdam criteria (correlates with AFC and hyperandrogenism).

d) Prediction of age at menopause Declining AMH trajectories can help predict time to menopause, useful in women with a family history of early menopause or before planned fertility-affecting treatment.

e) Fertility preservation counseling Used to assess ovarian reserve before gonadotoxic chemotherapy/radiotherapy and to counsel on fertility preservation options (oocyte/embryo cryopreservation) in oncofertility settings.

f) Tumor marker AMH is a useful serum marker for granulosa cell tumors of the ovary - elevated preoperatively and used to monitor for recurrence post-treatment, since granulosa cells retain AMH-secreting capacity.

g) Disorders of sex development / pediatric urology Measured in evaluation of ambiguous genitalia and intersex conditions - low/absent AMH with intra-abdominal testes suggests Persistent Müllerian Duct Syndrome; presence/absence helps distinguish testicular tissue.

h) Contraception and fertility monitoring Being evaluated as a marker to counsel women on the impact of hormonal contraception on ovarian reserve testing (levels may be mildly suppressed on combined hormonal contraceptives).

5. Factors Affecting AMH Levels

Increased: PCOS, granulosa cell tumors, obesity (variable), younger age.
Decreased: increasing age, smoking, prior ovarian surgery/endometrioma cystectomy, chemotherapy/radiotherapy, primary ovarian insufficiency, hormonal contraceptive use, vitamin D deficiency (debated).

6. Limitations

Not a reliable predictor of natural monthly fecundability or time-to-pregnancy in normal fertile women without infertility history (Berek & Novak's Gynecology, p. 2044).
Assay variability across platforms limits absolute cut-off comparisons between labs.
Does not predict oocyte quality, only quantity of the growing follicle cohort.
Should not be used alone to counsel a woman against attempting pregnancy or to deny fertility treatment.

7. Summary Table

Feature	Detail
Source	Granulosa cells of preantral/small antral follicles
Family	TGF-β superfamily glycoprotein
Cycle variability	Minimal - can test any day
Correlates with	AFC
Main clinical use	Ovarian reserve assessment, IVF response prediction
Other uses	PCOS, menopause prediction, granulosa cell tumor marker, oncofertility counseling, DSD evaluation

Recent literature continues to refine AMH's role, particularly in oncofertility. A 2025 systematic review and meta-analysis (PMID: 40544575) confirmed the significant negative impact of chemotherapy on AMH/ovarian reserve in breast cancer survivors, reinforcing pre-treatment AMH testing for fertility counseling - consistent with, and supportive of, the textbook teaching above.

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