Environmental Factors A variety of environmental factors have been linked to sporadic and recurrent early spontaneous pregnancy loss. These are difficult studies to perform, because, in humans, they all must be retrospective and all are confounded by alternative or additional environmental exposures. Nevertheless, the following factors have been linked to pregnancy loss: exposure to medications (e.g., antiprogestogens, antineoplastic agents, and inhalation anesthetics), exposure to ionizing radiation, prolonged exposure to organic solvents, and exposure to environmental toxins, especially bisphenol-A and heavy metals (296–299). The latter two exposures have been demonstrated to have both endocrine and immune effects that could lead to poor placentation and subsequent pregnancy loss (300,301). Associations between spontaneous pregnancy loss and exposures to video display terminals, microwave ovens, high-energy electric power lines, and high altitudes (e.g., ﬂight attendants) are not substantiated (302,303). There is no compelling evidence that moderate exercise during pregnancy is associated with spontaneous abortion. In the absence of cervical anatomic abnormalities or incompetent cervix, coitus does not appear to increase the risk for spontaneous pregnancy loss (304,305). Exposure to three particular substances—alcohol, cigarettes, and caffeine—deserves specific attention. Although some conﬂicting data exist, one very large epidemiologic study has shown that alcohol consumption during the first trimester of pregnancy, at levels as low as three drinks per week, is associated with an increased incidence of spontaneous pregnancy loss (306–308). Cigarette smoking has also been linked to early spontaneous pregnancy loss; however, this is also not without controversy (309–311). Alcohol and tobacco intake in the male partner correlates with the incidence of domestic violence, which in turn is associated with early pregnancy loss (312). Finally, recent evidence adds to a growing body of literature that suggests consumption of coffee and other caffeinated beverages during early pregnancy is linked to adverse pregnancy outcome (309,313). The most publicized recent report casts doubt on the definition of a lower limit for safe use of caffeine in the first trimester of pregnancy (309). Obesity, stress at work, and use of nonsteroidal anti-inﬂammatory agents during early pregnancy have all been linked to an increased rate of isolated spontaneous pregnancy loss (314–317).
Investigative measures that are potentially useful in the evaluation of recurrent spontaneous abortion include obtaining a thorough history from both partners, performing a physical assessment of the woman (with attention to the pelvic examination), and a limited amount of laboratory testing (Table 33.3).
History A description of all prior pregnancies and their sequence as well as whether histologic assessment and karyotype determinations were performed on previously aborted tissues are important aspects of the history. Approximately 60% of abortuses lost before 8 weeks of gestation were reported to be chromosomally abnormal; most of these pregnancies are affected by some type of trisomy, particularly trisomy 16 (318,319). The most common single chromosomal abnormality is monosomy X (45X), especially among anembryonic conceptuses (320). Aneuploid losses are particularly prevalent among women with recurrent pregnancy loss who are over the age of 35 (8). Although somewhat controversial, the detection of aneuploidy in miscarriage specimens may be less when the couple experiencing recurrent abortions is euploidic. Alternatively, some investigators have suggested that, because aneuploidy is common among miscarriage specimens from patients experiencing both isolated and recurrent spontaneous pregnancy losses, if aneuploidy is documented in fetal tissues from a recurrent pregnancy loss patient, this loss does not affect their prognosis for future pregnancy maintenance (13).