METHODS FOR ASSESSMENT OF ENVIRONMENTAL HAZARDS

本项目的目标是开发和应用精辟的、先进的、但 精子分析的实用方法，可用于 分析和预测人类生育能力及其扰动。 的 这项工作的重点和方向的动机是需要应用这种 方法，以标准化的形式，以评估对人类的危害 环境或工作场所可能产生的生殖健康问题。 拟议的研究有技术组成部分，导致新的 生物统计学方法应用于基础生物医学 问题. 第一个具体目标是巩固、优化， 介绍了机器视觉技术（CASA-计算机辅助精子 分析）用于测量人类精子运动和形态。 它改善 通过优化现有系统的准确性、精密度和生物学特性， 它们所测量的参数的相关性。 在这样做时， 向所有感兴趣的人提供计算机代码和标准参考录像带 校准和质量控制的任何CASA系统的实验室。 的 第二个和第三个具体目标应用这个新的增加的力量， 研究人类精液和精子之间关系的技术 质量和生育率。 分析策略不仅仅是描述 男性的精液，其生育状态是明确的，但要开发新的 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。 等 关系应该被证明是更深刻的工具，评估 危害生育能力的后果比传统使用规范的后果 精液参数范围 三组男性将被前瞻性地 研究，然后将结果整合：正常男性，代表 一般人口，放弃避孕并寻求怀孕 （具体目标2）;不育症患者有异常精液， 传统标准（具体目标3）;和不孕症患者， 传统上正常的精液（特定目标3）。 不孕症的妻子们 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 监测，早期自发流产的发生率将 确定为第一组。 具体目标2和3的结果将 在人类男性生育力的一般评估中具有明显的应用。 他们还将提供分析工具，可以立即组合 凭借先进但精简的技术，从具体目标1， 在人类生育危害实地研究中的应用。

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.