Decreased pulmonary vascular distensibility in adolescents conceived by in vitro fertilization

Abstract

STUDY QUESTION What is the functional relevance of decreased pulmonary vascular distensibility in adolescents conceived by IVF? SUMMARY ANSWER Children born by IVF have a slight decrease in pulmonary vascular distensibility observed during normoxic exercise that is not associated with altered right ventricular function and aerobic exercise capacity. WHAT IS KNOWN ALREADY General vascular dysfunction and increased hypoxic pulmonary hypertension have been reported in ART children as compared to controls. Pulmonary hypertension or decreased pulmonary vascular distensibility may affect right ventricular function and thereby possibly limit maximal cardiac output and aerobic exercise capacity. STUDY DESIGN, SIZE, DURATION This prospective case-control study enrolled 15 apparently healthy adolescents conceived by IVF/ICSI after fresh embryo transfer paired in a 2 to 1 ratio to 30 naturally conceived adolescents between March 2015 and May 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Fifteen IVF/ICSI adolescents and 30 controls from singleton gestations matched by age, gender, weight, height and physical activity underwent exercise echocardiography, lung diffusion capacity measurements and a cycloergometer cardiopulmonary exercise test. A pulmonary vascular distensibility coefficient α was determined from the pulmonary arterial pressure (PAP) versus cardiac output (Q) relationships. Pulmonary capillary volume (Vc) was calculated from single breath nitric oxide and carbon monoxide lung diffusion capacity measurements (DLCO and DLNO) at rest and during exercise (100 W). Eight of the IVF subjects and eight controls underwent a 30 min hypoxic challenge at rest with a fraction of inspired oxygen of 0.12 to assess hypoxic pulmonary vasoconstriction. MAIN RESULTS AND THE ROLE OF CHANCE In normoxia, oxygen uptake (VO2), blood pressure, DLCO, DLNO, echocardiographic indices of right ventricular function, Q and PAP at rest and during exercise were similar in both groups. However, IVF children had a lower pulmonary vascular distensibility coefficient α (1.2 ± 0.3 versus 1.5 ± 0.3%/mmHg, P = 0.02) and a blunted exercise-induced increase in Vc (24 versus 32%, P < 0.05). Hypoxic-induced increase in pulmonary vascular resistance in eight IVF subjects versus eight controls was similar. LIMITATIONS, REASONS FOR CAUTION The IVF cohort was small, and thus type I or II errors could have occurred in spite of careful matching of each case with two controls. ART evolved over the years, so that it is not certain that the presently reported subtle changes will be reproducible in the future. As the study was limited to singletons born after fresh embryo transfers, our observations cannot be extrapolated to singletons born after frozen embryo transfer. WIDER IMPLICATIONS OF THE FINDINGS The present study suggests that adolescents conceived by IVF have preserved right ventricular function and aerobic exercise capacity despite a slight alteration in pulmonary vascular distensibility as assessed by two entirely different methods, i.e. exercise echocardiography and lung diffusing capacity measurements. However, the long-term prognostic relevance of this slight decrease in pulmonary vascular distensibility needs to be evaluated in prospective large scale and long-term outcome studies. STUDY FUNDING/COMPETING INTEREST(S) Dr Caravita was supported by an ERS PAH short term research training fellowship (STRTF2014-5264). Dr Pezzuto was funded by an Italian Society of cardiology grant. Dr Motoji was supported by a grant from the Cardiac Surgery Funds, Belgium. All authors have no conflicts of interests to declare.

Exercise stress echocardiography of the pulmonary circulation and right ventricular-arterial coupling in healthy adolescents

“…The distensibility factor a has been shown to be higher in pre-menopausal women and lower in aging adults, 19 lower in young adult men of Sub-Saharan African ascendance 20 lower with chronic but not acute hypoxic exposure 2,21 or diesel exhaust exposure, 22 and lower in adolescents born by in vitro fertilization. 14 The a factor has been reported to be decreased in patients with borderline hypertension, 23 early or latent pulmonary vascular disease, 5,24 and heart failure. 6,24 A decreased pulmonary vascular distensibility results in higher PA pressures during exercise, which may be associated with insufficient RV function adaptation, RV-PA uncoupling and decreased aerobic exercise capacity, in healthy subjects 19,25 and more so in heart failure patients.…”

“…On the first visit, the participant underwent a clinical examination and a standard resting echocardiographic examination followed by an incremental stress echocardiography. The exercise echocardiography was performed on a semi-recumbent position as previously reported 14 with an incremental workload increase of 20 W/2 min until exhaustion. The second visit consisted of a standard incremental cardiopulmonary exercise test (CPET) on a cycle ergometer to measure ventilation (V E ), carbon dioxide output (VCO 2 ), and oxygen uptake (VO 2 ).…”

“…The CPET were performed as previously reported 14 with breath by breath measurements of VO 2 , VCO 2 , and VE on a cycle ergometer at progressively increased workload (HypAir; Medisoft; Dinant, Belgium) of 10-30 W/min until volitional fatigue for an optimal test duration between 10 and 12 min for all subjects. SpO 2 and HR were measured continuously.…”

Beta-Adrenergic Receptor Blockade Effects on Cardio-Pulmonary Exercise Testing in Healthy Young Adults: A Randomized, Placebo-Controlled Trial

“…The cycle ergometer CPET were performed in an upright position as previously reported with a warm-up of 3 min set at 60 W for men and 30 W for women and workload increased by 30 W/min for men and 20 W/min for women until volitional fatigue [ 19 ]. The recovery period consisted in pedaling at 60 round per minute at 60 W for men and 30 W for women for 2 min.…”

Beta-adrenergic Receptor Blockade Effects on Cardio-pulmonary Exercise Testing

“…The cycle ergometer CPET were performed as previously reported with a warm-up of 3 minutes set at 60W for men and 30W for women and workload increased by 30 W/min for men and 20 W/min for women until volitional fatigue [17]. The recovery period consisted in pedaling at 60 round per minute at 60 W for men and 30 W for women for 2 minutes.…”