Vigorous growth through neonatal period to early childhood in offspring born after frozen embryo transfer: a prospective cohort study

Background: Millions of births worldwide were conceived by assisted reproductive technology (ART) and the proportion of frozen embryo transfer (FET) was increasing in recent years. The health of offspring born after FET has been of much concern. But the impact of FET on long-term growth of children was still unknown. The purpose of our study was to compare perinatal outcomes and subsequent growth through childhood between siblings conceived by frozen versus fresh embryo transfer. The results would provide additional evidence to evaluate the long-term safety of FET. Methods: : This cohort study was conducted among participants recruited from 2008 to 2019. Participants were 413 singleton sibling pairs conceived by assisted reproductive technologies (ART) in a single reproductive center. One was born after fresh embryo transfer and the consecutive sibling was born after FET, or vice versa. Pregnant and neonatal complications were obtained through medical records. Children height, weight and head circumference were measured using a stadiometer and scale with calibrated electronic scale. Results: : The prevalence of large for gestational age (LGA) were significantly higher in FET group [adjusted OR = 2.42 (95% confidence interval (CI): 1.39, 4.24)]. We further divided our cohort into two groups, first Fresh/second FET siblings (n=756) and first FET/second Fresh siblings (n=70). The risk of LGA were still higher in frozen embryo transfer children in both groups. The z-score of children length was significantly higher in frozen embryo transfer group (adjusted β 0.96, 95% CI: 0.38,1.54). The z-score of height, BMI as well as HC were comparable between two groups. Conclusion: This study found that the risk of LGA in newborns and z-score of children length are significantly higher in children born from FET than their siblings born from fresh embryo transfers. Long-term follow-up studies should be performed on children born after FET to evaluate their metabolic and growth status. Also, caution should be exercised in freezing all embryos in ART.