Miscarriage, the commonest complication of pregnancy, is the spontaneous loss of a pregnancy before the fetus has reached viability. The term therefore includes all pregnancy losses from the time of conception until 24 weeks of gestation. Recurrent miscarriage, ... Miscarriage, the commonest complication of pregnancy, is the spontaneous loss of a pregnancy before the fetus has reached viability. The term therefore includes all pregnancy losses from the time of conception until 24 weeks of gestation. Recurrent miscarriage, defined as 3 or more consecutive pregnancy losses, affects about 1% of couples; when defined as 2 or more losses, the scale of the problem increases to 5% of all couples trying to conceive (summary by Rai and Regan, 2006). Pregnancy losses have traditionally been designated 'spontaneous abortions' if they occur before 20 weeks' gestation and 'stillbirths' if they occur after 20 weeks. Subtypes of spontaneous abortions can be further distinguished on the basis of embryonic development and include anembryonic loss in the first 5 weeks after conception (so-called 'blighted ovum'), embryonic loss from 6 to 9 weeks' gestation, and fetal loss from 10 weeks' gestation through the remainder of the pregnancy. These distinctions are important because the causes of pregnancy loss vary over gestational ages, with anembryonic losses being more likely to be associated with chromosomal abnormalities, for example. Possible etiologies for recurrent pregnancy loss include uterine anatomic abnormalities, cytogenetic abnormalities in the parents or fetus, single gene disorders, thrombophilic conditions, and immunologic or endocrine factors as well as environmental or infectious agents (summary by Warren and Silver, 2008).
Pihusch et al. (2001) studied clotting factors in 102 patients with 2 or more consecutive spontaneous abortions compared to 128 women without miscarriage and found that heterozygosity for the 20210G-A mutation of prothrombin was more common in patients ... Pihusch et al. (2001) studied clotting factors in 102 patients with 2 or more consecutive spontaneous abortions compared to 128 women without miscarriage and found that heterozygosity for the 20210G-A mutation of prothrombin was more common in patients with abortions in the first trimester (p = 0.027; odds ratio, 8.5). None of the patients had deficiencies of antithrombin, protein C, or protein S. Patients with elevated anticardiolipin antibodies were considered to have the antiphospholipid syndrome (107320) and were excluded from the study; patients with chromosomal abnormalities were also excluded. No relationship to recurrent spontaneous abortion was found with mutations in the other clotting factors studied, including factor V Leiden (612309.0001), the 677C-T mutation of MTHFR (607093.0003), the 1565C-T polymorphism of GP3A (173470.0006), and the -455G-A polymorphism of the FGB gene (134830.0008). Pihusch et al. (2001) noted that the prothrombin 20210G-A mutation causes only a moderately thrombophilic state, and in contrast to factor V Leiden, it is associated with problems of both the venous and arterial systems. In this respect, the 20210G-A mutation may resemble the antiphospholipid syndrome, which has been well documented to cause abortions as well as arterial and venous thromboses. Furthermore, in addition to fibrin generation, thrombin also activates tissue components represented in the placenta and induces cellular responses. Increased prothrombin levels may affect placental function by influencing pivotal mechanisms such as cell adhesion, smooth muscle proliferation, and vasculogenesis.