High Estradiol Environment After IVF Causes Increased Risk of Glucose Metabolic Dysfunction in Offspring

Abstract

Context: Assisted reproductive technology (ART) is associated with increased metabolic risks in offspring. The effect of high maternal estradiol (E2) levels during early pregnancy on the glucose metabolism of offspring remains unclear.

Objective: This work aimed to evaluate glucose metabolism in children conceived via in vitro fertilization (IVF) and to assess whether high E2 exposure during early pregnancy is associated with metabolic alterations.

Methods: This retrospective analysis included 500 singletons aged 3 to 10 years born after fresh embryo transfer (ET) (n = 200), frozen ET (n = 100), and natural conception (NC) (n = 200) from a university hospital. Children underwent anthropometric measurements and examinations for fasting glucose, insulin, and lipid levels. A mouse model of high E2 exposure during early pregnancy was established to study glucose and insulin tolerance, and insulin secretion.

Results: Compared with NC, children born after fresh ET showed higher fasting glucose/insulin levels, increased insulin resistance, and higher incidence of impaired fasting glucose, which might be associated with higher maternal E2 levels. Frozen ET showed intermediate results. In mice, offspring exposed to high E2 levels during gestation exhibited impaired glucose/insulin tolerance and defects in insulin secretion.

Conclusion: High maternal E2 levels in early pregnancy are associated with altered glucose metabolism and increased metabolic risks in IVF-conceived children. Further studies are needed to elucidate the underlying mechanisms.

Keywords: IVF; estradiol; glucose metabolism; insulin resistance; islet; offspring.