O-201 Growth of singletons born after frozen embryo transfer until early adulthood: a Finnish register study
Authors: Terho A , Tiitinen A , Salo J , Martikainen H , Gissler M , Pelkonen S 
Published: June 2023

Study question

Does the growth of children born after frozen embryo transfer (FET) differ from those born after fresh embryo transfer (ET) or natural conception (NC)?

Summary answer

Boys born after FET have a higher risk of overweight compared to fresh ET.

What is known already

FET is associated with a higher mean birth weight and an increased risk of large-for-gestational-age (LGA) compared to fresh ET and NC, thus raising questions of possible growth disturbances later in life. Previous studies on early childhood growth after FET have reported partly contradictory results. Moreover, data on the adolescent growth after FET are scarce, reporting no significant differences.

Study design, size, duration

This observational cohort study, based on national population-based registers, includes 1825 and 2933 singletons born after FET and fresh ET in Oulu and Helsinki city areas in Finland between 1995 and 2006. A 10% sample of NC controls (n = 31 136) from the same birth years, matched for area of residence, was obtained from the Finnish Medical Birth Register. Growth data were obtained from the Register of Primary Health Care visits.

Participants/materials, setting, methods

Mean heights, weights, and body mass indices (BMI) were compared between the groups, stratified by sex, between ages 7 and 18, using general linear model. The proportions of overweight (age- and sex-adjusted ISO-BMI for children ≥ 25) were analyzed using multiple linear regression, adjusting for birth year, preterm birth, maternal age, parity, and socioeconomic status. Additionally, the odds for overweight were calculated for all ages combined, adjusting for multiple measurements using generalized estimating equations.

Main results and the role of chance

Growth measurements for each age were available for 5.9-30.6% of boys and 4.7-29.5% of girls. The mean and median number of measurements was three per child. No significant differences in height were found between FET and fresh ET. FET boys were significantly taller compared to NC between ages 11 and 14. For boys, the mean proportions of overweight for FET, fresh ET and NC were 28%, 22% and 26%, respectively (p &lt; 0.001 for FET vs fresh ET, p = 0.014 for FET vs NC and p &lt; 0.001 for fresh ET vs NC). For all ages combined, the adjusted odds ratio (aOR) of overweight was 1.14 (95% CI 1.02-1.27) for FET compared to fresh ET, and 1.08 (95% CI 0.99-1.18) for FET compared to NC. For girls, the mean proportions of overweight for FET, fresh ET and NC were 18%, 19% and 22% (p = 0.169 for FET vs fresh ET, p &lt; 0.001 for FET vs NC and p &lt; 0.001 for fresh ET vs NC). For all ages combined, the aOR of overweight was 0.92 (95% CI 0.81-1.06) for FET compared to fresh ET and 0.89 (95% CI 0.80-0.99) for FET compared to NC.

Limitations, reasons for caution

Unfortunately, we were not able to adjust for parental anthropometric characteristics. The growth data were not available for the entire cohort, and the proportion of children measured at the start and end of the follow-up was limited. Mainly cleavage stage embryos were transferred, and slow freezing was used.

Wider implications of the findings

The lack of significant height differences between FET and fresh ET offers reassurance of the safety and feasibility of FET. However, the risk of overweight among FET boys warrant further research as to verify the results in larger cohorts, and further investigate the mechanisms that explain this gender-specific finding.

Trial registration number

not applicable