HKUMed and HKU Shenzhen Hospital achieve breakthrough in treating premature ovarian insufficiency with drugs to activate dormant eggs and restore fertility

A research team from 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.

HKUMed reveals that using drugs to treat POI by awakening dormant eggs and facilitating their development into usable antral follicles, is a key breakthrough in restoring fertility (from left: Professor William Yeung Shu-biu, Professor Ernest Ng Hung-yu and Dr Wang Tianren). Photo source: HKUMed

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.

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

There may still be a small number of small dormant follicles in the ovaries of patients with POI. However, they cannot develop naturally into the antral follicle stage, which is essential for ovulation and fertility treatments. Professor Liu Kui from the Department of Obstetrics and Gynaecology at the School of Clinical Medicine of HKUMed, who led the research, said, 'These small follicles represent a source of potential eggs. The key is finding a way to awaken them and help them develop into usable antral 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.

Professor Ernest Ng Hung-yu, Clinical Professor in the Department of Obstetrics and Gynaecology at the School of Clinical Medicine, HKUMed, explained, 'Patients with POI often experience fibrosis, characterised by an excessive deposition of collagen in the ovarian microenvironment, which severely limits follicle growth and ultimately leads to infertility. We found that finerenone effectively reduces fibrosis, creating a favourable microenvironment for the continuous development of follicles into mature antral follicles.'

Professor Ernest Ng Hung-yu remarks that patients with POI often experience fibrosis in the ovarian microenvironment, which severely limits follicle growth and leads to infertility. However, finerenone effectively reduces fibrosis, creating a favourable microenvironment for the continuous development of follicles into mature antral follicles. Photo source: HKUMed

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

This study also revealed the underlying pathological mechanism of follicular development arrest in POI. The team found that ovarian fibrosis is not caused solely by ageing. It is also a key factor leading to the stagnation of follicular development. To verify this, the team tested multiple antifibrotic drugs with different targets to redefine the initiation and growth mechanism of primordial follicles from the perspective of the 'ovarian microenvironment'. They proposed a new treatment framework for POI based on these findings. In addition, the study confirmed that other FDA-approved antifibrotic drugs, such as Nintedanib and Ruxolitinib, had similar effects in promoting follicular development in preclinical studies. This suggests that treatments targeting the ovarian microenvironment, rather than just the follicles, may have potential in broader clinical application.

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.'

Professor Liu Kui (middle, front row) from the Department of Obstetrics and Gynaecology at the School of Clinical Medicine, HKUMed, who led the research team, states that improving the ovarian microenvironment, especially by addressing fibrosis, is important for treating POI-related infertility. Photo source: HKUMed

About the research team

The study was led by Professor Liu Kui from the Department of Obstetrics and Gynaecology at the School of Clinical Medicine, HKUMed. The research team includes Professor Ernest Ng Hung-yu, Clinical Professor, Professor William Yeung Shu-biu, Emeritus Professor, Dr Wang Tianren, Clinical Assistant Professor, and PhD student Lin Zexiong, from the same department; as well as Dr Li Yu, Chief of Service, and Dr Li Yuan, postdoctoral fellow, from the Reproductive and Prenatal Diagnostic Medicine Centre at HKU-SZH.

Acknowledgements

This study was conducted in collaboration with HKU-SZH, which served as a clinical research partner. It received funding support from the Shenzhen Science and Technology Innovation Committee.

Kentucky Gov. Andy Beshear is directly asking Sen. Mitch McConnell, the state's most powerful figure in Congress, to disclose more about his condition after three weeks of silence from the 84-year-old since he was hospitalized in Washington.

The letter released Wednesday from Beshear, a Democrat who is considered a potential presidential candidate in 2028, to the former Senate Republican leader says, “Kentuckians have grown increasingly concerned about the current state of your health and well-being, and ability to hold office.”

McConnell, whose physical condition has visibly declined in recent years, was hospitalized June 14. He has not released a public statement, photos or videos since. Aides have disclosed nothing specific about his condition, other than to say last week that McConnell “continues to improve, and is working closely with his staff on Kentucky and Senate matters while the Senate is out of session.”

