Objective:  We have previously reported that when 10 thrombophilic genes were investigated, more than three gene mutations among the 10 genes were observed significantly more frequently among women experiencing recurrent pregnancy loss than fertile control women. The question then arose as to which of the 10 mutations were necessary to identify the risk of recurrent pregnancy loss. The present study was undertaken to answer this question.

Materials and Methods:  550 women with a history of recurrent pregnancy loss had buccal swabs taken for DNA analyses of 10 gene mutations (Factor V G1691A, Factor V H1299R (R2), Factor V Y1702C, Factor II Prothrombin G20210A, Factor XIII V34L, beta-Fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b (L33P), MTHFR C677T, MTHFR A1298C). The frequency of these mutations were compared with controls published in the literature.

Results:  When examined individually, three out of the ten mutations studied correlated significantly with recurrent pregnancy loss compared with controls, including PAI-1 4G/5G (P = 0.0037), Factor XIII V34L (P < 0.0001), and homozygous MTHFR C667T (P = 0.04). The frequency of the Factor V Y1702C mutation was extremely low in patients and controls; thus, this gene was removed from further calculations. The remaining six mutated genes, when analyzed cumulatively, also corresponded with recurrent pregnancy loss with total number of mutations significantly increased among patients compared with controls (P < 0.0001).

Conclusion:  A panel of thrombogenic gene mutations consisting of Factor V G1691A, Factor V H1299R (R2), Factor II Prothrombin G20210A, Factor XIII V34L, beta-Fibrinogen-455G>A, PAI-1 4G/5G, HPA1 a/b (L33P), MTHFR C677T, and MTHFR A1298C can identify individuals at risk for recurrent pregnancy loss.