P-772 Cardiovascular autonomic nervous function in singletons conceived after ART with frozen and fresh embryo transfer compared to naturally conceived children
Authors: Mizrak I , Lund M.A.V , Landgrebe A.V , Asserhøj L.L , Greisen G , Clausen T.D , Main K.M , Vejlstrup N.G , Jensen R.B , Pinborg A , Madsen P.L 
Published: June 2022

Abstract

Study question
Do children conceived after assisted reproductive technologies (ART) with frozen or fresh embryo transfer have altered cardiovascular autonomic nervous function compared to naturally conceived children?

Summary answer
Cardiovascular autonomic nervous function was comparable in singletons conceived after ART with frozen or fresh embryo transfer, and naturally conceived children.

What is known already
Cardiovascular autonomic nervous function (CANF) exert important homeostatic mechanisms to prevent major arterial blood pressure fluctuations by adjusting heart rate, cardiac contractility, and peripheral vascular tone. CANF is impaired in children with obesity and diabetes mellitus, and conductance artery stiffness is documented to influence CANF. Previous studies have reported that children conceived after ART are at risk of increased carotid intima-media thickness; insulin resistance; arterial stiffness; and hypertension. This is the first study to investigate CANF in children conceived after ART.

Study design, size, duration
CANF was studied in 110 singletons aged 7-12 years conceived after frozen embryo transfer (FET, N = 35), fresh embryo transfer (fresh-ET, N = 39) or natural conception (NC, N = 36). Children were born between 2009 and 2013. This study was conducted between June 2019 and October 2021.

Participants/materials, setting, methods
Participants were identified through the Danish IVF and Medical Birth Registries. CANF was evaluated by heart rate (HR) changes (ratio to rest) during deep breathing; Valsalva; and active stand test with continuous non-invasive hemodynamic measurements. Anthropometric measures, fasting blood samples, and maternal questionnaires were collected. Neonatal and maternal pregnancy data were collected from the Medical Birth Registry. Children with a history of congenital heart disease or mothers with gestational diabetes or diabetes mellitus were excluded.

Main results and the role of chance
A total of 110 singletons with a median age of 9.0 years were included in this study. We found no significant associations between conception method and our measures of CANF. For FET, fresh-ET, and NC, respectively, the HR-ratio for deep breathing was 1.62 (0.2 SD), 1.62 (0.16) and 1.63 (0.17) (ANOVA-P = 0.97). For Valsalva, the HR-ratio was 1.97 (0.4), 1.88 (0.41) and 1.63 (0.17), respectively (ANOVA-P = 0.24). For the active stand test, the HR-ratio was 1.43 (0.17), 1.41 (0.2) and 1.43 (0.19), respectively (ANOVA-P = 0.91). Associations remained non-significant after adjustment for age, sex, body surface area, body mass index, and mean arterial pressure. In the multivariate analysis, several other factors were significantly associated with HR-ratio for deep breathing: age (β = -0.06, P = 0.03), body surface area (β = 0.79, P = 0.01), body mass index (β = -0.03, P = 0.04), and mean arterial pressure (β =-0.01, P = 0.03), but not with other measures of CANF. All data for CANF were within reference limits. Also, mothers in the ART groups were older at childbirth than NC group as expected. No significant differences were observed in clinical characteristics, including neonatal and other maternal data.

Limitations, reasons for caution
This study is limited by its observational design to draw any firm conclusion on causality. Also, it is a limitation that the pubertal status was not systematically assessed as pubertal hormones may play a role in CANF.

Wider implications of the findings
This study contributes to the current knowledge about cardiovascular health risks in ART children. Reassuringly, this study found that children conceived after ART (frozen or fresh-ET) did not exhibit impaired cardiovascular autonomic nervous function compared to naturally conceived children.

Trial registration number
NCT03719703