title: Altered thyroid hormone profile in offspring after exposure to high estradiol environment during the first trimester of pregnancy: a cross-sectional study.
abstract: BACKGROUND
  The increasing number of babies conceived by in vitro fertilization and embryo transfer (IVF-ET) shifts concern from pregnancy outcomes to long-time health of offspring. Maternal high estradiol (E2) is a major characteristic of IVF-ET and lasts throughout the first trimester of pregnancy. The fetal thyroid develops during this period and may thus be affected by exposure to the supra-physiological E2. The aim of this study is to investigate whether the high E2 maternal environment in the first trimester increases the risk of thyroid dysfunction in children born following IVF-ET.
  
  
  METHODS
  A cross-sectional survey design was used to carry out face-to-face interviews with consecutive children attending the hospital. A total of 949 singletons born after fresh embryo transfer (ET) (n=357), frozen ET (n=212), and natural conception (NC) (n=380), aged 3 to 10 years old, were included. All children were thoroughly examined. Meanwhile, another 183 newborns, including 55 fresh ET, 48 frozen ET, and 80 NC were studied. Levels of serum T3, FT3, T4, FT4, and TSH and levels of maternal E2 at different stages of the first trimester were examined.
  
  
  RESULTS
  The mean serum E2 levels of women undergoing fresh ET during the first trimester of pregnancy were significantly higher than those of the women undergoing frozen ET or following NC. The thyroid hormone profile, especially the levels of T4, FT4, and TSH, were significantly increased in 3- to 10-year-old children conceived by fresh ET compared to NC. The same tendency was confirmed in newborns. However, levels of T4 and TSH in the frozen ET group were nearer to that of the NC group. Furthermore, levels of T4 and FT4 in fresh ET were positively correlated with maternal serum levels of E2 during early pregnancy.
  
  
  CONCLUSIONS
  The maternal high E2 environment in the first trimester is correlated with increased risk of thyroid dysfunction. Frozen ET could reduce risks of thyroid damage in children conceived by IVF. Further studies are needed to confirm these findings and to better determine the underlying molecular mechanisms and clinical significance.
  
  
  BACKGROUND
  ChicCTR-OCC-14004682 (22-05-2014).
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. lvpingping@zju.edu.cn.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. dreamleaves1987@126.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. lvmin3166@zju.edu.cn.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. doctorfc@126.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. liuye90s@126.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. ydq1002@zju.edu.cn.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. sy825@zju.edu.cn.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. xiaolinghu1982@163.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. gaoqian198636@163.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. dongshan@zju.edu.cn.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. xl_1290@126.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. 54paladin@gmail.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. luofeibaba31@hotmail.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. zhangdan61@hotmail.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. timechance@vip.sina.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. nuonuoever@gmail.com.
authors.forename: Jie-Xue
authors.initials: JX
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. 188677077@163.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. 627143479@qq.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. nanlilac@hotmail.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. shengjz@zju.edu.cn.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. dingguolian@hotmail.com.|International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, 910 Hengshan Road, Shanghai, 200030, China. dingguolian@hotmail.com.
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authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. huanghefg@hotmail.com.|International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, 910 Hengshan Road, Shanghai, 200030, China. huanghefg@hotmail.com.
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mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004624:Embryo Transfer; D004958:Estradiol / Q000009:adverse effects*; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000097:blood* / Q000209:etiology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D013963:Thyroid Hormones / Q000097:blood*
chemical_list: D013963:Thyroid Hormones; D004958:Estradiol