Greater CVD risk for children conceived through IVF

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Children conceived through in vitro fertilisation (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. The Independent reports that a study 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 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 in the report. “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.”

Rexhaj is quoted in the report as saying: “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.

The report says there are an estimated 6m 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, Rexhaj recruited 97 healthy young people with an average age of 16-54 of the subjects were born through IVF. 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 in the report that 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 in the report that in all the studies 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.”

Abstract
Background: Assisted reproductive technologies (ART) have been shown to induce premature vascular aging in apparently healthy children. In mice, ART-induced premature vascular aging evolves into arterial hypertension. Given the young age of the human ART group, long-term sequelae of ART-induced alterations of the cardiovascular phenotype are unknown.
Objectives: This study hypothesized that vascular alterations persist in adolescents and young adults conceived by ART and that arterial hypertension possibly represents the first detectable clinically relevant endpoint in this group.
Methods: Five years after the initial assessment, the study investigators reassessed vascular function and performed 24-h ambulatory blood pressure (BP) monitoring (ABPM) in 54 young, apparently healthy participants conceived through ART and 43 age- and sex-matched controls.
Results: Premature vascular aging persisted in ART-conceived subjects, as evidenced by a roughly 25% impairment of flow-mediated dilation of the brachial artery (p < 0.001) and increased pulse-wave velocity and carotid intima-media thickness. Most importantly, ABPM values (systolic BP, 119.8 ± 9.1 mm Hg vs. 115.7 ± 7.0 mm Hg, p = 0.03; diastolic BP, 71.4 ± 6.1 mm Hg vs. 69.1 ± 4.2 mm Hg, p = 0.02 ART vs. control) and BP variability were markedly higher in ART-conceived subjects than in control subjects. Eight of the 52 ART participants, but only 1 of the 43 control participants (p = 0.041 ART vs. controls) fulfilled ABPM criteria of arterial hypertension (>130/80 mm Hg and/or >95th percentile).
Conclusions: ART-induced premature vascular aging persists in apparently healthy adolescents and young adults without any other detectable classical cardiovascular risk factors and progresses to arterial hypertension.

Authors
Théo A Meister, Stefano F Rimoldi, Rodrigo Soria, Robert von Arx, Franz H Messerli, Claudio Sartori, Urs Scherrer, Emrush Rexhaj

The Independent report
Journal of the American College of Cardiology abstract


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