title: High maternal serum estradiol environment in the first trimester is associated with the increased risk of small-for-gestational-age birth.
abstract: BACKGROUND
  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 supraphysiological estradiol (E2) environment and, thus, provides an ideal model to investigate this problem.
  
  
  OBJECTIVE
  Our objective was to investigate whether the maternal high-E2 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 E2 levels were investigated.
  
  
  RESULTS
  The mean serum E2 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 E2 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 E2 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 E2 levels, and maternal serum E2 level on the day of hCG administration negatively correlated with the birth weight (P < .01).
  
  
  CONCLUSIONS
  The maternal high-E2 environment in the first trimester is correlated with increased risks of LBW and SGA. Evaluation of serum E2 before ET should be adopted to reduce the possibility of high E2 exposure to gamete/embryo.
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University) (X.-L.H., C.F., X.-H.L., Z.-X.Z., Y.-M.Z., P.-P.L., M.L., Y.M., D.Z., X.-E.L., F.J., J.-Z.S., H.-F.H.), and Department of Reproductive Endocrinology (X.-L.H., C.F., X.-H.L., Z.-X.Z., Y.-M.Z., P.-P.L., M.L., Y.M., D.Z., X.-E.L., F.J., J.X., H.-F.H.), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China; Department of Pathology and Pathophysiology (J.-Z.S.), School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China; and International Peace Maternity and Child Health Hospital (H.-F.H.), Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Hu
authors.forename: Chun
authors.initials: C
authors.lastname: Feng
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Lin
authors.forename: Zi-Xing
authors.initials: ZX
authors.lastname: Zhong
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zhu
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Lv
authors.forename: Min
authors.initials: M
authors.lastname: Lv
authors.forename: Ye
authors.initials: Y
authors.lastname: Meng
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Xiu-E
authors.initials: XE
authors.lastname: Lu
authors.forename: Fan
authors.initials: F
authors.lastname: Jin
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Sheng
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: He-Feng
authors.initials: HF
authors.lastname: Huang
mesh_terms: D001724:Birth Weight; D016022:Case-Control Studies; D006063:Chorionic Gonadotropin / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D004624:Embryo Transfer / Q000009:adverse effects / Q000706:statistics & numerical data; D004958:Estradiol / Q000097:blood*; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects / Q000706:statistics & numerical data; D005317:Fetal Growth Retardation / Q000097:blood* / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000097:blood*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011297:Prenatal Exposure Delayed Effects / Q000097:blood* / Q000453:epidemiology; D011374:Progesterone / Q000097:blood; D012307:Risk Factors
chemical_list: D006063:Chorionic Gonadotropin; D011374:Progesterone; D004958:Estradiol