Article Text

  1. J. Munjal,
  2. L. Rovner,
  3. S. Gogineni,
  4. T. Tracy,
  5. P. Wang,
  6. C. J. Glueck
  1. The Jewish Hospital, Cincinnati, OH.


Background The propensity to form thrombi is physiologically increased in normal pregnancy secondary to reduction in naturally occurring anticoagulants, an increase in coagulation factors, and a reduction in fibrinolysis. We hypothesized that when the physiologic hypercoagulability of pregnancy is superimposed on the thrombophilic G1691A factor V Leiden mutation, sporadic first-trimester miscarriage and repetitive pregnancy loss are promoted. We hypothesized that the thrombophilic G1691A factor V Leiden gene mutation was a common, significant, treatable cause of sporadic first-trimester miscarriage.

Methods We compared the frequency of the G1691A factor V Leiden mutation in women with ≥ 1 pregnancy and 1 miscarriage with women having ≥ 1 pregnancy and 0 miscarriages. In 848 Caucasian women with consecutive measures of the factor V Leiden mutation, we compared the frequency of the V Leiden mutation in 136 women with ≥ 1 pregnancy and 1 miscarriage (260 live births, 136 miscarriages), 50 women with ≥ 1 pregnancy and 2 miscarriages (83 live births, 100 miscarriages), 53 women with ≥ 1 pregnancy and ≥ 3 miscarriages (recurrent pregnancy loss) (109 live births, 227 miscarriages), and 609 women with ≥ 1 pregnancy and 0 miscarriages (1,473 live births). We used PCR techniques to characterize the thrombophilic G1691A V Leiden [FV] gene mutation.

Results Of the 609 controls, 41 (6.7%) had FV heterozygosity versus 15 heterozygous and 2 homozygous FV cases (17 of 136, 12.5%) with 1 sporadic miscarriage, Χ3 = 5.2, p = .023, vs 8 of 53 (15%, 7 heterozygous and 1 homozygous) with ≥ 3 miscarriages, Fisher's p = .048, vs 2 of 50 (4%) with 2 miscarriages. The V Leiden frequency in cases with 1 sporadic miscarriage (17 of 136, 12.5%) did not differ from recurrent pregnancy loss cases with ≥ 3 miscarriages (8 of 53, 15%), Χ2 = 0.22, p = .64.

Conclusions After unexplained sporadic first-trimester miscarriage, as well as after recurrent pregnancy loss, to provide the option to prospectively optimize subsequent live birth outcomes with low molecular weight heparin throughout pregnancy, we suggest that measurements be done of the FV mutation, a treatable etiology for sporadic miscarriage, as well as for recurrent pregnancy loss.

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