Recurrent Pregnancy Loss

Research into RPL, addressing unmet needs of patients and enhancing advocacy

Miscarriage is the most prevalent disorder of pregnancy, with multiple consecutive losses – known as recurrent pregnancy loss (RPL) – having limited effective interventions and increasing the risk posed to a subsequent pregnancy. To better diagnose and treat the condition, Professors Brosens and Quenby in Warwick Medical School identified a pregnancy ‘implantation checkpoint’, with irregular changes to womb-lining cells playing an important role in RPL. Using this knowledge, the pair have led the Implantation and Recurrent Miscarriage Research Clinics since 2012. By 2020 these clinics provided care to over 3,500 patients of multiple miscarriages in the UK and internationally, with 2,000 babies born as a result. Brosens and Quenby had an integral role in establishing Tommy's National Miscarriage Research Centre. Tommy’s is the UK’s leading charity for premature birth, stillbirth and miscarriage. This collaboration with Tommy’s has facilitated and funded research and patient advocacy.

The challenge

In England and Wales miscarriage affects over 200,000 women every year, occurring in around one in six pregnancies. The underlying causes of recurrent pregnancy loss (RPL) were previously poorly understood, with the disorder increasing the chances of future miscarriage with subsequent losses. To increase live birth rates for thousands of women, Professors Brosens and Quenby set out to explore and address this unrecognised and unmet clinical need.

Our approach

Through a combined programme of pathological mechanistic and clinical research at the University of Warwick, processes and cells which regulate womb-lining response to conception were identified. Key findings enabled new strategies for the prediction and prevention of RPL:

• Discovery of an implantation checkpoint, which limits maternal investment in abnormal but highly invasive embryos

• Identification of novel mechanisms controlling embryo implantation in the womb lining (or endometrium)

• UNK test has been developed so that patients receive results in a consistant and rapid manner to aid the treatment plans. Research using samples from the uNK test, discovered a stem cell deficiency in women with RPL.

• A double blind randomised controlled trial of sigalipitn demonstrated that this increased pre-conceptual endometrial stem cells.

• A test for chronic endometritis has been developed and is the basis of a large randomised controlled trial.

• Significant recruitment and involvement in trials of progestogen found a role for this in miscarriage prevention.

Our impact

Under the leadership of Professors Brosens and Quenby, the Implantation and Recurrent Miscarriage Research Clinics provide a research-led service for women with complex reproductive histories. Set up in collaboration with the University Hospital Coventry and Warwickshire NHS Trust, the Clinics have provided care to patients from across the globe, with 2,000 babies born as a result. The Centre has been instrumental in breaking the silence, stigma and lack of information around miscarriage, providing 24,000 women access to treatment through its four associated clinics. The Tommy’s 2019 ‘Tell Me Why?’ video, created based on Warwick research, has been viewed over 16,000 times and helps explain possible causes of recurrent miscarriage. Quenby led the Lancet series Miscarriage Matters published in 2021, which reflected the over 120,000 signature petition lead by Tommy’s requesting improvements in recurrent miscarriage care. The Lancet series was covered by written, audio, television and social media across the World. These activities led to a parliamentary debate in which the Minister endorsed the Lancet recommendations and committed to facilitating their implementation. These recommendations included, national recording and reporting of miscarriages, access to mental health services for those suffering miscarriage and 24/7 miscarriage services be made available to all as part of the women’s health strategy for England.]

Meet the Researcher: Siobhan Quenby

Watch the video below to learn more about Professor Quenby and hear first-hand about her work.

Access UK Parliament 'Miscarriage Research: The Lancet'

See Tommy's website

Lancet Journals Series