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Childhood BMI after ART with frozen embryo transfer
Louise Laub Asserhøj1,2,3, Ikram Mizrak1,4, Gerda Ferja Heldarskard1
1The Fertility Clinic, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Insights
Childhood BMI does not differ between children conceived via frozen embryo transfer (FET) and fresh embryo transfer (fresh-ET) or natural conception (NC). However, girls born after FET showed increased height and weight compared to girls born after NC.
Area of Science:
- Reproductive Medicine
- Pediatric Endocrinology
- Public Health
Background:
- High childhood BMI is linked to adult obesity and cardiometabolic diseases.
- Children conceived via frozen embryo transfer (FET) have a higher risk of being born large for gestational age (LGA).
- Assisted reproductive technology (ART) may induce epigenetic variations influencing fetal size and later health.
Purpose of the Study:
- To compare childhood BMI at 7-10 years in children conceived via FET, fresh-ET, and natural conception (NC).
- To investigate potential differences in body composition based on conception method.
Main Methods:
- A retrospective cohort study (HiCART) of 606 singletons aged 7-10 years.
- Participants were divided into FET, fresh-ET, and NC groups.
- Clinical examinations included anthropometry and dual-energy x-ray absorptiometry; data were analyzed using SDS and regression models.
Main Results:
- Children conceived via FET had significantly higher birthweight (SDS) than fresh-ET and NC groups.
- No significant differences in childhood BMI (SDS) were found between FET, fresh-ET, and NC groups.
- Girls born after FET showed increased height and weight (SDS) compared to NC girls; boys showed no significant differences.
Conclusions:
- Increased birthweight in FET-conceived children did not translate to higher childhood BMI.
- Observed differences in girls suggest potential sex-specific effects of FET on growth.
- Longitudinal studies are needed to assess the long-term cardiometabolic implications for children conceived via FET.
Study Question:
Does BMI at 7-10 years of age differ in children conceived after frozen embryo transfer (FET) compared to children conceived after fresh embryo transfer (fresh-ET) or natural conception (NC)?
Summary Answer:
BMI in childhood does not differ between children conceived after FET compared to children conceived after fresh-ET or NC.
What Is Known Already:
High childhood BMI is strongly associated with obesity and cardiometabolic disease and mortality in adulthood. Children conceived after FET have a higher risk of being born large for gestational age (LGA) than children conceived after NC. It is well-documented that being born LGA is associated with an increased risk of obesity in childhood, and it has been hypothesized that ART induces epigenetic variations around fertilization, implantation, and early embryonic stages, which influence fetal size at birth as well as BMI and health later in life.
Study Design, Size, Duration:
The study 'Health in Childhood following Assisted Reproductive Technology' (HiCART) is a large retrospective cohort study with 606 singletons aged 7-10 years divided into three groups according to mode of conception: FET (n = 200), fresh-ET (n = 203), and NC (n = 203). All children were born in Eastern Denmark from 2009 to 2013 and the study was conducted from January 2019 to September 2021.
Participants/Materials, Setting, Methods:
We anticipated that the participation rate would differ between the three study groups owing to variation in the motivation to engage. To reach the goal of 200 children in each group, we invited 478 in the FET-group, 661 in the fresh-ET-group, and 1175 in the NC-group. The children underwent clinical examinations including anthropometric measurements, whole-body dual-energy x-ray absorptiometry-scan, and pubertal staging. Standard deviation scores (SDS) were calculated for all anthropometric measurements using Danish reference values. Parents completed a questionnaire regarding the pregnancy and the current health of the child and themselves. Maternal, obstetric, and neonatal data were obtained from the Danish IVF Registry and Danish Medical Birth Registry.
Main Results And The Role Of Chance:
As expected, children conceived after FET had a significantly higher birthweight (SDS) compared to both children born after fresh-ET (mean difference 0.42, 95% CI (0.21; 0.62)) and NC (mean difference 0.35, 95% CI (0.14; 0.57)). At follow-up (7-10 years), no differences were found in BMI (SDS) comparing FET to fresh-ET, FET to NC, and fresh-ET to NC. Similar results were also found regarding the secondary outcomes weight (SDS), height (SDS), sitting height, waist circumference, hip circumference, fat, and fat percentage. In the multivariate linear regression analyses, the effect of mode of conception remained non-significant after adjusting for multiple confounders. When stratified on sex, weight (SDS), and height (SDS) were significantly higher for girls born after FET compared to girls born after NC. Further, FET-girls also had significantly higher waist, hip, and fat measurements compared to girls born after fresh-ET. However, for the boys the differences remained insignificant after confounder adjustment.
Limitations, Reasons For Caution:
The sample size was decided in order to detect a difference of 0.3 SDS in childhood BMI (which corresponds to an adult cardiovascular mortality hazard ratio of 1.034). Thus, smaller differences in BMI SDS may be overlooked. As the overall participation rate was 26% (FET: 41%, fresh-ET: 31%, NC: 18%), selection bias cannot be excluded. Regarding the three study groups, many possible confounders have been included but there might be a small risk of selection bias as information regarding cause of infertility is not available in this study.
Wider Implications Of The Findings:
The increased birthweight in children conceived after FET did not translate into differences in BMI, however, for the girls born after FET, we observed increased height (SDS) and weight (SDS) compared to the girls born after NC, while for the boys the results remained insignificant after confounder adjustment. Since body composition in childhood is a strong biomarker of cardiometabolic disease later in life, longitudinal studies of girls and boys born after FET are needed.
Study Funding/Competing Interest(S):
The study was funded by the Novo Nordisk Foundation (grant number: NNF18OC0034092, NFF19OC0054340) and Rigshospitalets Research Foundation. There were no competing interests.
Trial Registration Number:
ClinicalTrials.gov identifier: NCT03719703.
