New AMH Complex May Transform Fertility Testing

Anti-Müllerian hormone (AMH), a crucial biomarker for assessing ovarian reserve, has long played a pivotal role in assisted reproductive technologies and women's reproductive health management. However, the scientific community has debated the true active form of AMH. A recent study suggests that AMH's non-covalent complex may be its biologically active form, potentially revolutionizing AMH testing and related treatments.

As a member of the transforming growth factor β (TGFβ) superfamily, AMH is a glycoprotein composed of two 55 kDa N-terminal homodimers and two 12.5 kDa C-terminal homodimers. Traditional understanding held that these dimers connected through non-covalent disulfide bonds. The new research challenges this paradigm, demonstrating that the C-terminal homodimer exhibits significantly lower activity compared to the non-covalent complex. Remarkably, when the C-terminal homodimer recombines with the N-terminal proregion to form the complex, nearly full biological activity is restored. This breakthrough strongly indicates that AMH's non-covalent complex serves as its primary bioactive form.

Current AMH testing primarily measures total concentration without distinguishing between active and inactive forms. If confirmed, this discovery would shift diagnostic approaches toward detecting the active complex, enabling more accurate ovarian function assessment and fertility prediction. Such advancement could significantly improve guidance for assisted reproductive therapy, polycystic ovary syndrome (PCOS) risk evaluation, and menopause age prediction.

The findings also open new avenues for pharmaceutical development. Drugs targeting the AMH non-covalent complex could more effectively modulate AMH's biological activity, potentially treating AMH-related conditions including premature ovarian insufficiency and PCOS.

While the study provides crucial insights into AMH's active form, numerous questions remain unanswered. Key areas for future investigation include the formation mechanism of AMH non-covalent complexes, factors influencing complex stability, and the interconversion dynamics between different AMH forms in vivo. Addressing these questions will deepen our understanding of AMH's biological functions and facilitate more effective diagnostic and therapeutic approaches.

The identification of AMH's non-covalent complex as the probable active form represents a paradigm shift in reproductive endocrinology. As research progresses, this discovery may lead to more precise AMH testing methods and targeted therapies, ultimately advancing women's reproductive healthcare.