Right ventricular dysfunction in children and adolescents conceived by assisted reproductive technologies

Abstract

Assisted reproductive technologies (ART) predispose the offspring to vascular dysfunction, arterial hypertension, and hypoxic pulmonary hypertension. Recently, cardiac remodeling and dysfunction during fetal and early postnatal life have been reported in offspring of ART, but it is not known whether these cardiac alterations persist later in life and whether confounding factors contribute to this problem. We, therefore, assessed cardiac function and pulmonary artery pressure by echocardiography in 54 healthy children conceived by ART (mean age 11.5 ± 2.4 yr) and 54 age-matched (12.2 ± 2.3 yr) and sex-matched control children. Because ART is often associated with low birth weight and prematurity, two potential confounders associated with cardiac dysfunction, only singletons born with normal birth weight at term were studied. Moreover, because cardiac remodeling in infants conceived by ART was observed in utero, a situation associated with increased right heart load, we also assessed cardiac function during high-altitude exposure, a condition associated with hypoxic pulmonary hypertension-induced right ventricular overload. We found that, while at low altitude cardiac morphometry and function was not different between children conceived by ART and control children, under the stressful conditions of high-altitude-induced pressure overload and hypoxia, larger right ventricular end-diastolic area and diastolic dysfunction (evidenced by lower E-wave tissue Doppler velocity and A-wave tissue Doppler velocity of the lateral tricuspid annulus) were detectable in children and adolescents conceived by ART. In conclusion, right ventricular dysfunction persists in children and adolescents conceived by ART. These cardiac alterations appear to be related to ART per se rather than to low birth weight or prematurity.

Fetal programming and epigenetic mechanisms in arterial hypertension

“…Based on emerging data showing that the early embryo is particularly sensitive to environmental insults, we speculated that ART alters cardiovascular function in the offspring. In line with this speculation, we found that young, apparently healthy ART children display signs of premature vascular ageing of the systemic circulation together with pulmonary vascular dysfunction predisposing to exaggerated hypoxic pulmonary hypertension [17][18][19][20]. Most importantly, recent data indicate that ART-induced vascular dysfunction translates into increased arterial blood pressure.…”

“…These differences in blood pressure between ART and control children are clinically important, as childhood blood pressure tracks into later life [23]. Parenthetically, it is well known that arterial hypertension is often associated with insulin resistance [24], and defective nitric oxide-dependent insulin stimulation of blood flow and substrate delivery to skeletal muscle tissue, which leads to insulin resistance in experimental animal models and humans, may represent an underlying mechanism [20,25,26]. Accordingly, a recent study demonstrated insulin resistance in young adults conceived by ART [27], suggesting that ART-induced vascular dysfunction may facilitate diabetes later in life.…”

Effects of perinatal, late foetal, and early embryonic insults on the cardiovascular phenotype in experimental animal models and humans

“…Gratacos et al showed that ART is associated with in utero cardiac remodelling that persists in 6 month old infants [55]. We subsequently demonstrated that cardiac alterations persist into adolescence, as evidenced by larger right ventricular end-diastolic volume and diastolic dysfunction at high altitude [56].…”

Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse

“…Scherrer and colleagues also found that high altitude conditions induced a 30% increase in systolic pulmonary artery pressure in IVF/ICSI children by comparison with naturally conceived children [40]. In a separate report, the same research group observed increased right ventricle end-diastolic area and diastolic dysfunction in IVF/ICSI children at high altitude, but not at low altitude [42]. In both cases, pulmonary hypertension differences were observed only under hypoxic stress.…”