Findings from the largest study of its kind, led by University of Warwick and University Hospitals Coventry and Warwickshire (UHCW) NHS Trust with funding from pregnancy charity Tommy's, have revealed an abnormal process in the womb lining as the explanation behind some preventable pregnancy loss that paves the way for new treatments for some women who experience recurrent miscarriage.
Around one in six of all pregnancies are lost, mostly before 12 weeks, and each miscarriage increases the risk of another pregnancy loss. While the impact of embryo quality on miscarriage risk has been extensively studied, the endometrium (the womb lining) has largely remained a missing 'black box' in reproductive medicine.
In a study published today in Science Advances, researchers have uncovered a key piece of the miscarriage puzzle, tracing miscarriage risk back to a problem with the womb lining before pregnancy. This research offers a new scientific explanation as to why some women experience repeated pregnancy loss, even with healthy embryos.
"This is about identifying preventable miscarriages," said lead author Warwick Medical School's Dr Joanne Muter, whose work is funded by Tommy's as part of its National Centre for Miscarriage Research. "Many women are told they've just had 'bad luck', but our findings show that the womb itself may be setting the stage for pregnancy loss, even before conception takes place."
By analysing over 1,500 biopsies from more than 1,300 women, the team found that an essential biological process called the 'decidual reaction', which prepares the womb lining for pregnancy each month, often doesn't progress properly in women with a history of miscarriage.
The endometrium's role is to receive the embryo and support the development of the placenta throughout pregnancy. The decidual reaction transforms the womb lining into a supportive tissue for the embryo to implant. When it doesn't fully activate or becomes dysregulated, it creates an unstable environment that, while still allowing embryos to implant, increases the risk of bleeding and early pregnancy loss.
Crucially, this isn't random. The abnormal response in the womb lining, whether too weak or excessively strong, recurs across menstrual cycles for some women at a rate far greater than chance would predict. This suggests a consistent, measurable, and potentially preventable cause of miscarriage risk.
The research also shows that experiencing one miscarriage significantly makes it more likely that the womb lining will respond abnormally in future cycles, explaining why miscarriage often recurs.
Senior author Professor Jan Brosens, Professor of Obstetrics & Gynaecology at Warwick and UHCW NHS Trust and Scientific Director of the Tommy's National Miscarriage Research Centre said: "It is well-established that chromosomal errors in embryos account for the rise in miscarriage rates in women older than 35 years. This study shows that each miscarriage increases the risk of an embryo implantation in an abnormal womb lining, regardless of age.
"Thus, the frequency of one of two events - abnormal embryo or abnormal decidual reaction - happening over hundreds of menstrual cycles determines the likelihood of miscarriage in each individual woman. Importantly, we now have the tools to screen for the risk of preventable miscarriage and to evaluate treatments that improve the womb lining before pregnancy."
On the back of this research, the team has developed a diagnostic test to measure the molecular signals of a healthy or dysfunctional decidual reaction. The test is being piloted by UHCW NHS Trust at University Hospital, Coventry and has already supported the care of more than 1,000 patients.
Dr Jyotsna Vohra, Director of Research, Programmes and Impact at Tommy's, said: "Far too often, women and birthing people who experience the trauma and devastation of recurrent miscarriage are left without answers.
"These findings from Tommy's National Centre for Miscarriage Research pave the way not only for an explanation in some cases but more importantly for treatments that could prevent future pregnancy losses."
One of the patients offered the new test, Holly Milikouris, says being given the opportunity to take part in the trial was life changing after she had experienced five miscarriages.
Holly's diagnostic test revealed that her womb lining prepared poorly for pregnancy which had affected the development of her embryos. After undergoing treatment by Professor Brosens, she and her husband Chris went on to have two healthy children, three-year-old George and 17-month-old Heidi.
"My miscarriages were all 'missed', which means there were no symptoms to let us know there was a problem," explained Holly, a civil servant from Cheshire. "We found out when I went for a scan and a grew to dread having scans.
"We felt lost and were beginning to accept that I might never successfully carry a pregnancy. The treatments that typically can help women who have experienced miscarriages hadn't worked for us and each time we tried again we felt like we were rolling a dice with the baby's life.
"Being given the opportunity to take part in this trial was life changing. For the first time the results of my biopsy were normal, and we went on to have not one, but two successful pregnancies. We will never be able to thank Professor Brosens enough and are hopeful that the results of this groundbreaking study will help many other families."
Dr Tajnin Islam, a psychiatrist from Chester, had also experienced several failed pregnancies and felt she was running out of options with conventional methods before finding out about the clinic at University Hospital, Coventry. A test and biopsy carried out by Professor Brosens showed her womb lining also mounted a poor decidual reaction and after treatment she successfully retained a pregnancy.
Tajnin and her husband, a GP, now have a healthy 16-month-old son, Mivaan, who she describes as "a blessing."
"I think this research and treatment is going to help a lot of women out there," she said. "I'm over 40 and if I can have a baby then other women with my condition can also find the reason behind why they are having miscarriages and go on to have a baby. Thank you to Professor Brosens and the team."
Current fertility diagnostics focus heavily on embryos, hormone levels, or genetic factors, often overlooking the role of the womb. This breakthrough positions the womb lining as a key player in early pregnancy health, opening new avenues for pre-conception care, personalised treatment, and emotional relief for patients who have long lived without answers.
