Decreased pulmonary vascular distensibility in adolescents conceived by in vitro fertilization.

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.

Differentiation of photoreceptors in cultured optic vesicles from embryos of Rana esculenta.

Optic vesicles from embryos of Rana esculenta at a stage corresponding to stage 19 in the development of Rana pipiens were cultured for 15 days. The eyes which differentiated in vitro were much smaller than controls of the same age, due partly to the absence of the vitreous body. In many specimens a well-stratified retina surrounded by a layer of pigmented cells was found. The features of all the components of the retinal layers are described. The complete differentiation of photoreceptors, including their outer segments, is the most interesting result obtained in these organ cultures, and is in contrast with the observations previously reported for retinal tissue cultures. The authors suggest that the source of the material (amphibia instead of birds or mammals) is the main reason for this discrepancy. Frog embryo cells are practically self-sufficient since they are endowed with nutritional substances, amongst which Vit. A and antioxidative agents (Vit. E and ascorbic acid) have been indicated as the most important factors for the structural organization and integrity of the outer segments. The role played by the pigment epithelium is also discussed.