UK Scientists Link Repeated Miscarriages to Defect in Womb Lining, Develop New Diagnostic Test
UK researchers have identified a link between womb lining issues and recurrent miscarriage, leading to a new test that may help detect risks before pregnancy.
Researchers in the UK have identified a malfunction in the womb lining as a significant contributor to recurrent miscarriages—even when embryos are healthy. The new study entitled “Stalling of the Endometrial Decidual Reaction Determines the Recurrence Risk of Miscarriage,” was published June 25 in the journal Science Advances. The scientists’ findings have led to the development of a new diagnostic tool aimed at identifying women at risk before pregnancy begins.
The study, led by scientists at the University of Warwick, sheds light on a poorly understood biological process called the “decidual reaction,” which prepares the endometrium—the inner lining of the uterus—for embryo implantation.
“This is about identifying preventable miscarriages,” said lead author Joanne Muter, PhD of Warwick Medical School in a press release. “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.”
The team analyzed 1,555 biopsies from 1,308 women who sought care at the Implantation Research Clinic at University Hospitals Coventry and Warwickshire (UHCW) NHS Trust. These patients had experienced one or more miscarriages or ongoing fertility issues.
Disrupted Decidual Reaction Creates Unstable Uterine Environment
In many of these women, the researchers observed that the decidual reaction did not activate or progress as it should. This disruption results in an unstable uterine environment that still allows embryos to implant but increases the likelihood of early pregnancy loss.
Senior author Jan Brosens, PhD, Professor of Obstetrics & Gynaecology at Warwick and UHCW NHS Trust and Scientific Director of the Tommy’s National Miscarriage Research Centre noted in the press release, “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, regardless of age.”
“… we now have the tools to screen for the risk of preventable miscarriage and to evaluate treatments that improve the womb lining before pregnancy,” said Senior Author Professor Jan Brosens. (Photo credit: University of Warwick)
“The endometrium’s role is to receive the embryo and support the development of the placenta throughout pregnancy,” the researchers explained in the release. “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.”
New Test Measures Womb Readiness and Immune Cell Activity
To detect these abnormalities, the research team developed the Digital Endometrium Function Test—abbreviated as (d)EFT—which is currently undergoing a large-scale pilot trial at UHCW. According to the university, more than 1,000 patients have already received the test as part of their clinical care.
The (d)EFT test requires a small biopsy of the womb lining, according to the Warwick Medical School website. In addition, patients provide a blood sample—used to measure progesterone level—and undergo a transvaginal ultrasound scan. They must also use an ovulation test or wearable device to determine their peak fertility day.
The test evaluates three key markers:
- Endometrial readiness: Digital PCR technology measures biomarkers that indicate whether the endometrium can support embryo implantation.
- Timing of implantation window: PCR results combined with mathematical modeling determine when the womb lining is most receptive.
- uNK cell levels: Digital image analysis measures uterine natural killer cells, which, in abnormal numbers, are linked to IVF failure or increased miscarriage risk.
“High uNK cells are linked to implantation and IVF failure, whereas low levels of uNK cells may increase the risk of miscarriage,” according to the Warwick Medical School website.
The research, funded by UK pregnancy charity Tommy’s, has the potential to shift how clinicians assess and treat miscarriage risk. Current diagnostics often focus on embryo quality, hormone levels, or genetic issues—overlooking the role of the uterine environment.
By offering a more targeted, womb-centered approach, the researchers hope their work will lead to effective new treatments for the estimated 15% of pregnancies that end in miscarriage.
—Stephen Beale
