O-200 Cardiometabolic health in Danish children aged 7-10 years born after assisted reproductive technology with frozen and fresh embryo transfer
Authors: Asserhøj L L , Mizrak I , Lebech Kjaer A S , Clausen T D , Greisen G , Main K M , Lav Madsen P , Pinborg A , Beck Jensen R 
Published: June 2023

Abstract

Study question
Is cardiometabolic health in children conceived after frozen embryo transfer (FET) different from children conceived after fresh embryo transfer (fresh-ET) and natural conception (NC)?

Summary answer
FET-children had similar anthropometrics, glucose- and lipid profile in childhood compared to fresh-ET and NC. Blood pressure was higher in FET-girls compared to fresh-ET-girls.

What is known already
Children conceived after assisted reproductive technology (ART) with FET are more often born large-for-gestational age (LGA) while children born after fresh-ET are at risk of being small-for-gestational age (SGA).In general, children born LGA or SGA are at increased risk of obesity, diabetes and cardiovascular disease later in life. Smaller studies on the whole ART-population have raised concerns about premature vascular aging, increased risk of insulin resistance and higher blood pressure. The long-term cardiometabolic health of children born after ART and especially FET is scarcely explored.

Study design, size, duration
This study was part of the large cohort study “Health in Childhood following Assisted Reproductive Technology” (HiCART) which included 606 singletons (292 boys) born between December 2009 and December 2013: 200 children were conceived after FET; 203 children were conceived after fresh-ET; and 203 children were conceived naturally and matched for birth year and sex. The study period lastet from January 2019 to September 2021.

Participants/materials, setting, methods
The children were 7-10 years of age at examination and underwent a clinical examination with anthropometric measurements, pubertal staging and blood pressure measurement. Furthermore a whole-body dual-energy x-ray absorptiometry-scan (DXA) was performed and a fasting blood sample was drawn. Anthropometric measurements and blood pressure were converted to standard deviation scores (SDS) using a Danish reference. The three study groups were compared pairwise using univariate linear regression model.

Main results and the role of chance
Data is presented as mean (SD). Children conceived after FET had significantly higher birth weight (SDS) (0.20 SDS (1.09)) compared to children conceived after fresh-ET (-0.22 SDS (1.00), mean difference: 0.42 SDS (95% CI: 0.21; 0.62)) and NC-children (-0.16 SDS (1.09), mean difference: 0.35 SDS (95% CI: 0.14; 0.57)).
At 7-10 years height (SDS), weight (SDS) and BMI (SDS) were similar between the groups. Fat percentage (DXA) and waist-to-height ratio were also comparable between the groups.
Markers of glucose metabolism were similar in the groups including fasting glucose, C-peptide, HbA1c and insulin resistance (HOMA-IR). Lipid profiles including, cholesterol, LDL and HDL were also similar.
Blood pressure was comparable between the three groups, but stratified on sex girls conceived after FET had significantly higher systolic blood pressure (SDS) (0.75 SDS (0.84)) compared to girls concieved after fresh-ET (0.49 SDS (0.61), mean difference: 0.25 SDS (95% CI: 0.05; 0.45)) and significantly higher diastolic blood pressure (SDS) (FET: 0.54 SDS (0.57), fresh-ET: 0.38 (0.58), mean difference: 0.16 SDS (0.00; 0.31)). Puberty had started in 17% of the girls, equally distributed in the three groups.

Limitations, reasons for caution
As the participation rate was between 18-42% in the three groups, selection bias cannot be excluded. We currently do not have information regarding endometrial preparation protocol in the FET-cycles which may bias the results. Due to multiple testing type I errors cannot be excluded.

Wider implications of the findings
Higher birth weight in children conceived after FET did not translate into differences in anthropometrics, glucose- or lipid profile in children ages 7-10 years. However, the higher systolic- and diastolic blood pressure (SDS) found in girls concieved after FET compared to fresh-ET is of concern and should be further explored.

Trial registration number
NNF18OC0034092, NFF19OC0054340