Emerging research shows AMH is more than a marker of ovarian reserve, revealing an addressable therapeutic target with applications across menopause, oncofertility, and IVF stimulation.
Anti-Müllerian hormone (AMH) has long been used to estimate ovarian reserve. But new research presented at ASRM by David Pépin, PhD, showed compelling preclinical evidence that the AMH pathway can be therapeutically modulated, with potential applications in stimulation strategies, ovarian protection, and menopause.
A Drug-Development Breakthrough
For more than a decade, AMH was viewed as an intriguing but technically unreachable therapeutic axis - pursued by several large pharmaceutical companies but constrained by the instability and poor activity of recombinant AMH. The breakthrough came from the Donohoe and Pépin laboratory at MGH, where targeted protein engineering produced OVI-586, an AMH analog with true drug-like characteristics.
Early Evidence
In mouse studies, OVI-586 suppressed early follicle activation while leaving primordial follicles intact. Primary and secondary follicle counts dropped sharply, and antral follicles fell to nearly zero.
These findings demonstrate AMH’s role as a negative regulator of early follicle activation. The pause is reversible: once AMH exposure stops, follicles re-enter development in a coordinated wave.
AMH-Driven Synchronization Produced a 3× Increase in Egg Yield
The rebound effect following AMH withdrawal led to one of the most discussed data points in the presentation: stimulations timed 30 days after AMH pretreatment generated threefold greater oocyte yield than controls. Diminished-ovarian-reserve models demonstrated approximately a 2× increase. No change to egg quality was observed.
Subsequent non-human primate studies showed that modified AMH can be administered subcutaneously, with a 24-hour half-life, and demonstrated pharmacodynamic signatures of ovarian quiescence and rebound activation upon therapy termination.
Chemotherapy Models Show Up to 3× Greater Preservation of Ovarian Reserve
Chemotherapy-induced primary ovarian insufficiency (ciPOI) remains a significant problem for young cancer patients, with several commonly used agents causing rapid and sometimes irreversible loss of ovarian reserve.
In preclinical oncofertility models, Pépin and others have demonstrated AMH’s ability to significantly protect the ovarian reserve, with benefits observed against doxorubicin, cyclophosphamide, and carboplatin.
In discussing these findings, Pépin pointed to a recent PNAS publication by Nguyen and colleagues showing that AMH may exert a dual protective effect, keeping early follicles in a quiescent state during chemotherapy and supporting recovery afterward.
Can AMH supplementation delay Menopause?
In the natural model for high AMH - polycystic ovary syndrome (PCOS) - women tend to enter menopause two to four years later than their non-PCOS counterparts. This clinical pattern has long suggested that AMH may play a protective role in setting the pace of ovarian aging.
OVI-586 has shown in animal models that sustained AMH signaling can preserve the ovarian reserve for extended periods of time. These findings point to a potential future in which targeted AMH supplementation might help maintain ovarian function longer than is currently possible and delay the onset of menopause.
At this stage, Pépin is particularly optimistic about easing the transition into menopause. The hallmark symptoms of perimenopause stem from erratic follicular recruitment, which produces unpredictable swings in estradiol. In preclinical models, sustained AMH exposure steadies this recruitment pattern and keeps estradiol levels stable. Pépin noted that such stability could meaningfully reduce the hormonal volatility of perimenopause and lead to a smoother, less symptomatic transition.
What Fertility Teams Should Watch For Next
From Granata Bio CEO, Evan Sussman:
“Reproductive hormones have a strong track record as therapeutic agents, but most interventions act only after follicles have already begun to grow. We acquired Oviva because we believe the next breakthrough in women’s health will come from modulating activation of the ovarian reserve. We look forward to working with Dr. Pépin and his team to move this science into the clinic so patients can benefit from his groundbreaking research.”
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