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Cell atlas of the endometrium in women with PCOS may lead to better treatment

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Women with polycystic ovary syndrome (PCOS) find it harder to get pregnant, have more frequent miscarriages and have a higher risk of developing endometrial cancer. Now, researchers have shown that the uterine lining of these women differs in terms of both the composition of individual cells and gene expression. The results open the door to new drug treatments.

PCOS is the most common hormonal disorder affecting 11 to 13 per cent of women of reproductive age. Women with the syndrome have difficulty getting pregnant and are at increased risk of miscarriage and uterine cancer, especially cancer of the endometrium. It is also common for affected women to be overweight and insulin resistant.

By studying endometrial tissue samples from five healthy women and 12 women with PCOS, the researchers created a cell map of individual cells.

 

The women were all of similar age, weight and BMI and the tissue samples were taken at the same phase of the menstrual cycle to eliminate factors that could influence the analyses. In the study, all women were overweight, but only the women with PCOS were insulin resistant and had elevated levels of male sex hormones.

In total, almost 250,000 cell nuclei from the women’s uterine linings were analysed. The researchers found a clear difference in the composition of cell types with a higher proportion of so-called epithelial cells and a lower proportion of stromal cells in the uteruses of women with PCOS.

“These results show that the growth of the cells is affected, which may explain why it can take longer for affected women to become pregnant and why they are more likely to miscarry, as well as contributing to the increased risk of endometrial cancer,” said Elisabet Stener-Victorin, professor of Reproductive Physiology at Karolinska Institutet and research leader of the current study.

In the detailed cell map, the researchers can show that many genes in specific cell types have a disturbed expression in women with PCOS. A large proportion of the affected genes are linked to difficulties for the early embryo to attach to the uterus, miscarriage and endometrial cancer with functions affecting cell-to-cell attachment and communication.

“Our analyses show that certain cell types in the endometrium have disrupted communication and interaction specific to PCOS,” said Gustaw Eriksson, one of the study’s first authors and a doctoral student in Elisabet Stener-Victorin’s research group.

The study also included a part where the women with PCOS underwent treatment with the diabetes drug metformin with or without lifestyle advice on diet and exercise. After 16 weeks of treatment, the researchers found that many gene expressions in specific cell types, especially in the epithelial and stromal cells, were normalised by metformin, but also by lifestyle changes, although not as pronounced.

“We can show that metformin seems to have many more functions in women with PCOS than lowering blood sugar. In the study, all the women were overweight, but it is likely that metformin has similar effects in affected women who are not overweight but insulin resistant if they have problems getting pregnant or have repeated miscarriages,” said Elisabet Stener-Victorin.

Another important finding was the correlation between gene expression in specific cell types and important clinical features of PCOS, such as elevated levels of male sex hormone and insulin resistance, highlighting the complex relationship between hormonal and metabolic factors and endometrial dysfunction.

“As we identified changes in gene expression in specific cell types, this study provides crucial guidance for developing more targeted treatments for PCOS-related endometrial dysfunction,” said Elisabet Stener-Victorin.

The study is a collaboration with Dr Congru Li as joint first author, and Associate Professor Qiaolin Deng and Associate Professor Sophie Petropoulos with joint senior and corresponding authorship.

The research was funded by the Swedish Research Council, the Novo Nordisk Foundation, the Diabetes Foundation and the Knut and Alice Wallenberg Foundation, among others. The researchers declare that there are no conflicts of interest.

Fertility

Housing, work and fertility stop Britons having the families they want – research

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Housing, work and fertility pressures are stopping many Britons growing the families they want, new research suggests.

A UK fertility report found that 79 per cent of people surveyed who had tried to conceive in the past five years would like more children than they currently have.

Among parents with one child, that figure rises to 88 per cent.

The report surveyed more than 1,000 people across the UK who had tried for a baby in the past five years.

While birth rates continue to fall, the findings suggest it is not because people no longer want children. Instead, many respondents said external pressures are making it harder to grow their families.

The findings, from wellness brand Wild Nutrition’s Fertility Disconnect report, highlight how financial pressures, fertility struggles and gaps in reproductive health knowledge are shaping modern family life in the UK.

Gail Madalena, fertility nutritional therapist at Wild Nutrition, said: “People often assume fertility begins the moment they decide to try [for a baby].

