METHODS FOR ASSESSMENT OF ENVIRONMENTAL HAZARDS

该项目的目标是开发和应用精辟、先进的 精子分析的实用方法，可用于 人类生育力及其扰动的分析和预测。这个 这项工作的重点和方向是需要应用这样的 以标准化形式对人类危害进行评估的方法 环境或工作场所可能出现的生殖健康问题。 拟议的研究具有技术组成部分，导致新的 生物统计学方法在基础生物医学中的应用 问题。第一个具体目标是巩固、优化，然后 标准化机器视觉技术(CASA-计算机辅助精子 分析)用于测量人类精子的运动和形态。它提高了 现有系统，通过优化准确度、精密度和生物学 他们测量的参数的相关性。通过这样做，它将 向所有感兴趣的人提供计算机代码和标准参考录像带 任何CASA系统的校准和质量控制实验室。这个 第二和第三个具体目标应用了这个新增加的力量 用于分析人类精液之间关系的先进技术 质量和繁殖力。分析策略并不是简单地描述 生育状况明确的男性的精液，但要发展出新的 预测未来生育可能性的数学关系 根据现在和过去的精液质量参数。是这样的 人际关系应该被证明是评估 对生育的危害的后果比传统使用的规范性 精液参数范围。未来将有三组男性 研究，然后综合结果：正常的人，代表 放弃避孕，寻求怀孕的普通人群 (特定目标2)；精液异常的不育症患者通过 传统标准(具体目标3)；以及有 传统的正常精液(特定目标3)。不孕不育者的妻子 患者将被临床评估为没有明显的 生殖功能障碍。所有这些男人的生育能力将会是 监测，早期自然流产的发生率将是 为第一组确定。具体目标2和3的结果将 在人类男性生育能力的一般评估中有明显的应用。 他们还将提供分析工具，这些工具可以立即合并 使用来自特定目标1的先进但简化的技术， 在危害人类生育能力的野外研究中的应用。

The goal of this project is to develop and apply incisive, advanced but practical methods for analysis of spermatozoa, which can be used in the analysis and prediction of human fertility and its perturbations. The focus and orientation of this work are motivated by the need to apply such methods, in a standardized form, to the evaluation of hazards to human reproductive health that may arise in the environment or the workplace. The proposed studies have technological components which lead to new biostatistical methodologies which are applied to basic biomedical questions. The first Specific Aim consolidates, optimizes and then standardizes the machine vision technology (CASA-computer-aided sperm analysis) used to measure human sperm motion and morphology. It improves existing systems, by optimizing the accuracy, precision and biological relevance of the parameters which they measure. In so doing, it will provide computer codes and standard reference videotapes to all interested laboratories for calibration and quality control of any CASA system. The second and third Specific Aims apply the increased power of this newly developed technology to analysis of the relationship between human semen quality and fertility. The analytic strategy is not simply to characterize the semen of men whose fertility status is well-defined, but to develop new mathematical relationships which predict the likelihood of future fertility on the basis of parameters of present and past semen quality. Such relationships should prove to be more incisive tools for assessing the consequences of hazards to fertility than the traditional use of normative range for semen parameters. Three groups of men will be prospectively studied, and the results then integrated: normal men, representative of the general population, who abandon contraception and seek to conceive (Specific Aim 2); infertility patients who have abnormal semen by traditional standards (Specific Aim 3); and infertility patients who have traditionally normal semen (Specific Aim 3). The wives of the infertility patients will have been clinically assessed to have no apparent reproductive dysfunction. The fertility of all these men will be monitored, and the incidence of early spontaneous pregnancy loss will be determined for the first group. The results of Specific Aims 2 and 3 will have obvious application in the general assessment of human male fertility. They will also provide analytic tools, which can be immediately combined with the advanced but streamlined technology from Specific Aim 1, to applications in field studies of hazards to human fertility.