Around 100–150 women a year in the UK are diagnosed with severe Twin-Twin Transfusion Syndrome before 18 weeks of pregnancy, but cannot be treated because the only available surgery is too risky for such early gestations. The problem is that TTTS—which affects 10–15% of identical twins sharing a placenta—causes abnormal blood vessel connections that let one twin steal blood from the other, leading to premature birth, disability, or death. The standard treatment, fetoscopic laser surgery, requires inserting a 2–4 mm instrument into the womb, which can cause miscarriage, infection, or fluid leakage. For women diagnosed before 18 weeks, the risks outweigh the benefits, leaving their babies with the worst outcomes and no safe option. This project will build a custom ultrasound-guided High Intensity Focused Ultrasound (HIFU) system that can block the abnormal placental blood vessels from outside the body, without cutting into the womb. The team will test it in a clinical study with around 13 women, checking first whether the technique is safe for mother and baby and whether it stops blood flow through the faulty connections. If HIFU works, it could replace the need for risky laser surgery in these early pregnancies and lead to larger trials. The system might later be adapted to treat other pregnancy complications or to block blood vessels feeding tumours.
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Twin-Twin Transfusion Syndrome (TTTS) affects 10-15% of identical twins who share a placenta. This may need treatment that is high risk for around 400-600 babies every year in the UK. In TTTS, blood moves from one twin to the other through abnormal blood vessel connections in the placenta called anastomoses, which directly link the blood supplies of the twins. These anastomoses may cause one twin to get less blood and amniotic fluid and the other twin too much blood and amniotic fluid. TTTS is the biggest cause of premature birth, death or disability in identical twin pregnancies. TTTS can be seen with a specialist ultrasound scan. Women who have severe TTTS have the worst outcomes, and are recommended to have a treatment which can divide the twins' placenta by blocking the abnormal blood vessel connections that cause TTTS. At the moment this is done using a technique called fetoscopic laser, a surgical procedure where a 2-4 mm wide instrument is placed into the womb so it can reach the placenta. As the laser must be put inside the womb, this treatment is risky and can cause miscarriage, bleeding or infection in the womb, or leakage of fluid from the womb which can affect the twins' development. This is why fetoscopic laser is only used in serious cases; the risks are too high to for it to be used in cases that are not as serious. In the UK about 100-150 women per year have severe TTTS diagnosed before 18 weeks. Even though they need treatment, fetoscopic laser cannot be used because the risks are too high and instruments too big. This is a group of women whose babies have the worst outcomes of all those diagnosed with TTTS, but we have no good, safe treatments for them. Our research group works with High Intensity Focused Ultrasound (HIFU), which uses very powerful ultrasound waves that can block blood vessels in the placenta without needing to make a hole in the womb. As HIFU does not require invasive surgery to be done, we could use it to treat severe TTTS in pregnancies below 18 weeks. So far, we have tested this treatment in pregnant sheep, which share similarities to human pregnancies. Based on these experiments HIFU seems to be work well and is a safe way to block placental blood vessels. At Queen Charlotte's and Chelsea Hospital, London, we will work with experts in HIFU from the Institute of Cancer Research, London, international fetal medicine experts, pregnancy support groups and patient volunteers with experience of TTTS to design a clinical study. We will offer around 13 women and babies diagnosed with TTTS before 18 weeks the HIFU treatment as part of a carefully designed study. In this very early stage study look primarily at whether the technique is safe for mothers and babies and if we can stop blood flowing through the abnormal vessels connecting the two halves of the placenta. If HIFU is safe and effective, it would prevent the need for riskier laser treatment when these pregnancies reach 18 weeks and will most likely lead on to further, larger clinical trials. As part of this study, we will build a special ultrasound guided HIFU system that combines the best available ultrasound imaging of the babies and placental blood vessels with a HIFU system specially designed to direct the treatment to exactly the right area in the placenta. We will also design a special computer program to control the whole system. Fixing the abnormal placental blood vessels without harming the mother or the babies is difficult. The experiments we have done in sheep has shown us some of the problems that might happen. There are no places to buy a HIFU system that makes good enough pictures or allows accurate treatment of the abnormal blood vessels. Therefore we need to build a one to use in this study. The HIFU system we build may also be used in the future for treating other problems that can happen in pregnancy or for cancer treatment, where it could block the blood vessels that feed tumours.
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