Lohstroh Pete, Dong Hongxing, Chen Jiangang, Gee Nancy, Xu Xiping, Lasley Bill
Center for Health and the Environment, University of California, Davis, California 95616-8615, USA.
Biol Reprod. 2006 Jul;75(1):24-33. doi: 10.1095/biolreprod.105.048363. Epub 2006 Mar 8.
A need exists for broadly applicable biomarkers of pregnancy outcome in population-based studies that assess environmental hazards to human reproduction. Previous studies have demonstrated that during the periimplantation period, measures of the circulating levels of immunoreactive hCG (IhCG) are not predictive of pregnancy outcome, whereas measurements of the circulating levels of bioactive hCG (BhCG) provide information relating to pregnancy outcome and might provide the basis for an early biomarker of pregnancy outcome. However, for this biomarker to have broad application in population-based studies, it must be adapted to urinary hCG metabolites. The principle objective of the present study was to characterize the periimplantation excretion patterns of urinary hCG metabolites of pregnancies that resulted in live birth (LB), early pregnancy loss (EPL), and recognized clinical abortion (CAB) with an immunoenzymometric assay specific to intact hCG and an LH/chorionic gonadotropin cellular bioassay as the basis for a preliminary comparison between successful (LB) and failing (EPL and CAB) outcome groups. Automated immunoassays for FSH and hCG were used to define each conceptive cycle's implantation window. The timing of first hCG detection was significantly later for the EPL group. Pregnancies that resulted in LB had consistently rising average daily IhCG and BhCG levels, with no significant differences when average daily IhCG and BhCG measurements were compared (Student t-test, P>0.05), whereas pregnancies that resulted in CAB and EFL had lower average daily IhCG and BhCG levels that increased inconsistently. These findings demonstrate that critical information related to pregnancy outcome may be present when multiple urinary hCG isoforms are measured. Further data suggest that the rate of change for the ratio of daily BhCG over IhCG levels might be useful as the basis of a broadly applicable early biomarker for pregnancy outcome.
在评估人类生殖环境危害的人群研究中，需要广泛适用的妊娠结局生物标志物。先前的研究表明，在植入前期，免疫反应性hCG（IhCG）循环水平的测量不能预测妊娠结局，而生物活性hCG（BhCG）循环水平的测量可提供与妊娠结局相关的信息，并可能为妊娠结局的早期生物标志物提供依据。然而，要使这种生物标志物在人群研究中得到广泛应用，就必须适用于尿hCG代谢物。本研究的主要目的是，采用针对完整hCG的免疫酶测定法和LH/绒毛膜促性腺激素细胞生物测定法，对活产（LB）、早期妊娠丢失（EPL）和确诊临床流产（CAB）的妊娠尿hCG代谢物植入前期排泄模式进行特征分析，作为成功（LB）和失败（EPL和CAB）结局组之间初步比较的基础。使用FSH和hCG的自动化免疫测定法来确定每个受孕周期的植入窗口。EPL组首次检测到hCG的时间明显更晚。导致LB的妊娠平均每日IhCG和BhCG水平持续上升，比较平均每日IhCG和BhCG测量值时无显著差异（Student t检验，P>0.05），而导致CAB和EFL的妊娠平均每日IhCG和BhCG水平较低且上升不一致。这些发现表明，测量多种尿hCG异构体时可能存在与妊娠结局相关的关键信息。进一步的数据表明，每日BhCG与IhCG水平之比的变化率可能作为广泛适用的妊娠结局早期生物标志物的基础。
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