Anti-Mullerian Hormone

Mechanism of Action

• Fetal male sex determination: AMH from Sertoli cells binds AMHR2 on Mullerian duct mesenchyme, activating SMAD1/5/8 and causing apoptosis of Mullerian duct derivatives (fallopian tubes, uterus, cervix, upper vagina)
• Adult female ovary: granulosa cell AMH inhibits FSH-stimulated follicle growth, keeping primordial follicles in quiescence; AMH level directly reflects primordial follicle pool size
• Ovarian reserve marker: AMH declines linearly with age as primordial pool depletes; low AMH predicts poor IVF response; AMH levels correlate with antral follicle count by ultrasound
• Female fertility pharmacology (experimental): exogenous AMH suppresses follicle recruitment during chemotherapy, potentially preserving ovarian reserve
• Male: AMH from Sertoli cells regulates Leydig cell androgen production during postnatal period; AMHR2 on Leydig cells modulates testosterone synthesis

Research Findings

• AMH is the single most predictive biomarker of ovarian reserve, outperforming FSH, inhibin B, and antral follicle count for IVF outcome prediction
• AMH below 0.5-1.0 ng/mL associated with poor ovarian response (less than 3 oocytes) in IVF with >90% specificity
• Recombinant AMH (r-hAMH) injected in mice before chemotherapy preserved 40-60% more primordial follicles vs control, preventing premature ovarian insufficiency
• POLYCYSTIC OVARY SYNDROME (PCOS): AMH 2-3x elevated vs normal women due to increased follicle numbers; AMH measurement now preferred over testosterone for PCOS diagnosis in some guidelines
• AMH stability: unique stability in blood at room temperature (unlike FSH/LH) allows non-fasting, any cycle-day measurement; significant clinical convenience

Research Protocols

• Clinical measurement: serum AMH by automated immunoassay; no cycle-day restriction; reference ranges age-adjusted (peak 25-35 years: 1.0-3.5 ng/mL; poor reserve: <0.5-1.0 ng/mL)
• IVF prediction: AMH <1.0 ng/mL = poor responder; 1-4 ng/mL = normal; >4-5 ng/mL = high responder (PCOS risk)
• Fertility preservation research: recombinant AMH administered before gonadotoxic chemotherapy in preclinical models at 10-40 mcg/mouse IP
• Male fertility: pediatric AMH by immunoassay for undescended testis workup; low AMH in boys suggests absent or non-functioning testes

Interactions

• FSH: AMH suppresses FSH sensitivity of preantral follicles; low AMH allows FSH hyperstimulation; used to personalize IVF FSH dosing
• GnRH agonists/antagonists: AMH remains stable during ovarian stimulation (unlike E2, LH); used to monitor response during IVF cycle
• Oral contraceptives: slightly suppress AMH measured during OCP use; advise stopping OCP 1-3 months before ovarian reserve testing for accurate AMH

Safety Profile

Endogenous glycoprotein; AMH itself not administered therapeutically in humans. Serum measurement: safe blood test. Recombinant AMH for fertility preservation in Phase I/II trials; preliminary safety acceptable. Not for use in pregnancy.

Legal & Regulatory

AMH measurement: routine clinical diagnostic assay (not a therapeutic drug). Recombinant AMH: Phase I/II investigational for chemotherapy-induced ovarian failure prevention.