High Maternal Serum Estradiol Environment in the First Trimester Is Associated With the Increased Risk of Small-for-Gestational-Age Birth

Context: There are increasing concerns that a disrupted endocrine environment may disturb the growth of the fetus. Assisted reproductive technology (ART) situates gamete/embryo in a supra-physiological estradiol (E-2) environment and, thus, provides an ideal model to investigate this problem. Objective: Our objective was to investigate whether the maternal high-E-2 environment in the first trimester increases the risks of low birth weight (LBW) and small-for-gestational-age (SGA) birth. Methods: In total, 8869 singletons born after fresh embryo transfer (ET) (n = 2610), frozen ET (n = 1039), and natural conception (NC) (n = 5220) and their mothers were included. Birth weight, LBW, SGA, and maternal serum E-2 levels were investigated. Results: The mean serum E-2 levels of women undergoing fresh ET at 4 and 8 weeks of gestation were significantly higher than those of the women undergoing frozen ET and the women with NC (P < .01). Serum E-2 levels of women undergoing fresh ET at 4 and 8 weeks of gestation were positively correlated to those on the day of human chorionic gonadotropin (hCG) administration (r = 0.5 and r = 0.4, respectively; P < 0.01). The birth weight after fresh ET was significantly lower than that after frozen ET and NC (P <. 0.01), with increased incidence of LBW and SGA (P < .05). Furthermore, in the fresh ET group, singletons of mothers with high E-2 levels (>= 10460 pmol/L on the day of hCG administration) had higher risks of LBW (P < .01) and SGA (P < .01) than those with low E-2 levels, and maternal serum E-2 level on the day of hCG administration negatively correlated with the birth weight (P < .01). Conclusions: The maternal high-E-2 environment in the first trimester is correlated with increased risks of LBW and SGA. Evaluation of serum E-2 before ET should be adopted to reduce the possibility of high E-2 exposure to gamete/embryo.