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.

LOS ANGELES (AP) — Los Angeles Mayor Karen Bass is heading into a challenging reelection bid as she continues to suffer fallout from last year’s devastating wildfire and ongoing criticism of City Hall on issues from street paving to homelessness.

The deadline is Saturday for candidates to enter the contest ahead of the June 2 primary election. Bass — a first-term Democrat and the first Black woman to hold the post — already is facing challenges from tech entrepreneur and nonprofit founder Adam Miller; reality television personality Spencer Pratt, who lost his home to the deadly Palisades Fire; and community organizer Rae Huang. A late entry was city council member Nithya Raman, a onetime Bass supporter who will now be trying to oust her.

Although the contest is officially nonpartisan, it is breaking along sharp political lines.

Pratt is a Republican in a heavily Democratic city who was endorsed by Steve Hilton, a Republican candidate for governor, and Richard Grenell, an ally of President Donald Trump. Raman was the first council member elected with the backing of the Democratic Socialists of America. Huang has positioned herself to the political left of Bass, who while in the U.S. House was a member of the Congressional Progressive Caucus.

Bass greeted Raman to the race with a pointed jab: “The last thing Los Angeles needs is a politician who opposed cleaning up homeless encampments and efforts to make our city safer,” Bass campaign adviser Douglas Herman said in a statement.

The race is unfolding at an unsettled time for the city of nearly 4 million.

Complaints about the cost of living — whether for rent, taxes or groceries — are a constant refrain. Dirty, pocked streets and sidewalks abound. Hollywood jobs have been decamping for years for more affordable locales.

Ongoing Trump administration immigration raids have shaken the city. Despite studies showing a slight decline in the homeless population, encampments remain commonplace. And recovery from the Palisades Fire, which killed 12 people and destroyed much of the tony seaside neighborhood in January 2025, continues at a pace that some say is too slow.

In an upbeat speech this month laying out her vision for the city's future, Bass talked of the upcoming 2028 Olympics in the city and plans to spruce up busy thoroughfares.

“Even in this difficult chapter in our history, great events, moments of unity, are possible,” Bass said. “And they are coming.”

Los Angeles-based Democratic consultant Bill Carrick sees the race as wide-open. Under California's primary rules, all candidates appear on the same ballot and the top two finishers advance to the November general election — a system that can lead to unpredictable outcomes. A candidate can win the mayoralty outright by capturing more than 50% of the primary vote, but that appears unlikely with a large field that is also expected to include a string of little-known contenders.

Voters are “kind of unhappy with city government, and I think the Palisades Fire certainly contributed enormously with that feeling,” Carrick said.

The mayor, who was on a trip to Ghana as part of a presidential delegation when the fire began raging through the Palisades neighborhood, has been on the defensive for her actions during and after the blaze.

The Los Angeles Times has published a series of reports, based on public records requests, showing that drafts of the Los Angeles Fire Department’s after-action report included deletions and revisions intended to soften the failures of city and department officials.

This week Bass’ office forcefully denied allegations in a Times story, based on anonymous, secondhand sources, that she pushed for changes in the report before publication to shield City Hall from potential legal action. She told reporters that the account was “completely fabricated.”

Officials have said the deadly blaze was ignited by remnants of a Jan. 1 fire that continued to smolder underground. In October, a 29-year-old man was arrested and charged with sparking the earlier fire. The LAFD has faced scrutiny over whether it properly extinguished the New Year’s Day blaze.

On his website, Pratt — who rose to reality-TV fame alongside his wife, Heidi Montag, on “The Hills” — said he watched his home burn “because the system failed us.”

“We don’t need more government programs,” Pratt added. “We need common sense, accountability, and a mayor that shows up for everyone.”

Miller, a Democrat running as an outsider with the ability to invest in his own campaign, poses a new challenge for Bass, who defeated billionaire Rick Caruso in her 2022 election. Miller founded Cornerstone OnDemand, a global education company, and later cofounded the Better Angels nonprofit to address homelessness.

“Los Angeles has extraordinary potential but too often City Hall hasn’t been there for the people who call it home,” Miller said in a statement.

Bass also avoided two potential strong opponents in the contest.

Caruso decided not to run again after months of equivocation, and Los Angeles County Supervisor Lindsey Horvath announced late Friday that she, too, would not enter the race. Both have been outspoken critics of the mayor's handling of homelessness and the fire and were widely seen as possible contenders.

“It's clear you want a different kind of leadership and you are ready to see change in your city,” Horvath said in a video posted on the social platform X, but she added that her work on the county board was not finished.

FILE - A firefighter battles the Palisades Fire in Mandeville Canyon, Jan. 11, 2025, in Los Angeles. (AP Photo/Jae C. Hong, File)

FILE - Mayor Karen Bass speaks at a vigil, June 10, 2025, in Los Angeles. (AP Photo/Eric Thayer, File)