Molecular epidemiology: principles and practices. Schulte PA, Perera FP, eds. San Diego, CA: Academic Press, 1993 Apr; :385-406
Although most of the literature in reproductive epidemiology focuses on clinically recognized biological events, such as fetal loss or malformations, current and future studies are likely to involve a range of biologic markers, either as outcomes or to indicate exposure or susceptibility. Literature on effect markers such as semen analysis and early pregnancy loss is growing. Advances in molecular biology are providing new tools with which to investigate poorly understood disorders of reproduction. Wide-scale use of molecular genetic diagnostic tests is almost certain to be common in clinical medicine, yielding new insights into the etiology, mechanism, and risk of inherited conditions. Advances in DNA technology have allowed exploration of the previously speculative role of molecular mutation that results in germ line mutations, most likely leading to early pregnancy loss. Defects in genetic coding for products critical for embryonic or fetal development have been hypothesized to play a causative role in euploidic abortion in humans (Butler and McDonough,1989). The framework for employing biologic markers involves three separate but interlinked systems. A couple's reproductive success depends on a delicate physiochemical balance between and within the paternal, maternal, and fetal systems. Any disruption of this balance can result in a broad range of effects. The consequence of exposure of men and women to mutagens, teratogens, and carcinogens is described in Figure 15.1. Exposure of both genders may result in cancer or chromosomal damage, potentially increasing individual risk of cancer. Germ line mutation may lead to infertility, adverse pregnancy outcomes, or heritable alterations expressed in future generations.