An experimental non-invasive procedure which uses high energy soundwaves is safe and could potentially treat a serious pregnancy condition called twin-twin transfusion syndrome (TTTS), according to an early-stage research trial involving UK and European patients.
Led by Imperial College London and Imperial College Healthcare NHS Trust, this world-first study found that high intensity focused ultrasound (HIFU) can safely stop blood flow in the abnormal placental vessels that cause the condition.
While the research suggests that HIFU could be an effective treatment, the researchers have not yet established whether it can stabilise or reverse TTTS. The team is now planning a larger study to assess this. If successful, this treatment could in the future be offered to patients with the condition.
Led by Professor Christoph Lees and published in the American Journal of Obstetrics and Gynecology, this is the first-in-human study of its type in early onset TTTS and involved 10 women from the UK and Europe. The procedure has been attempted in other related complications in identical twin pregnancies where the babies share a placenta. A team from The Institute of Cancer Research in London designed and built the HIFU device used in this study.
TTTS affects between 10 and 15 per cent of identical twins that share a placenta - that's between 300 and 400 pregnancies each year in the UK. Blood flow between the babies is unbalanced, resulting in one twin receiving too much blood and the other receiving too little. This can harm both babies, even causing organ failure for both twins if left untreated. In the most serious cases, one or both babies can die.
Right now, the best treatment for TTTS involves inserting a fetoscope (a small telescope like device) into the womb and amniotic fluid surrounding the twins before using a laser to block blood flow in the shared blood vessels on the placenta's surface. While the laser procedure is often successful, it can cause complications leading to miscarriage.
Professor Christoph Lees, head of fetal medicine at Imperial College Healthcare NHS Trust and professor of obstetrics at Imperial College London, said: "This is very promising research, confirming for the first time that this non-invasive procedure can be used safely in twin-twin transfusion syndrome. That's really encouraging, because at present we are only able to treat this condition by using a more invasive method which has its own risks.
"We hope to follow this study with a bigger clinical trial with 50 to 100 women, so we can determine if it can successfully treat TTTS and understand whether this procedure could be a less risky and equally or more effective option for women and their twin babies.
"This study is the culmination of over 15 years of collaboration. I want to thank all the women and families for trusting us and taking part in our research, as well as the hospitals and centres who referred them to us. Research to find new treatments for TTTS is only possible with their help."
In this feasibility study, the team investigated whether non-invasive, ultrasound-guided high intensity focused ultrasound (HIFU) is a viable and safe treatment between 12 and 17 weeks of pregnancy.
They used a type of ultrasound called Doppler to identify the tiny blood vessels in the placenta which connect the twins' circulations, and which cause TTTS.
A beam of high energy sound waves, generated using a device outside the body, was then used to precisely heat the blood vessels and block blood flow through them. This allows the blood flow between the two babies to become rebalanced.
This new study found the procedure successfully blocked blood flow in 90 per cent of the placental blood vessels treated. Those women taking part, and their unborn twins, experienced no adverse side effects. The treatment was received positively by women taking part. However, as this study was not designed to test real world clinical efficacy in treating early onset TTTS which is a very risky condition, half of the women required further treatment, including laser ablation and sadly some babies did not survive.
While the study could not formally confirm how effective the HIFU procedure was, it showed that HIFU could successfully block blood flow in women with early onset twin-twin transfusion, without adverse side effects.
Patient story
Brioney Garrett, who lives in Cornwall, discovered she had advanced twin-to-twin transfusion syndrome at her 12-week scan in 2022. After learning that laser treatment wouldn't be an option, Brioney was referred to Queen Charlotte's and Chelsea Hospital where she decided to take part in the HIFU research trial. After successful treatment, she went on to give birth to her twin daughters Margo and Nancy later that year. The twins are now almost four and are about to start primary school.
Brioney said: "It was such a tough time for us, being diagnosed with such an advanced form of TTTS. We had such limited options with laser treatment not possible and were facing the very real prospect of losing one of my babies. I feel so blessed that our consultant knew about the research trial and was able to put us in touch with the team at Queen Charlotte's and Chelsea Hospital. This gave us some much-needed hope and, with minimum risk, we jumped at the chance.
"The procedure itself took about 15 minutes, with a few follow-up scans over the next few weeks. It was such a relief to find out that the treatment had worked a couple of weeks later and that both twins were OK. There were a couple of wider complications in the pregnancy related to the syndrome itself. But otherwise the pregnancy progressed well. My daughters Margo and Nancy are thriving now and are about to start primary school.
"I'm so grateful to the hospital team and to everyone involved in the research. They saved my girls' lives. It really means the world to me to have been part of the trial – not just for my family but for other women and babies who may be able to benefit from this in the future."
Dr Adam Babbs, Associate Director of Translational Research at UKRI MRC, said: "Twin-to-twin transfusion syndrome is a life‑threatening condition with very limited treatment options early in pregnancy. This study provides important proof of concept that high intensity focused ultrasound (HIFU) could offer a non-invasive way to intervene earlier, with the potential to improve outcomes for affected babies.
"Through the Developmental Pathway Funding Scheme (now MRC Proof of Concept), MRC supports researchers to de-risk innovative healthcare technologies and progress them towards patient benefit. This project highlights the value of strong collaboration between academic researchers and industry partners and demonstrates how MRC investment is driving forward promising translational research with the potential to make a real difference to patients."
Professor Gail ter Haar, Professor of Therapeutic Ultrasound at The Institute of Cancer Research (ICR) in London, said: "It is extremely rewarding to see high-intensity focused ultrasound reaching this stage of clinical development for the serious condition, twin-twin transfusion syndrome. This is the result of many years of research and collaboration.
"At the ICR, we study how high intensity focused ultrasound (HIFU) interacts with tissue – and we demonstrated that it can reliably and precisely destroy problematic regions, while minimising damage to surrounding healthy structures. High levels of ultrasound heat tissue, so we can essentially cook the cells – and with the focused intensity, we can do this very specifically to the cells and structures of interest, including blood vessels.
"Over many years, we have developed the technology to allow it to move safely into use in patients, designing the clinical protocols that have led us to this point today. I look forward to seeing the results of the larger trials, which will determine whether this technique can provide an equally, or even more effective, option than the current invasive procedure to treat TTTS."
Professor Lees and his team were awarded a £2.2 million grant by the Medical Research Council (MRC) in 2017 to carry out this first-in-human trial of the ultrasound-guided HIFU technology. The team also received funding from The Wiseman Trust and the UK Focused Ultrasound Foundation. Canon Medical Systems is the study's commercial partner.
The team were also supported by patient support groups linked to the Twin-Twin Transfusion Foundation in the US, Multiple Births Foundation (now the Elizabeth Bryan Multiple Births Centre (EBMBC)) and Twins Trust in the UK.
Researchers from the University of Cambridge and also the Centre of Trials Research, funded by the Welsh Government through Health and Care Research Wales and hosted by Cardiff University, also contributed to this research.
Professor Lees is supported by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, a translational research partnership between Imperial College Healthcare NHS Trust and Imperial College London.
