Thrombosis and Haemostasis, 2010; 103(2): 472–473
Authors: Pierpaolo Di Micco, Maristella D’Uva, Corrado Lodigiani, Lidia Luciana Rota
Affiliations:
- Thrombosis Center, Istituto Clinico Humanitas, Milan, Italy
- Division of Medicine, Fatebenefratelli Hospital of Naples, Italy
- Department of Human Reproduction, “Federico II” University of Naples, Naples, Italy
Correspondence: Pierpaolo Di Micco, MD, PhD (pdimicco@libero.it)
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The association between thrombophilia and female infertility due to pregnancy loss is well established, both for inherited and acquired forms. However, the link between thrombophilia and unexplained female sterility—especially in women with repeated in vitro fertilisation (IVF) and embryo transfer (ET) failures—remains controversial.
Some studies have reported associations between thrombophilia and/or hypofibrinolysis with repeated IVF failures, while others found no strong correlation. There is still no consensus regarding the role of thromboprophylaxis in improving IVF outcomes in these patients. A single IVF failure is already frequent (≈70% of cases) and often unrelated to thrombophilia or other diseases. The literature remains inconsistent due to differences in inclusion criteria, exclusion parameters, and ethnic backgrounds of study populations.
Although several studies have found a >50% rate of thrombophilic defects among women with repeated IVF failures, many did not achieve statistical significance compared to controls. For example:
- Simur et al. studied 51 women with ≥3 IVF-ET failures; 62% had thrombophilic defects, but without statistical significance.
- Martinelli et al. found 27% inherited thrombophilia in 162 women, again without significant difference.
- Vaquero et al. reported 24% thrombophilic women versus 20% in controls, non-significant.
Regarding acquired thrombophilia, Martinelli et al. found no difference in antiphospholipid antibodies, whereas Vaquero et al. (19% vs 0%) and Qublan et al. found significant increases in women with ≥3 failed IVF cycles. Qublan et al. also observed higher prevalence of inherited and combined thrombophilia (≥2 defects) in these patients. Azem et al. confirmed a higher frequency of inherited thrombophilic variants in women with ≥4 IVF-ET failures. Coulam et al. further noted increased rates of PAI-1 4G/5G variants, suggesting a possible role of hypofibrinolysis.
Recent data also implicate homocysteine and folate metabolism, including the MTHFR C677T gene polymorphism, in unexplained infertility and IVF-ET failure.
Given the heterogeneity of available data, thrombophilia’s role in IVF failure remains unresolved. Future studies should adopt uniform inclusion/exclusion criteria for patients and controls. Currently, no guidelines recommend thrombophilia screening for repeated IVF failures, though it is standard for recurrent miscarriage. Thrombophilia may be just one of several conditions (e.g., thyroid disease, chronic inflammation, recurrent infection) affecting IVF outcomes.
Ethnic and regional differences also complicate interpretation, as IVF access and the number of permitted cycles vary across healthcare systems and ethics boards.
Conclusion:
Further research should determine whether antithrombotic therapy—particularly low-molecular-weight heparin—can improve IVF outcomes in women with repeated failures and maternal thrombophilia.
References:
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- Simur A, Ozdemir S, Acar H, et al. Gynecol Obstet Invest 2009; 67: 109–112.
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