Maternal IVS1-401 T allele of the estrogen receptor α is an independent predictor of late fetal loss

To investigate whether sequence variants in the gene encoding for estrogen receptor α (ER-α) are risk determinants for fetal loss. Case–control study. University medical center. One hundred four women with a history of fetal loss and 277 healthy women with at least one previous pregnancy and no previous fetal loss. None. The IVS1-401C/T polymorphism of the human ER-α, the G1691A mutation of the factor V gene (factor V Leiden), the G20210A mutation of the prothrombin gene, and the C677T polymorphism of the methylenetetrahydrofolate-reductase (MTHFR) gene were determined by polymerase chain reaction. In the subgroup analysis of women with at least one late miscarriage (n = 70), the prevalences of the ER-α IVS1-401 T allele (T/T vs. C/C, odds ratio [OR]: 2.85, P=.018; T/T + C/T vs. C/C, OR: 2.28, P=.043) and of heterozygous factor V Leiden (OR, 3.2; P=.002) were significantly higher among women with late fetal loss than among healthy women. Carriers of both risk determinants have an at-least additive increase in risk for late abortions (OR, 7.0; P=.0004). The population of all late abortions that would be attributable to the genetic variants (population attributable risk) was 13.9% for factor V Leiden and 49.2% for the ER-α IVS1-401 T allele. Women with the IVS1-401 T allele of the ER-α and/or factor V Leiden are at increased risk for late fetal loss.