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

Gerhardt A, Scharf RE, Mikat-Drozdzynski B, Krüssel JS, Bender HG, Zotz RB

Department of Hemostasis and Transfusion Medicine, Heinrich Heine University Medical Center, Düsseldorf, Germany.

OBJECTIVE: To investigate whether sequence variants in the gene encoding for estrogen receptor alpha (ER-alpha) are risk determinants for fetal loss. DESIGN: Case-control study. SETTING: University medical center. PATIENT(S): 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. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The IVS1-401C/T polymorphism of the human ER-alpha, 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. RESULT(S): In the subgroup analysis of women with at least one late miscarriage (n = 70), the prevalences of the ER-alpha 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-alpha IVS1-401 T allele. CONCLUSION(S): Women with the IVS1-401 T allele of the ER-alpha and/or factor V Leiden are at increased risk for late fetal loss.

Published 2 August 2006 in Fertil Steril, 86(2): 448-53.
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