孕期头三个月暴露于高雌二醇环境后子代甲状腺激素谱的改变：一项横断面研究
Altered thyroid hormone profile in offspring after exposure to high estradiol environment during the first trimester of pregnancy: a cross-sectional study.
作者信息
Lv Ping-Ping, Meng Ye, Lv Min, Feng Chun, Liu Ye, Li Jing-Yi, Yu Dan-Qin, Shen Yan, Hu Xiao-Lin, Gao Qian, Dong Shan, Lin Xian-Hua, Xu Gu-Feng, Tian Shen, Zhang Dan, Zhang Fang-Hong, Pan Jie-Xue, Ye Xiao-Qun, Liu Miao-E, Liu Xin-Mei, Sheng Jian-Zhong, Ding Guo-Lian, Huang He-Feng
机构信息
Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China.
International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, 910 Hengshan Road, Shanghai, 200030, China.
出版信息
BMC Med. 2014 Dec 16;12:240. doi: 10.1186/s12916-014-0240-0.
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.
TRIAL REGISTRATION
ChicCTR-OCC-14004682 (22-05-2014).
背景
通过体外受精和胚胎移植（IVF-ET）受孕的婴儿数量不断增加，关注点从妊娠结局转移到了后代的长期健康。母体高雌二醇（E2）是IVF-ET的一个主要特征，并在妊娠的前三个月持续存在。胎儿甲状腺在此期间发育，因此可能会受到超生理水平E2暴露的影响。本研究的目的是调查妊娠早期母体高E2环境是否会增加IVF-ET后出生儿童甲状腺功能障碍的风险。
方法
采用横断面调查设计，对连续到医院就诊的儿童进行面对面访谈。纳入了949名单胎儿童，他们分别是新鲜胚胎移植（ET）后出生的（n = 357）、冷冻胚胎移植后出生的（n = 212）以及自然受孕（NC）的（n = 380），年龄在3至10岁之间。对所有儿童进行了全面检查。同时，还研究了另外183名新生儿，包括55名新鲜胚胎移植儿、48名冷冻胚胎移植儿和80名自然受孕儿。检测了血清T3、FT3、T4、FT4和TSH水平以及妊娠早期不同阶段的母体E2水平。
结果
妊娠早期接受新鲜胚胎移植的女性的平均血清E2水平显著高于接受冷冻胚胎移植或自然受孕的女性。与自然受孕儿童相比，新鲜胚胎移植受孕的3至10岁儿童的甲状腺激素谱，尤其是T4、FT4和TSH水平显著升高。新生儿中也证实了相同的趋势。然而，冷冻胚胎移植组的T4和TSH水平更接近自然受孕组。此外，新鲜胚胎移植儿的T4和FT4水平与妊娠早期母体血清E2水平呈正相关。
结论
妊娠早期母体高E2环境与甲状腺功能障碍风险增加相关。冷冻胚胎移植可降低IVF受孕儿童的甲状腺损伤风险。需要进一步研究来证实这些发现，并更好地确定潜在的分子机制和临床意义。
试验注册
ChicCTR-OCC-14004682（2014年5月22日）。
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