Cardiovascular dysfunction in children conceived by assisted reproductive technologies.
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.
Department of Cardiology, University Hospital, Bern CH-3010, Switzerland Department of Clinical Research, University Hospital, Bern CH-3010, Switzerland Facultad de Ciencias, Departamento de Biología, Universidad de Tarapacá, Arica, Chile urs.scherrer2@insel.ch.
Urs
U
Scherrer
Department of Cardiology, University Hospital, Bern CH-3010, Switzerland Department of Clinical Research, University Hospital, Bern CH-3010, Switzerland.
Emrush
E
Rexhaj
Department of Cardiology, University Hospital, Bern CH-3010, Switzerland Department of Clinical Research, University Hospital, Bern CH-3010, Switzerland.
Yves
Y
Allemann
Department of Internal Medicine, University Hospital, Lausanne, Switzerland.
Claudio
C
Sartori
Department of Cardiology, University Hospital, Bern CH-3010, Switzerland Department of Clinical Research, University Hospital, Bern CH-3010, Switzerland.
Stefano F
SF
Rimoldi
D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000517:prevention & control; D002648:Child; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D047109:Fetal Development / Q000502:physiology; D005544:Forecasting; D006801:Humans; D051379:Mice; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects* / Q000639:trends; D012307:Risk Factors; D066253:Vascular Remodeling / Q000502:physiology
D052250:Nitric Oxide Synthase Type III
Arterial hypertension; Endothelium; Epigenetic; In vitro fertilization; Pulmonary hypertension; eNOS