CA 125 has been found in high concentrations in human amniotic fluid throughout gestation, with significant quantities seen in the decidua and chorion. Because disruption of the epithelial basement membrane of the fetal membrane or the decidua could theoretically lead to a rise in maternal CA 125 levels, this increase may be a predictor of subsequent spontaneous abortion of the fetus. A study was initiated to investigate whether a sudden rise in the serum CA 125 level might predict spontaneous first-trimester abortions. CA 125 levels of 101 pregnant women were evaluated 18-22 days from conception and 6 weeks from conception (a frequent time for spontaneous abortion) to determine whether there is a sudden increase (from baseline or early trimester levels) during the middle or late first trimester immediately before or at the time of abortion. The results indicated that although there was a definite correlation found between elevation of CA 125 and spontaneous abortion, the higher levels occurred early in the first trimester whereas the majority of abortions did not occur until much later, after fetal viability was established. Six of ten women with CA 125 levels of 150 U/mL or greater aborted, compared with four of 92 women with CA 125 levels less than 150 U/mL. One of 11 women pregnant after in vitro fertilization had a CA 125 level above 150 U/mL, and she aborted.