Selection of reproductive health end points for environmental risk assessment.

In addition to the challenges inherent in environmental health risk assessment, the study of reproductive health requires thorough consideration of the very definition of reproductive risk. Researchers have yet to determine which end points need to be considered to comprehensively evaluate a community's reproductive health. Several scientific issues should be considered in the selection of end points: the severity of the outcomes, with a trade-off between clinical severity and statistical or biological sensitivity; the relative sensitivity of different outcomes to environmental agents; the interrelationship among adverse outcomes; the baseline frequency of the adverse outcome; evidence from reproductive toxicology; and specificity of reproductive effects from the environmental agent. Simultaneously, practical concerns should be addressed: frequency of occurrence of an event and consequent statistical power to evaluate changes; frequency of prerequisites (e.g., pregnancy) that are necessary to be at risk; time and money resource requirements for measuring the outcome; amenability of the end point to retrospective measurement; and burden of measurement on the population being studied. In this article, we discuss these scientific and practical considerations and recommend that reproductive risk assessment include measures of fecundability (menstrual function, time to pregnancy), fetal loss (clinically recognized miscarriage), and infant health (birth weight, gestational age). Additional methodological research is needed to refine the array of reproductive health measures that need to be examined as a consequence of environmental exposures.