A research team from The University of Hong Kong-Shenzhen Hospital Reproductive Medicine and Prenatal Diagnosis Center/ the Department of Obstetrics and Gynaecology at the School of Clinical Medicine, LKS Faculty of Medicine, the University of Hong Kong (HKUMed), has made a major breakthrough in treating premature ovarian insufficiency (POI). The team discovered that finerenone, a drug used to treat type 2 diabetes-related chronic kidney disease, can promote the development of follicles into mature eggs and form viable embryos in patients with POI. In contrast to traditional strategies focusing solely on direct follicle stimulation, this pioneering study is the first to focus on improving the ovarian microenvironment to treat infertility caused by POI.

A related clinical trial conducted at the University of Hong Kong-Shenzhen Hospital (HKU-SZH) confirmed that the participants experienced significant improvement in follicle development. About half of the participants successfully produced mature eggs, several of which developed into viable embryos. The results confirmed that this ground-breaking approach can restore fertility for women affected by POI. The research findings were published in the prestigious scientific journal Science [link to the publication].

POI affects approximately 1-3% of women of childbearing age worldwide. These patients have difficulty conceiving because of lack of ovarian follicular development. Under normal circumstances, small ovarian follicles develop gradually into larger antral follicles, which respond to ovarian stimulation drugs, enabling ovulation and in vitro fertilisation (IVF) treatment. However, patients with POI often lack antral follicles that can be detected by ultrasound, rendering conventional IVF treatment almost impossible.

A new strategy to improve the ovarian microenvironment to awaken dormant small follicles

The research team adopted the ‘drug repurposing’ strategy to explore novel treatment for POI-related infertility using drugs that have been approved and backed by established clinical safety data. Professor Liu noted that this method can avoid the lengthy and costly process involved in developing new drugs from scratch and can significantly accelerate the translation of the new treatment for clinical use. Leveraging the previous in-depth research into the regulatory mechanism of ovarian follicle development, the team established a systematic screening platform and selected finerenone, a non-steroidal antifibrotic drug from a library of over a thousand drugs approved by the US Food and Drug Administration (FDA). The team found that finerenone has potential clinical value in improving the ovarian microenvironment and facilitating the development of small dormant follicles.

The research team launched a clinical trial at HKU-SZH in 2024, providing pulsed oral therapy to 14 women of childbearing age diagnosed with POI. The therapy was combined with personalised ovarian stimulation regimens for up to seven months. Dr Wang Tianren, Clinical Assistant Professor from the same Department, said, ‘Preliminary results showed that eight participants successfully developed antral follicles that progressed to mature follicles. About half of the participants obtained mature eggs. Three participants developed usable embryos, and another three opted to freeze their oocytes. The treatment results were highly encouraging.’

Ovarian fibrosis is a cause of follicular development arrest

Professor Liu Kui stated, ‘In the past, treatments for POI-related infertility focused mainly on directly stimulating the follicles, but the overall efficacy was limited. Our study is the first to show that improving the ovarian microenvironment, especially by addressing fibrosis, is a key breakthrough in restoring fertility.’