Scherrer, U., Rexhaj, E., Allemann, Y., Sartori, C., & Rimoldi, S. F. (2015). Cardiovascular dysfunction in children conceived by assisted reproductive technologies. European heart journal. https://doi.org/10.1093/eurheartj/ehv145
Scherrer U, Rexhaj E, Allemann Y, Sartori C, Rimoldi SF. Cardiovascular dysfunction in children conceived by assisted reproductive technologies. European heart journal. 2015. doi:10.1093/eurheartj/ehv145
Scherrer, Urs, et al. "Cardiovascular dysfunction in children conceived by assisted reproductive technologies." European heart journal, 2015.
Children conceived by ART show blood vessel dysfunction
A 2015 review by cardiologists of studies in children and mice reports that apparently healthy children conceived by ART show more blood vessel dysfunction than control children. Flow-mediated vasodilation was roughly 25% smaller. A cited study reported higher blood pressure in these children. The authors also describe added pregnancy risks and urge long-term follow-up.
Study at a glance, narrative review of children and mice: Children conceived by ART showed more blood vessel dysfunction. Source: Scherrer U et al., 2015, PMID 25911649.
Key Findings
In the brachial artery, the widening that follows a brief blood flow increase, called flow-mediated vasodilation, is roughly 25% smaller in ART children than in control children.
ART children have significantly faster carotid-femoral pulse wave velocity, which indicates stiffer arteries, and significantly thicker carotid intima-media than controls.
A follow-up study that the review cites found higher clinic blood pressure, both systolic and diastolic, in ART children than in spontaneously conceived controls.
Mice generated by in vitro fertilization and fed a Western style high-fat diet lived roughly 25% shorter lives than control mice.
The vascular dysfunction appeared similar after in vitro fertilization, intra-cytoplasmic sperm injection, frozen zygote transfer and fresh embryo transfer. The dysfunction also appeared in children born at term with normal birth weight.
Interpretation
The paper is a narrative review by cardiologists. It summarizes the authors' own studies in children and mice together with other published work. The children were young and apparently healthy. The authors expect data on stroke and similar endpoints only in 20–30 years. They note that parental factors are hard to exclude fully in humans, although their observations suggest the procedure itself is responsible. Some ambulatory blood pressure data are preliminary. The authors advise using ART parsimoniously.
RRM Context
Restorative reproductive medicine looks for the cause of infertility and treats it. Conception then takes place in the body. Those embryos spend no time in a laboratory culture dish. The authors suggest that suboptimal culture conditions contribute to vascular changes in mice. IVF bypasses infertility and leaves the cause unresolved. The review also cites added pregnancy risks with ART, such as pre-eclampsia and premature birth.
Our editorial summary of this paper, not the article's abstract.
Abstract
Epidemiological studies demonstrate a relationship between pathological events during foetal development and future cardiovascular risk and the term 'foetal programming of cardiovascular disease' has been coined to describe this phenomenon. The use of assisted reproductive technologies (ARTs) is growing exponentially and 2-5% of children are now born by this procedure. Emerging evidence indicates that ART represents a novel important example of foetal programming. Assisted reproductive technology may modify the cardiovascular phenotype in two ways: (i) ART involves manipulation of the early embryo which is exquisitely sensitive to environmental insults. In line with this concern, ART alters vascular and cardiac function in children and studies in mice show that ART alters the cardiovascular phenotype by epigenetic alterations related to suboptimal culture conditions. (ii) Assisted reproductive technology markedly increases the risk of foetal insults that augment cardiovascular risk in naturally conceived individuals and are expected to have similar consequences in the ART population. Given the young age of the ART population, it will take another 20-30 years before data on cardiovascular endpoints will be available. What is clear already, however, is that ART emerges as an important cardiovascular risk factor. This insight requires us to revise notions on ART's long-term safety and to engage on a debate on its future. There is an urgent need to better understand the mechanisms underpinning ART-induced alteration of the cardiovascular phenotype, improve the procedure and its long-term safety, and, while awaiting this aim, not to abandon medicine's fundamental principle of doing no harm (to future children) and use ART parsimoniously.
