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Children born through IVF face higher risk of cardiovascular disease, warns study

Findings warrant large scale trials to pin down whether risks are a result of IVF techniques or traits found in couples requiring assisted reproduction

Alex Matthews-King

Health Correspondent

Monday 03 September 2018 19:24 BST

The storage and manipulation of egg, sperm and embryo appears to be responsible for increased disease risks in mice studies, and may now hold true in humans

Children conceived through IVF and other forms of assisted reproduction are more likely to suffer from cardiovascular diseases which can have life-long health effects, Swiss researchers have found.

A study published on Monday claims to be the first evidence that IVF has a long-term impact and teens born via assisted reproduction were six times more likely to have clinically high blood pressure as those conceived naturally.

The researchers, from the University Hospital in Bern, say this may be down to the unmeasured impact of the techniques which see sperm and egg stored in an artificial medium and manipulated to form an embryo.

This study was small, with fewer than 100 subjects, but it follows data from animal tests which found blood vessels and heart abnormalities were more common with mice born through IVF, and has sparked calls for much larger safety trials.

“There is growing evidence that artificial reproduction techniques (ART) alters the blood vessels in children, but the long-term consequences were not known,” said Dr Emrush Rexhaj, a blood pressure expert and lead author of the study.

“We now know that this places children [born through artificial reproduction] at a six times higher rate of hypertension (high blood pressure) than children conceived naturally.”

Dr Rexhaj told The Independent: “This is the first demonstration of increased prevalence of a cardiovascular disease [in children conceived through IVF].”

But he said a 2014 study has suggested these patients may also be more at risk of Type 2 diabetes, adding: “There is already evidence showing insulin resistance in this population.”

Larger trials would be needed to conclusively show a health risk, experts say this should be considered urgently as the population born through IVF and other techniques is growing rapidly with the earliest births now in middle age.

There are an estimated six million people alive who were conceived with artificial reproduction techniques worldwide and in July, Louise Brown, the first child born through the IVF, celebrated her 40th birthday.

For the study, published in the Journal of the American College of Cardiology on Monday, Dr Rexhaj recruited 97 healthy young people with an average age of 16 – 54 of the subjects were born through IVF.

Under the skin – best of the British Heart Foundation 2018 image prize

Show all 10

1/10Under the skin – best of the British Heart Foundation 2018 image prize

Under the skin – best of the British Heart Foundation 2018 image prize

Subarachnoid vessels

The runner-up image came from Matt MacGregor Sharp, a PhD student at the University of Southampton. The super-high resolution image shows a normal artery at the surface of a rat’s brain and was taken with a powerful scanning electron microscope. These ‘subarachnoid vessels’ supply blood to the brain and also act like a drain to remove toxic waste products. Matt Macgregor’s team are trying to show that failure to remove waste by these vessels is one of the underlying causes of vascular dementia. The researchers took the image using a technique called ‘freeze fracture’, where tissue or cell samples are frozen and then split apart to reveal the hidden layers within the sample so they can be studied in extreme detail. Sitting above the brown brain tissue, the artery appears blue, and its surrounding layer, the pia mater, is shown in purple.

Matt MacGregor Sharp, University of Southampton, British Heart Foundation - Reflections of Research

Under the skin – best of the British Heart Foundation 2018 image prize

Explosive beginnings

Winner: Endothelial cells line all blood vessels in the body, forming a barrier between the circulating blood and the vessel wall. They also help to protect blood vessels from damage and release important chemical messengers which help to control blood pressure. The winning researcher, Courtney Williams, is a Masters student and PhD candidate at Leeds University. Her lab are developing new ways to map the growth of new blood vessels within their surrounding landscape in 3D. Understanding the complex secrets of blood vessel formation could be harnessed to boost the regrowth of damaged blood vessels after a heart attack, and halt blood vessel growth when it’s counterproductive.

Courtney Williams, Leeds University, British Heart Foundation - Reflections of Research

Under the skin – best of the British Heart Foundation 2018 image prize

A snapshot of platelet production - Reflections of Research Supporters’ Favourite

This image from Abdullah Obaid Khan, a PhD student at the University of Birmingham, won the supporters’ favourite. What look like precious jewels are actually platelets forming within the bone marrow. Platelets are the smallest of our circulating blood cells with a hugely important role in preventing bleeding. However, they also play a role in the formation of clots, which can lead to heart attacks and strokes. Abdullah Obaid Khan and his team are studying rare bleeding disorders.

