Recurrent miscarriage: current concepts in diagnosis and treatment

Abstract

Although recurrent miscarriage (RM) affects only 1-3% of couples, it has a major influence on the wellbeing and psychosocial status of patients. Therefore, research into improved diagnosis and development of new treatment strategies is essential. In this review, we summarize current concepts on diagnosis and treatment in RM, drawing upon research reports and international guidelines to provide insights into the pathophysiology of pregnancy disrupted by repeated miscarriage. Anatomical malformations, infectious diseases, endocrine disorders, autoimmune defects as well as acquired and inherited thrombophilia are established risk factors in RM. In addition, our recent findings indicate an impact on miscarriage incidence of glycoproteins such as glycodelin, and nuclear hormone receptors such as the peroxisome proliferator-activated receptors (PPARs). Significantly reduced glycodelin expression is associated with miscarriage, whereas up-regulation of PPARs appears to compensate for either the activated immune response or the disturbed cytotrophoblast differentiation in RM patients. There is also evidence that circulating placental microparticles are increased in a subgroup of RM patients, indicating an acquired procoagulant state even outside pregnancy. Treatment strategies like aspirin and low molecular weight heparin (LMWH) are standard medications in RM, although only a few placebo-controlled trials have proven their benefit in respect to live birth rate. There is emerging evidence that new treatment options, including drugs like TNFalpha inhibitors and granulocyte colony-stimulating factor (G-CSF) might be beneficial in some cases of RM. However, larger clinical trials must be completed to further prove or disprove benefits of these drugs in the treatment of RM patients.