Zhou, Wei, Feng, Wanbing, Chang, Jinli, Hu, Jingmei, Li, Fuxia, Hu, Kuona, Jiao, Jiejing, Xue, Xinyi, Lan, Ting, Wan, Wenjing, Chen, Zi-Jiang, and Cui, Linlin
Background: Frozen embryo transfer (FET) has become a widely employed assisted reproductive technology technique. There have historically been concerns regarding the long-term metabolic safety of FET technology in offspring due to pregnancy-induced hypertension and large for gestational age, both of which are well-recognized factors for metabolic dysfunction of children. Therefore, we aimed to compare the metabolic profiles of children born after frozen versus fresh embryo transfer at 2 to 5 years of age. Methods and findings: This was a prospective cohort study. Using data from the "Assisted Reproductive Technology borned KIDs (ARTKID)," a birth cohort of offspring born from assisted reproductive technology at the Institute of Women, Children and Reproductive Health, Shandong University, China. We included 4,246 singletons born after FET (n = 2,181) and fresh embryo transfer (n = 2,065) enrolled between 2008 and 2019 and assessed the glucose and lipid variables until the age of 2 to 5 years. During a mean follow-up of 3.6 years, no significant differences were observed in fasting blood glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance Index, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol levels between offspring conceived by fresh and frozen embryo transfer in the crude model and adjusted model (adjusted for parental age, parental body mass index, parental education level, paternal smoking, parity, offspring age and sex). These results remained consistent across subgroup analyses considering offspring age, the stage of embryo transfer, and the mode of fertilization. Results from sensitivity analysis on children matched for age within the cohort remains the same. The main limitation of our study is the young age of the offspring. Conclusions: In this study, the impact of FET on glucose and lipid profiles during early childhood was comparable to fresh embryo transfer. Long-term studies are needed to evaluate the metabolic health of offspring born after FET. Wei Zhou and co-workers explore the impact of fresh Versus frozen embryo transfer on the metabolic profiles of children in China. Author summary: Why was this study done?: Frozen embryo transfer (FET) is a commonly used assisted reproductive technology technique. Concerns have existed about the long-term metabolism of FET for offspring due to increased risk of well-recognized factors for metabolic dysfunction, including pregnancy-induced hypertension, macrosomia, large for gestational age, and elevated birth weight. Limited studies have reported on the metabolic profiles of children born after FET, leaving the potential long-term metabolic safety of FET unclear. What did the researchers do and find?: Using data from the "Assisted Reproductive Technology borned KIDs (ARTKID)," a prospective birth cohort at a Chinese single reproductive center, 4,246 singletons of "ARTKID" cohort at 2 to 5 years of age born after either FET (n = 2,181) or fresh embryo transfer (n = 2,065) were included. The average duration of follow-up across the study was 3.6 years. Assessments included fasting blood glucose, insulin, total cholesterol, triglycerides, low- and high-density lipoprotein cholesterol. The study found no significant differences in various metabolic parameters between children born after frozen versus fresh embryo transfer, even after adjusting for potential confounders, including parental age, body mass index, and other factors [adjusted mean difference (95% CI): fasting blood glucose, −0.01(−0.03, 0.02); total cholesterol, 0(−0.05, 0.04)]. What do these findings mean?: FET does not have a significant adverse impact on glucose and lipid profiles during early childhood. These data provide valuable evidence on the safety of FET when counselling couples undergoing assisted reproductive technology treatment. The main limitations are the young age of the offspring, as they may not fully manifest comprehensive metabolic phenotypic changes at this stage, necessitating longer follow-up studies for a more thorough understanding. [ABSTRACT FROM AUTHOR]