Abdullah Obaid Khan, University of Birmingham, British Heart Foundation - Reflections of Research

Under the skin – best of the British Heart Foundation 2018 image prize

Cardiac collagen web - Shortlist

This colourful image shows the web-like, network of the smallest blood vessels in the heart – the microvessels. Magenta marks the outer collagen layer of the vessels; while orange marks their inner lining and blue the cell nuclei. Dr Neil Dufton, Imperial College London

Dr Neil Dufton, Imperial College London, British Heart Foundation - Reflections of Research

Under the skin – best of the British Heart Foundation 2018 image prize

Heart to Heart - Shortlist

This piece shows four ventricles (from a mouse) arranged into the shape of the hearts four normal chambers. The researchers have used fluorescent markers to recognise certain proteins and created the image using of hundreds of images assembled together. Dr Elisa Avolio and Dr Zexu Dang, University of Bristol

Dr Elisa Avolio and Dr Zexu Dang, University of Bristol, British Heart Foundation - Reflections of Research

Under the skin – best of the British Heart Foundation 2018 image prize

Loving artery - Shortlist

This image shows a cross section of an artery and the different layers which make up the artery wall. Affiliate Professor Silvia Lacchini, University of Glasgow

Silvia Lacchini, University of Glasgow, British Heart Foundation - Reflections of Research

Under the skin – best of the British Heart Foundation 2018 image prize

Oxidative inkblot - Shortlist

This colour explosion shows one of the culprits in cardiovascular disease – an enzyme called NADPH oxidase. The enzyme is considered ‘Janus faced’ because it is important in health, as well as disease. This picture shows the active enzyme in patients who have high blood pressure. Dr Livia de Lucca Camargo, University of Glasgow

Dr Livia de Lucca Camargo, University of Glasgow, British Heart Foundation - Reflections of Research

Under the skin – best of the British Heart Foundation 2018 image prize

Neon skeleton - Shortlist

This image shows the developing blood vessel system of a two day old zebrafish embryo. The researchers used gene enhancers (the on-off switches of genes) to switch on fluorescent markers in different types of endothelial cells – the important cells which line all blood vessels. All blood vessels switch on the red marker, while the veins also switch on the green marker, resulting in yellow veins and red arteries. Dr Svanhild Nornes, University of Oxford

Dr Svanhild Nornes, University of Oxford, British Heart Foundation - Reflections of Research

Under the skin – best of the British Heart Foundation 2018 image prize

Calcium reef - Shortlist

This image shows calcium in blood vessel cells from people who have high blood pressure and resembles Australia’s Great Barrier Reef. Dr Rheure Alves-Lopes, University of Glasgow

Dr Rheure Alves-Lopes, University of Glasgow, British Heart Foundation - Reflections of Research

Under the skin – best of the British Heart Foundation 2018 image prize

Budding blood vessels - Shortlist

This image shows the growing blood vessels in the mouse retina. In red you can see all the blood vessels and in yellow/green you can see the blood vessels that are actively growing (a process called sprouting). PhD candidate Kira Chouliaras, University of Oxford

Kira Chouliaras, University of Oxford, British Heart Foundation - Reflections of Research

The team monitored their blood pressure over 24 hours and looked at other health measures including the stiffness of their blood vessels and traits like body-mass index and smoking.

Children born through ART had higher blood pressure overall and eight of the children in this group were above thresholds for clinical hypertension, compared to one of the 43 control participants.

Looking at their health records five years before the study, they found no discernible differences between the groups.

Experts said factors which led to parent’s infertility – such as being older or pre-existing health conditions – and lifestyle traits could also be responsible for some of these differences.

Professor Robert Norman, a reproductive medicine expert at the University of Adelaide said: “It warrants a much larger study of the hundreds of thousands of IVF-conceived children in Australia who up until now have shown few medical consequences as a result of their conception.”

He added: “It may be that the first few days of exposure of an embryo to artificial culture media may affect a number of developing organs, including the heart and blood vessels.”

Professor Alastair Sutcliffe, professor of general paediatrics at University College London is leading a major study on the long-term impacts of IVF using data from 77,000 patients in England and Wales, and said all the studies too data have been too small to separate risks from the impact of lifestyle factors.

He added. “IVF conceived individuals are generally healthy but at higher risk of Beckwith Weidmann Syndrome diagnosed at birth and also at higher risk of diseases associated with prematurity if born premature.

“Otherwise their health to date – for example with cancer risk – is no different than the population as a whole.”

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