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）中有毒痕量元素和抗氧化酶活性的变异性，并确定可变性的预测指标。次要目标是在收集家用血浆（SP）进行验证并评估有毒痕量元素的时间变化。 意义：拟议项目的结果将使我们能够为计划的大型研究修改方案和分析策略，旨在更明确地研究痕量暴露对有毒元素对体外受精（IVF）结果和种族差异的影响。根据最近发布的NHANES数据，与2011 - 2012年其他美国种族/种族相比，亚洲人的毒性痕量要素的平均水平更高，包括AS，CD，PB和HG。此外，在美国，亚洲妇女始终表现出比白人女性的IVF结局差，一种可能受到关注的可能解释是对与饮食和健康行为相关的环境生殖有毒物质的差异暴露，包括有毒的痕量元素。为了设计干预措施，必须识别潜在的可修改毒物暴露，以最大程度地提高IVF现场出生的可能性或识别出高失败风险的夫妇。但是，进行IVF的医生通常会收集多个卵母细胞，从而导致多个胚胎，这些胚胎是根据临床因素转移的，以最大程度地提高活产的可能性。因此，研究人员无法确保从采样卵泡中的卵母细胞转移并导致怀孕和活产，因此无法直接连接FF中测量的分析物的浓度。来自我们小组和其他人的初步数据表明，FF中有毒痕量元素的流体间变异性，因此无法实施一个卵泡 - 一个妊娠/分娩研究研究设计可能会降低统计能力。在没有大量研究参与者的情况下，需要方法学解决方案。 创新：拟议项目具有创新性，因为它是表征FF中有毒痕量金属变异性并评估其用作研究IVF结果的生物标志物的唯一研究。 方法：在美国的研究人群中，将近1/3的研究人群由亚洲妇女组成，因此我们将评估在IVF程序正常临床背景下与有毒痕量元素有关的差异。我们将从中心招募50对IVF夫妇，并在卵母细胞检索期间从四个单独的卵巢卵泡中收集FF。我们将：1）测量FF中AS，CD，PB，HG和6种抗氧化酶活性的水平，以表征卵泡之间，卵巢，女性和分析因素之间的变异源； 2）考虑FF体积，IVF治疗方案，不育诊断，年龄，种族，体重指数，吸烟，鱼类消耗和其他因素作为FF变异性的预测因素； 3）试行家庭精液标本收集策略，以评估SP有毒痕量元素的纵向变化。研究团队的广泛协作经验和专业知识增强了成功的可能性。