That lack of detail has fueled rampant speculation about his prognosis and whether he will return to the Senate when it reconvenes next week. The firestorm was enough that Republican Senate leaders, including Senate Majority Leader John Thune, R-S.D. and Wyoming Sen. John Barrasso, on Tuesday made public statements saying they had talked to McConnell and he was alert and discussing current events.

Speaking to reporters aboard Air Force One on Wednesday evening, as he returned home following the NATO summit in Turkey, Trump was asked about McConnell but said the pair had not spoken.

“I have no idea how he’s doing," Trump said.

McConnell is retiring at the end of his term in January, and the campaign to elect his successor already is underway. Kentucky’s Senate succession law, which Republican legislators have twice changed during Beshear’s tenure, does not give the governor a role in picking a temporary successor should McConnell’s seat become vacant before his term ends.

Under the latest change in 2024, Beshear would call a special election if the seat became vacant. The winner of that election could take office after the result is certified. The general election winner would be sworn in as part of the new Congress in January. But there are unresolved questions about the timing of a special election under the untested law and the possibility the seat could remain vacant until January.

Beshear ended the letter by wishing McConnell “a safe and speedy recovery.”

A look at what an absence from the Senate or a vacancy could mean.

There is not much, if anything, that Beshear, Kentucky lawmakers or the Senate could do if McConnell remains in office but is unable to perform his duties between now and when the current Congress expires in January.

Senate rules do not allow proxy voting. But there have been extended Senate absences before, and the chamber has continued its business with however many senators are in attendance. Republicans currently hold a 53-47 advantage. Without McConnell, that means a maximum of 52 Republican votes are available.

McConnell had been among the senators blocking war powers resolutions that seek to limit President Donald Trump's military options in Iran. Without him, the administration has less of a buffer. On the other hand, McConnell already had been among the Republicans refusing to support Trump's sweeping elections law overhaul.

The 17th Amendment to the U.S. Constitution calls for Senate vacancies to be filled by popular elections. But it allows state legislatures to empower governors to appoint an interim senator to serve through those campaigns. Most states have taken this option, according to the Congressional Research Service.

Kentucky law allowed interim appointments until 2021, when McConnell and other state GOP leaders persuaded the Republican-run Legislature to make a change. They did not want Beshear to shift the partisan balance in Washington if he got the opportunity. They called for a committee of the previous senator's state party to select three people from whom the governor could choose an interim senator. In this case, that would mean Beshear picking which Republican would fill a vacancy. Several states have this system.

Kentucky lawmakers changed the law again in 2024 to require a special election. The only role for the governor is to call that election.

Beshear vetoed the 2021 and 2024 changes but Republican lawmakers overrode him.

The 2024 law says Beshear “shall” issue a proclamation for a special vote but it does not say when he should make that proclamation or what the election date must be. Separate laws require certain minimum windows between a proclamation and the election date, but not necessarily a maximum window.

Some officials have argued that any vacancy after Aug. 3 would mean a special election concurrent with the general. They have even speculated that at some point, it would be impractical to have a special election at all given the regular election already taking place.

The Kentucky secretary of state’s office declined to speculate on a hypothetical time frame.

If a special election was needed, the simplest option would be to hold it at the same time as the regular general election.

For the full Senate term that begins in 2027, Republicans nominated U.S. Rep. Andy Barr and Democrats nominated former state lawmaker Charles Booker. Concurrent elections would be separate, requiring new nominations by the parties, though they could choose Barr and Booker. Regardless, in this scenario voters would be electing the immediate replacement and the full-term lawmaker on the same Election Day.

Multiple vacant House seats have been filled that way with little national attention.

Yes. The 2024 law has never been tested. If a vacancy occurred, there could be different interests between parties and even among Republicans about special election timing and whether to hold one at all. That could create any number of legal questions and disputes that have to be settled by the courts.

Beshear's office did not immediately respond to an inquiry about how he interprets the law.

This story has been corrected to reflect that it depends on what the governor might do to determine whether there might be a special election if there was a Senate vacancy after Aug. 3 and whether the seat might remain vacant until January.

FILE - Sen. Mitch McConnell, R-Ky., arrives for a hearing at the Capitol in Washington, Tuesday, May 19, 2026. (AP Photo/J. Scott Applewhite, File)