“In reality, egg and sperm health are shaped months and years earlier.

“By the time someone starts thinking about fertility, their body has already been responding to its environment for a long time.”

Among the biggest barriers, 26 per cent said career progression affected their family plans, 25 per cent cited housing affordability and lack of space, and 52 per cent said they required medical intervention during their fertility journey.

The report also found that almost a quarter of respondents had spent more than two years trying to conceive.

Trying for a baby can take a significant toll on mental health and relationships, especially for those navigating fertility treatment.

According to the research, 38 per cent of respondents said trying to conceive had negatively affected their mental health. That figure rose to 99 per cent among people undergoing fertility treatment.

Julianne Boutaleb is a perinatal psychologist.

She said: “Navigating a fertility journey is about so much more than medical appointments and procedures.

“It’s an emotional marathon that can take a huge toll on your mental wellbeing.

“Sadly, the stats show that 15 per cent of couples going through fertility treatment say their relationship has been irrevocably impaired.”

The report also highlighted the realities of secondary infertility, which affects around one in 20 people, challenging the assumption that having one child means conceiving again will be straightforward.

Researchers found many people felt under-informed about fertility, particularly younger adults.

Ten per cent of Gen Z respondents said they “know nothing” about fertility, while only one in five respondents said they know “a lot” about egg health.

The report also found that 60 per cent of women were unaware of fertility testing options, and one in five Gen Z respondents said they felt uncomfortable discussing fertility, even with their partner.

Around 40 per cent of those surveyed supported fertility education being included in schools, covering topics such as egg health, sperm health and hormonal health.

The report also explored how lifestyle and long-term health may influence fertility outcomes.

Many respondents said they only made changes once they started trying to conceive.

Some 44 per cent improved their diet when trying for a baby, while 32 per cent reduced alcohol intake at that stage.

The report also referenced emerging research that suggests ultra-processed foods and microplastics could have an impact on reproductive health.

While fertility conversations often focus on women, the findings showed male fertility issues are also affecting many families.

Seventeen per cent of respondents cited sperm health issues as a barrier to conception, while male factors contribute to around half of all fertility challenges.

Only one in four men said they would share fertility struggles with friends.

“Many causes of male infertility are entirely treatable yet so often the last resort is the first response,” said Ian Stones, co-founder at Test Him Ltd.

The findings come as UK birth rates remain below replacement level.

The report noted that the UK fertility rate is now 1.41, meaning that on average women give birth to 1.41 children over their lifetimes. The replacement rate, or rate that maintains population numbers, is 2.1.

It also said the average age of mothers has risen to 31, while birth rates are falling across most age groups except among over-40s.

“There is no single fertility story, and it is rarely a simple, linear narrative,” said Dr Zeynep Gurtin, lecturer in women’s health at UCL.

Dr Gurtin added that better fertility education, fairer access to treatment and more open conversations around infertility and pregnancy loss are needed.

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Femtech World reveals fertility innovation award shortlist

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Femtech World is thrilled to reveal the shortlist for the Fertility Innovation Award.

The award, sponsored by FinDBest IVF, celebrates a pioneering product, service or initiative that is transforming fertility care and support.

FinDBest IVF is a global B2B digital platform created to simplify and accelerate how IVF and ART manufacturers connect with trusted, pre-vetted distributors around the world.

This year’s nominees represent a remarkable breadth of approaches to fertility care: from clinic-floor breakthroughs to at-home hormone intelligence to truly borderless access.

Three companies made the cut, with each tackling a real, persistent barrier in reproductive health.

Congratulations to the shortlist and many thanks to everyone who entered.

Fertility Innovation Award Shortlist

 

HRC Fertility’s Needle-Free IVF is a pioneering advancement designed to transform one of the most challenging aspects of fertility treatment: daily hormone injections.

Developed by board-certified reproductive endocrinologist Dr Rachel Mandelbaum, this innovative approach reimagines how stimulation medications are delivered during IVF and egg freezing, dramatically improving the patient experience while maintaining the same trusted clinical outcomes.

Inspired by feedback from patients who struggled with the injection process, Dr Mandelbaum adapted an innovative drug-delivery system commonly used in other areas of medicine and applied it to reproductive care

Mira is a hormonal health technology company that provides lab-grade hormone testing and AI-driven insights to help women and couples understand their fertility. 

