Can finerenone help restore fertility in POI? Early results show follicle growth and IVF-ready eggs in some women.
Scientists at Juntendo University, led by Professor Kazuhiro Kawamura, had earlier created an in-vitro procedure designed to help restore fertility in women with primary ovarian insufficiency (POI). ()
Key Biological Pathways Behind Ovarian Follicle Development
Meanwhile, a research group headed by Professor Kui Liu at the University of Hong Kong (HKU) identified important biological pathways involved in ovarian follicle development. Their work showed that the mTORC1 signaling pathway in granulosa cells and the PI3K pathway in oocytes play key roles in the formation of follicles.
Building on these discoveries, researchers developed an in-vitro activation (IVA) approach. In this technique, small ovarian follicles from patients with POI are stimulated in laboratory-cultured ovarian tissue.
The treated tissue is then reimplanted into the patient through minimally invasive laparoscopic surgery, allowing the follicles to grow and mature. According to Prof. Kawamura, the method has already led to successful pregnancies and live births in some patients.
Understanding Premature Ovarian Insufficiency (POI)
Premature ovarian insufficiency (POI) is a clinically significant cause of infertility that affects between 1 to 3% of women of childbearing age. Symptoms include absent menses, low estrogen levels, and elevated follicle-stimulating hormone (FSH) levels.
Although residual primordial follicles often remain in the ovaries of women with POI, these follicles frequently fail to develop spontaneously. Because FSH levels are already high, the follicles typically do not respond to additional hormonal stimulation used in standard fertility treatments.
Building on these mechanistic insights, the researchers investigated whether an already approved oral medication might stimulate follicle development without requiring invasive procedures. Prof. Kawamura notes that drugs that activate the mTORC1 and PI3K pathways are already used to treat kidney disorders.
Could one such drug be repurposed to restore fertility in women with POI? Prof. Kawamura worked with Prof. Liu’s team to explore this concept. Zexiong Lin and Dr. Yuan Li of Prof. Liu’s team, and Dr. Tianren Wang of HKU – Shenzhen Hospital also contributed greatly to this research effort. Their findings were published on February 5, 2026, in Volume 391, Issue 6785 of the journal Science.
The team identified finerenone as a promising candidate. Finerenone is a mineralocorticoid receptor antagonist known for its antifibrotic properties and favorable safety profile in patients with chronic kidney disease. When ovaries from immature mice were grown in-vitro and dosed with finerenone, they began to develop follicles and eventually mature oocytes.
Encouraged by these findings, the team tested the effects of oral doses of finerenone on mouse fertility. Over an 18-week period, adult mice receiving finerenone gave birth to more offspring than those on a placebo. What’s more, finerenone also induced follicle formation in mice that had grown infertile due to ovarian insufficiency caused by aging.
Gene expression analysis showed that finerenone suppressed the production of collagen in the ovarian cortex. Excess collagen deposition contributes to tissue stiffening (fibrosis), which may physically restrict small follicle growth.
Antifibrotic Effects of Finerenone May Support Fertility
“Finerenone’s antifibrotic effect alleviates ECM-mediated constraints on small follicle growth, thereby allowing follicles to develop. Furthermore, we identified the stromal collagen–granulosa signaling as an important negative regulator of follicular development,” said Prof. Kawamura, adding, “Therefore, finerenone stimulates follicular development through its antifibrotic action on the ovarian stroma.”
Other drugs such as nintedanib and ruxolitinib also induced follicle formation in mouse ovaries. These drugs prevent fibrosis through a different mechanism from finerenone, which confirmed the collagen-induced constraint hypothesis.
Would these findings hold true in humans? The team enrolled 14 women with POI who were being treated at HKU Shenzhen Hospital for an experimental study.
Participants received oral finerenone for a period of 3 to 7 months. Follicle development was seen in all participants. Seven patients produced mature oocytes that could be used for in-vitro fertilization (IVF).
The quality of oocytes harvested was comparable to that of same-age women without POI undergoing IVF. While further trials are needed, these findings provide early evidence that antifibrotic therapy may enhance follicle activation in some women with POI.
Discussing these encouraging results, Prof. Kawamura concludes, “Further clinical characterization of FDA-approved oral antifibrotic drugs for their abilities in activating small ovarian follicles in patients offers a promising path to repurposing therapies for POI-related infertility.”
If validated in larger trials, antifibrotic therapy could represent a less invasive alternative to current experimental approaches and expand treatment options for women with POI worldwide.
References:
- Antifibrotic drug finerenone restores fertility in premature ovarian insufficiency – (https://www.science.org/doi/10.1126/science.adz4075)
Source-Eurekalert