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Factor V Leiden mutation in women with early recurrent pregnancy loss: a meta-analysis and systematic review of the causal association

Abstract

Background

Recently, the interest has focused on the increased prevalence of thrombophilic defects in women with gestational complications.

Objective

To explore whether women with early recurrent pregnancy loss (RPL) are at increased risk of being carriers of the Factor V Leiden (FVL) mutation compared to those who have a normal reproductive history.

Methods

A manual and electronic literature search was undertaken to identify studies with a case–control population of women with two or more first trimester RPLs of undetermined origin and age- and ethnicity-matched control group with normal reproductive history and at least one full-term delivery. Both groups were screened for FVL mutation. A quality assessment was performed according to the pre-established validity criteria and using the Cochrane handbook guidelines for observational studies. The combinability of studies was assessed by clinical and statistical methods (Breslow–Day’s test of homogeneity). Quantitative data were abstracted with regard to the prevalence of FVL mutation in the case and control group, and 2 × 2 tables were created. The ratio comparing the odds of FVL mutation in women with early RPL with the odds of FVL mutation in women with normal reproductive outcome was calculated with its 95 % confidence interval (CI) by Mantel–Haenszel method.

Results

Nine studies met the inclusion criteria and were selected for review. A total of 2,147 women were screened for the FVL mutation, 1,305 women with early RPL, and 842 women with no gestational complications. Women with early RPL had indeed a statistically significantly increased carrier frequency of FVL mutation, the common OR being 1.68 (95 % CI: 1.16–2.44).

Conclusion

FVL carrier state may increase the susceptibility for early RPL. Testing for FVL mutation should be considered in women with unexplained early RPL and thrombophylaxis has been suggested in women with unexplained RPL associated with FVL mutation.

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Fig. 1

Abbreviations

FVL:

Factor V Leiden

RPL:

Recurrent pregnancy loss

APC:

Activated protein C

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Acknowledgements

CS re-addressed specific questions, discussed in detail data, analysis, and results, and wrote the final draft of the manuscript. TAJ conceived the study, designed the study, analyzed data and results, and wrote the first draft of the manuscript. MW conceived the study and reviewed the paper. We are very grateful to the Saudi Cultural Bureau, Ottawa, ON, for the support of Dr. Al-Jishi.

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The authors declare that they have no conflict of interest.

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Sergi, C., Al Jishi, T. & Walker, M. Factor V Leiden mutation in women with early recurrent pregnancy loss: a meta-analysis and systematic review of the causal association. Arch Gynecol Obstet 291, 671–679 (2015). https://doi.org/10.1007/s00404-014-3443-x

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Keywords

  • Factor V Leiden
  • Recurrent pregnancy loss
  • Recurrent spontaneous abortions
  • First trimester
  • Thrombophilia
  • Coagulation defects