The platform has already supported more than 200,000 couples on their fertility journeys worldwide, helping over 60,000+ users achieve pregnancy.

For some users, pregnancy rates have reached up to 89 per cent within six months, demonstrating how accurate hormone data can significantly improve fertility outcomes.

 

Founded in 2021 by Marija Skujina, a Certified Fertility Nurse Specialist accredited by the European Society of Human Reproduction and Embryology, with nearly 15 years of clinical experience at one of the world’s top IVF clinics, and having navigated her own fertility journey as a patient, Marija built the clinic she had always wished existed.

Plan Your Baby began with a bold, but simple mission – make best quality fertility and pregnancy available anywhere.

Plan Your Baby has created a new generation fertility and pregnancy clinic with patients accessing expert consultations remotely, while blood tests and ultrasound scans are available at over 450 locations across the UK, eliminating the exhausting travel burden that often forces people to take days off work, relocate appointments, or abandon treatment altogether

What happens now

The shortlist will be judged by a representative from category sponsor FindBestIVF, with the winner announced at a virtual event on June 19.

Winners will receive a trophy and be interviewed by a Femtech World journalist.

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First patients dosed in miscarriage trial

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The first patients have been dosed in a UK miscarriage trial testing a new intravaginal drug delivery platform for threatened miscarriage.

The FREEDOM study is evaluating 400mg progesterone Callavid in patients diagnosed with luteal phase insufficiency, a condition in which progesterone levels may be too low to support early pregnancy, increasing the risk of infertility and recurrent miscarriage.

Callavid uses a patented leak-free, tampon-like design intended to address the limitations of current vaginal treatments, which rely on self-administered pessaries, or vaginal suppositories, that can leak and may move during use.

The device is being developed by London-based Calla Lily Clinical Care, a medical technology company focused on women’s health. The trial is funded by the National Institute for Health and Care Research and run in collaboration with the Trial Management Unit at University Hospitals Coventry and Warwickshire NHS Trust.

According to the company, Callavid is positioned to become the world’s first drug-device combination product to support treatment of threatened miscarriage, as well as luteal phase support as part of assisted reproductive technologies, including in vitro fertilisation, or IVF.

The Government’s Renewed Women’s Health Strategy for England cites estimates ranging from 120,000 to 250,000 cases of miscarriage a year in the UK. Administering 400mg micronised progesterone twice daily is recommended by the National Institute for Health and Care Excellence for women who have suffered a previous miscarriage and experience bleeding during early pregnancy, known clinically as threatened miscarriage.

Current pessary delivery methods can result in uncertain placement and movement during use. These limitations can reduce the efficiency and consistency of drug absorption, potentially compromising delivery of the intended dose, and patients are regularly advised to lie horizontal for extended periods after each administration.

The FREEDOM trial is led by professor Siobhan Quenby MBE, an authority on miscarriage and preterm birth, and an honorary consultant at University Hospitals Coventry and Warwickshire NHS Trust. The study aims to evaluate safety, user acceptability and progesterone absorption, with the goal of providing evidence of improved usability in self-administration.

Quenby commented: “Through my clinical practice, I see the difficulties patients face with existing vaginal progesterone products at an already very stressful time. Callavid offers a promising new solution to ensure delivery of the correct progesterone dosage and give women greater confidence in their treatment. There is genuine excitement among both clinicians and patients at the prospect of Callavid progressing into clinical trials.”

Dr Lara Zibners, co-founder and chair of Calla Lily Clinical Care, added: “As a physician and entrepreneur, I believe we have a responsibility to create more effective, patient-centred solutions in women’s health. Having been through seven rounds of IVF myself, I have experienced how difficult progesterone treatment can be, and I am proud to be advancing an innovation shaped by both medical insight and lived experience.”

Thang Vo-Ta, co-founder and chief executive of Calla Lily Clinical Care, said: “Dosing the first patients in the FREEDOM study marks a critical milestone for Calla Lily Clinical Care. Callavid represents a differentiated delivery modality for a broad range of therapeutics in the pharma pipeline, and will create new opportunities to extend the lifecycle of existing drugs. This trial is a key step in demonstrating Callavid’s massive potential.”

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