Anti-Müllerian Hormone (AMH): A Key Biomarker in Reproductive Medicine
Anti-Müllerian Hormone (AMH) is a polypeptide of the transforming growth factor beta (TGFβ) family that is exclusively secreted by granulosa cells of pre-antral and small antral ovarian follicles, serving as a biomarker of ovarian follicular reserve. 1
Physiological Role and Production
AMH plays several important biological functions in the female reproductive system:
- Origin and secretion: Produced solely by granulosa cells of pre-antral and small antral ovarian follicles 1, 2
- Regulatory function: Inhibits the recruitment of primordial follicles out of the resting oocyte pool 1
- Hormonal interaction: May suppress follicle-stimulating hormone (FSH) action, contributing to ovulatory disturbances 1
- Developmental role: Acts as a "follicular gatekeeper" limiting follicle growth initiation and subsequent estradiol production from small antral follicles prior to selection 3
Clinical Applications
AMH has emerged as an important biomarker in reproductive medicine with several key applications:
1. Assessment of Ovarian Reserve
- Reflects the quantity of small antral follicles in the ovaries 2
- Strongly correlates with antral follicle count (AFC) 4
- Decreases with age and becomes undetectable after menopause 2
- May be the best marker reflecting reproductive aging compared to other ovarian tests 5
2. Prediction of Ovarian Response in IVF
- Shows a linear relationship with oocyte yield after ovarian stimulation 3
- Helps identify potential poor responders to ovarian stimulation 5, 3
- Can predict risk of ovarian hyperstimulation syndrome 4, 3
3. Role in PCOS Diagnosis and Management
- Serum AMH levels are significantly higher in women with PCOS compared to normal ovulatory women 1
- Elevated levels reflect both increased number of small antral follicles and intrinsic characteristics of granulosa cells in PCOS 3
- May potentially replace AFC in PCOS diagnosis in the future 3
4. Other Clinical Applications
- Prediction of menopausal transition 5
- Assessment of iatrogenic damage to ovarian follicle reserve 3
- Marker for certain ovarian tumors (granulosa cell tumors) 5
Limitations and Challenges
Several important limitations affect the clinical utility of AMH:
- Assay variability: Lack of international standardization creates problems comparing results between different assays 1, 4, 3
- Technical issues: Sample handling, transport, and storage conditions affect measurements 1
- Age-specific variations: Significant variability in follicle numbers and AMH levels across the lifespan requires age-specific reference ranges 1
- Biological limitations: AMH only reflects the growing follicular pool responsive to gonadotropins, not necessarily the underlying primordial pool 6
- Fluctuations: Recent studies show AMH levels may not be as stable throughout the menstrual cycle as previously thought 6
Clinical Considerations
When interpreting AMH results, clinicians should be aware of:
- AMH levels are highest in early 20s before declining toward menopause 3
- Levels may be affected by hormonal contraceptive use 3
- AMH has limited value in predicting natural fertility or ongoing pregnancy rates 4, 3
- Different assays produce different numerical results due to lack of standardization 1, 4
Future Directions
For AMH to reach its full clinical potential:
- Development of an international reference standard for AMH is urgently needed 1, 3
- Further research on clustering of AMH with other features of PCOS is required 1
- Better understanding of the relationship between AMH and long-term health outcomes is necessary 1
- Improved assay validity and standardization of measurement techniques 3
AMH represents a significant advance in reproductive medicine, allowing assessment of the previously unmeasurable aspects of ovarian follicular development and reserve. With further refinement of measurement techniques and better understanding of its clinical implications, AMH will continue to be an invaluable tool in reproductive medicine.