Multiple thrombophilic gene mutations rather than specific gene mutations are risk factors for recurrent miscarriage

Am J Reprod Immunol. 2006 May;55(5):360-8. doi: 10.1111/j.1600-0897.2006.00376.x.


Problem: Recurrent miscarriage is a heterogeneous condition. While the role of acquired thrombophilia has been accepted as an etiology of recurrent miscarriage, the contribution of specific inherited thrombophilic genes to this disorder has remained controversial. We compared the prevalence of 10 thrombophilic gene mutations among women with a history of recurrent miscarriages and fertile control women.

Method of study: A total of 150 women with a history of two or more recurrent pregnancy losses and 20 fertile control women with no history of pregnancy losses 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 prevalence of these mutations was compared between women experiencing recurrent miscarriage and controls.

Results: No differences in the frequency of specific gene mutations were detected when women with recurrent miscarriage were compared with control women. However, the prevalence of homozygous mutations and total gene mutations among patients with recurrent miscarriage was significantly higher than among controls. Homozygous mutations were found in 59% of women with a history of recurrent pregnancy loss contrasted to 10% of control women. More than three gene mutations among the 10 genes studied were observed in 68% of women with recurrent miscarriage and 21% of controls.

Conclusion: Inherited thrombophilias are associated with recurrent miscarriage. This association is manifest by total number of mutations rather than specific genes involved.

MeSH terms

  • Abortion, Habitual / blood
  • Abortion, Habitual / etiology*
  • Abortion, Habitual / genetics*
  • Abortion, Habitual / immunology
  • Adult
  • Antibodies, Antiphospholipid / blood
  • Blood Coagulation Factors / genetics
  • Case-Control Studies
  • Factor V / genetics
  • Female
  • Hemostasis / genetics
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Mutation*
  • Pregnancy
  • Prothrombin / genetics
  • Risk Factors
  • Thrombophilia / blood
  • Thrombophilia / complications*
  • Thrombophilia / genetics*


  • Antibodies, Antiphospholipid
  • Blood Coagulation Factors
  • factor V Leiden
  • Factor V
  • Prothrombin
  • Methylenetetrahydrofolate Reductase (NADPH2)