Assessing Cardiovascular Remodeling In Fetuses And Infants Conceived By Assisted Reproductive Technologies With Speckle-tracking Imaging

Objective: Assisted reproductive technologies(ART),namely in vitro fertilization(IVF)and intracytoplasmic sperm injection(ICSI),permit childbirth in many infertile couples.Although ART is widely used recently,the potential association of ART with poorer cardiovascular outcomes is not fully investigated.Epidemiological studies have demonstrated an association between pathological events during fetal development and future cardiovascular risk.Several previous studies have found that some early cardiovascular changes have implications for the incidence of cardiovascular disease.Therefore,we can conduct research on populations at increased cardiovascular risk to detect subclinical cardiovascular alterations,and predict outcome.And take early measures to prevent the progression of cardiovascular disease.Valenzuela-Alcaraz et al found a possible association between ART and cardiovascular remodelling in fetal life that persisted in postnatal life.However,previous studies investigated ventricular function by relatively basic techniques,such as mitral/tricuspid ring displacement,left ventricular ejection fraction(LVEF)and tissue doppler imaging(TDI)assessments,etc.Although these techniques are relatively mature,they cannot evaluate the deformation of left ventricle(LV)and right ventricle(RV)myocardium.In recent years,many new ultrasound technologies have emerged,through which we can understand the movement of myocardium,and two-dimensional speckle tracking imaging(STI)is one of them.STI provide not only the cardiac myocardial deformation of each segment of LV and RV,but also the overall cardiac myocardial deformation of LV.The authors hypothesize that fetuses conceived by ART present signs of cardioventricular dysfunction,which can be detected by STI.To address these issues,we will assess comprehensive cardiovascular structure and function in ART offspring(fetal and infant)and explore the role of STI in myocardial deformation.Through this study,we hope to provide new ideas for early detection and prevention of cardiac diseases in offspring conceived by ART.Method:1.Patient recruitment: This study was a prospective cohort study performed with informed consent.This study includedfull-term singleton pregnancies and divided them into ART group and control group.The study was conducted at Shengjing Hospital of China Medical University,Shenyang,China.Between December 2017 and April 2019,100 pregnancies conceived by ART and 100 controls were enrolled.2.Fetal echocardiography at 28-32 weeks of gestation:At inclusion,a baseline assessment of the mothers and ART characteristics were recorded by interview and review of medical records.And a detailed fetal cardiac assessment was performed,including an assessment of fetoplacental Doppler and fetal echocardiography.The fetal echocardiography included the basic measurements of the fetal heart and STI assessment.3.Upon delivery,maternal and neonatal characteristics were assessed.Within 60 days of birth,the first postnatal cardiac assessment was conducted which included the basic measurements of the infants’heart and STI assessment.4.At 6 months of age,the second infants’follow-up evaluation included echocardiography.Echocardiography at the age of six months was the same as that of the two-month age.Data was presented as mean±SD,median(interquartile range)or percentages where appropriate.Independent t test,Wilcoxon rank sum test,Pearson’sχ2 test and linear regression analysis were used,if necessary.A p<0.05 was considered statistically significant.Results:1.During fetal period,ART fetuses showed signs of cardiac remodeling,including morphology and function changes of LV and RV.Compared with the control group,ART fetuses showed decrease in uterine arterial pulsatility index,LV sphericity index of the middle segment,heart-to-thoracic ratio,mitral and tricuspid rings displacement,and increased LV and RV areas,peak E’of the mitral ring and the mitral E/A.Fetuses conceived by ART demonstrated lower LV circumferential strain(circumferential strain of every layers of LV apical myocardium,circumferential strain of epicardial layer of LV middle myocardium,circumferential strain of mid and epicardial layers of LV myocardium,and full-wall of LV circumferential strain).In addition,fetuses conceived by ART demonstrated significantly lower LV longitudinal strain(longitudinal strain in endocardial,midcardial and epicardial layers of LV two-chamber,three-chamber,and four-chamber views,longitudinal strain in endocardial,midcardial and epicardial layers of LV and longitudinal strain of the full-wall LV).Compared with the control group,fetuses conceived by ART demonstrated lower RV longitudinal strain(the longitudinal strain in endocardial and midcardial layers of the RV and the longitudinal strain ofthe full-wall RV).2.ART infants aged less than two months old showed persistent cardiac changes,including LV function and RV morphology.Compared with the control group,ART children showed reduction of the RV sphericity index of the middle segment,and prolonged LV isovolumic relaxation time.Measuring LVEF by STI and biplane Simpson method,it was found that LVEF in ART group was significantly reduced.There were no differences in LV and RV longitudinal strain and LV circumferential strain between the two groups.3.The offsprings of ART aged at six months showed LV and RV morphology and function changes.ART children showedincreases in the areas of the left atrium,LV,and RV,the RV myocardial thickness,and in RV stroke volume and cardiac output.The LVEF was measured by the biplane Simpson method through STI,and the end-diastolic volume of LV was increased.Compared with the control group,children conceived by ART demonstrated significantly lower LV longitudinal strain(longitudinal strain in endocardial,midcardial and epicardial layers of LV two-chamber view,longitudinal strain in epicardial layers of LV three-chamber view,longitudinal strain in endocardial,midcardial and epicardial layers of LV and longitudinal strain of the full-wall LV).Conclusion:Measuring by STI,children conceived by ART manifest ventricular morphology and function changes that is present in fetal life and persists in postnatal life,suggesting cardiac remodeling in ART offsprings.At the same time,STI can provide more ventricular motion information to detect subclinical changes in myocardial function in ART offspring.From a clinical perspective,these findings provide important ideas for early detection of cardiovascular health in relevant populations.