Study of Metals and Assisted Reproductive Technologies(SMART)

金属与辅助生殖技术研究（SMART）

• 批准号: 8964471
• 负责人: Michael S Bloom
• 金额: $ 30.34万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT ALBANY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8964471
• 关键词: Accounting; Age; Analysis of Variance; Arsenic; Asians; Assisted Reproductive Technology; Attention; Biological Markers; Body mass index; Cadmium; Chinese Herbs; Clinic; Clinical; Clinical Protocols; Collection; Complementary therapies; Consumption; Couples; Data; Data Reporting; Diagnosis; Diet; Elements; Embryo; Embryo Transfer; Ensure; Ethics; Ethnic Origin; Evaluation; Exposure to; Failure; Female; Fertility; Fertilization failure; Fertilization in Vitro; Fishes; Follicular Fluid; Goals; Growth; Health behavior; Home environment; Human; In Vitro; Individual; Infertility; Investigation; Lead; Life; Link; Live Birth; Measures; Mercury; Metals; Minority Groups; Modeling; National Health and Nutrition Examination Survey; Oocytes; Outcome; Outcome Study; Ovarian; Ovarian Follicle; Ovary; Oxidative Stress; Participant; Patients; Physicians; Population Study; Predictive Factor; Pregnancy; Procedures; Protocols documentation; Publishing; Race; Recruitment Activity; Reporting; Reproductive Health; Research; Research Design; Research Personnel; Retrieval; Risk Factors; Sampling; Seminal Plasma; Seminal fluid; Solutions; Source; Specimen; Strategic Planning; Time; Toxic Environmental Substances; Toxicant exposure; Trace Elements; Trace metal; Treatment Protocols; United States National Institutes of Health; Visit; Woman; Women' s Health; Work; antioxidant enzyme; base; cigarette smoking; design; enzyme activity; experience; follow-up; health disparity; high risk; innovation; male; modifiable risk; outcome forecast; reproductive; sample collection; sex; success; therapy design; toxicant; traditional therapy

Aims: The overall goal is to characterize the variability of toxic trace elements and anti-oxidant enzyme activities in ovarian follicular fluid (FF) and to identify predictors of variability. A secondary goal is to pilot home seminal plasma (SP) collection and to assess temporal changes in toxic trace elements. Significance: The results of the proposed project will allow us to modify the protocol and analytic strategy for our planned larger study intended to more definitively investigate the impact of trace exposures to toxic elements on in vitro fertilization (IVF) outcomes and race disparities. According to recently released NHANES data, Asians had higher average levels of toxic trace elements than other U.S. race/ethnicities in 2011-2012, including As, Cd, Pb and Hg. In addition, Asian women consistently demonstrate poorer IVF outcomes than white women in the U.S. One probable explanation that has received increasing attention is differential exposure to environmental reproductive toxicants associated with diet and health behaviors, including toxic trace elements. Identification of potentially modifiable toxicant exposures is necessary to design interventions that maximize the likelihood for live birth by IVF or to identify couples with a high risk of failure. However, physicians conducting IVF often collect multiple oocytes, leading to multiple embryos, which are transferred based on clinical factors to maximize the likelihood for a live birth. Investigators are thus unable to ensure oocytes from sampled follicles are transferred and lead to pregnancy and live birth, and so cannot directly link concentrations of analytes measured in FF. Preliminary data from our group and others indicate between-follicles variability for toxic trace elements in FF, and so an inability to implement a one follicle-one pregnancy/delivery investigational study design may reduce statistical power. In the absence of a prohibitively large number of study participants a methodologic solution is required. Innovation: The proposed project is innovative because it is the only study to characterize the variability of toxic trace metals in FF, and to assess their utility as biomarkers of exposure for studying IVF outcomes. Approach: Nearly 1/3 of our U.S. based study population is comprised of Asian women and so we will assess the disparity in relation to toxic trace elements in the normal clinical context of IVF procedures. We will recruit 50 IVF couples from our center, and collect FF from four individual ovarian follicles during oocyte retrieval. We will: 1) measure levels of As, Cd, Pb, Hg and six anti-oxidant enzyme activities in FF to characterize sources of variability between follicles, between ovaries, between women and from analytic factors; 2) consider FF volume, IVF treatment protocol, infertility diagnosis, age, race, body mass index, cigarette smoking, fish consumption and other factors as predictors of FF variability; and 3) pilot a home semen specimen collection strategy to allow evaluation of longitudinal changes in SP toxic trace elements. The likelihood of success is enhanced by the extensive collaborative experience and expertise of the research team.

目的：总体目标是表征卵巢卵泡液 (FF) 中有毒微量元素和抗氧化酶活性的变异性，并确定变异性的预测因素。第二个目标是试点家庭精浆（SP）采集并评估有毒微量元素的时间变化。 意义：拟议项目的结果将使我们能够修改计划中的更大规模研究的方案和分析策略，旨在更明确地调查微量有毒元素暴露对体外受精（IVF）结果和种族差异的影响。根据最近发布的 NHANES 数据，2011-2012 年亚洲人的有毒微量元素平均水平高于美国其他种族/族裔，包括 As、Cd、Pb 和 Hg。此外，在美国，亚洲女性的体外受精结果一直比白人女性差。受到越来越多关注的一种可能解释是，与饮食和健康行为相关的环境生殖毒物（包括有毒微量元素）的不同暴露。识别潜在可改变的有毒物质暴露对于设计干预措施以最大限度地提高体外受精活产的可能性或识别失败风险较高的夫妇是必要的。然而，进行体外受精的医生经常收集多个卵母细胞，产生多个胚胎，并根据临床因素进行移植，以最大限度地提高活产的可能性。因此，研究人员无法确保来自卵泡样本的卵母细胞被转移并导致妊娠和活产，因此无法直接将 FF 中测量的分析物浓度联系起来。我们小组和其他人的初步数据表明 FF 中有毒微量元素的卵泡间变异性，因此无法实施单卵泡妊娠/分娩研究设计可能会降低统计功效。在缺乏大量研究参与者的情况下，需要一种方法学解决方案。 创新：拟议的项目具有创新性，因为它是唯一一项表征 FF 中有毒微量金属变异性的研究，并评估其作为研究 IVF 结果的暴露生物标志物的效用。 方法：我们的美国研究人群中有近 1/3 由亚洲女性组成，因此我们将评估 IVF 程序正常临床背景下有毒微量元素的差异。我们将从我们中心招募 50 对 IVF 夫妇，并在卵母细胞取出过程中从四个单独的卵泡中收集 FF。我们将： 1) 测量 FF 中 As、Cd、Pb、Hg 和六种抗氧化酶活性的水平，以表征卵泡之间、卵巢之间、女性之间以及分析因素的变异来源； 2) 考虑 FF 体积、IVF 治疗方案、不孕症诊断、年龄、种族、体重指数、吸烟、鱼类消费和其他因素作为 FF 变异的预测因素； 3) 试点家庭精液标本采集策略，以评估 SP 有毒微量元素的纵向变化。研究团队丰富的合作经验和专业知识提高了成功的可能性。