Pregnancy Failure and Heritable Thrombophilia

https://doi.org/10.1053/j.seminhematol.2007.01.005Get rights and content

Heritable thrombophilia is associated with an increased risk for pregnancy failure, defined as sporadic and recurrent miscarriage, late fetal loss, and other vascular pregnancy complications such as preeclampsia and intrauterine growth retardation. The pathogenesis is likely to include effects on trophoblast differentiation and not solely hypercoagulability. This is in line with the observation that most recurrent miscarriages occur early. Therapeutic options include aspirin as well as low-molecular-weight heparin. However, in women with heritable thrombophilia and unexplained recurrent pregnancy loss, evidence is not available as published trials have not used an adequate comparator (no treatment or placebo). Currently, randomized controlled trials with no treatment or placebo are being carried out and results should be awaited before implementing a potentially harmful intervention in pregnant women with heritable thrombophilia and a history of pregnancy failure.

Both infertility and pregnancy failure are extremely distressing for couples with the desire to have children. Pregnancy failure comprises (recurrent) early miscarriage, as well as late pregnancy loss. The role of heritable thrombophilia in pregnancy failure is reviewed, with a focus on recurrent miscarriage, in terms of epidemiology, etiology, and potential therapeutic implications.

Section snippets

Definition of Pregnancy Failure

The various forms of pregnancy failure have not been defined consistently. Recently, a revision of the nomenclature of early pregnancy events was proposed that applies ultrasound imaging for accurate clinical assessment and diagnosis.17 Fetal loss is defined as the previous identification of crown-rump length and fetal heart activity followed by loss of heart activity. Recurrent miscarriage is defined as three early consecutive losses or two late pregnancy losses. Early miscarriage comprises

Antiphospholipid Antibody Syndrome

In women with recurrent miscarriage due to the antiphospholipid antibody syndrome, a landmark randomized controlled trial showed an absolute increase of live birth rate from 41% to 72% with the use of a combination of low-dose unfractionated heparin and low-dose aspirin, as compared to aspirin alone.31 A second randomized trial in which low-molecular-weight heparin was added to aspirin did not demonstrate benefit of this combination therapy, with live birth rates of 72% and 78% in both

Conclusions

Pregnancy failure and other vascular pregnancy complications are associated with the presence of acquired or heritable thrombophilia. Pathogenic mechanisms are likely to include effects on trophoblast differentiation and not solely hypercoagulability. Current guidelines recommend a combination of low doses of aspirin and heparin in women with antiphospholipid syndrome and recurrent fetal loss, although these are not based on a wealth of high-quality evidence. For women with heritable

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