Recurrent pregnancy loss (RPL) is one of the major concerns in Japan. We performed a long-term multicenter prospective study to reveal the risk factors and pregnancy outcomes of RPL in Japan. Antiphospholipid antibodies (aPL), malformation of the uterus, thyroid dysfunction, parental karyotype abnormality, factor XII deficiency, and protein S deficiency were defined as the risk factors of RPL. The prevalence of each risk factor was similar to previous studies except aPL positive rate. No risk factors were detected in more than half of RPL patients (65.2%). In transiently aPL-positive patients, the live birth rates with LDA were comparable to that with heparin + LDA. Despite that factor XII deficiency and protein S deficiency are not recognized as risk factors for RPL in general, low-dose aspirin (LDA) or unfractionated heparin + LDA therapy improved live birth rates. However, the live birth rate treated with LDA and that with unfractionated heparin + LDA were comparable in factor XII deficiency and protein S deficiency. Factor XII deficiency and protein S deficiency might be considered to be the risk factors of RPL and LDA therapy might be recommended in Factor XII deficiency, protein S deficiency, and transiently aPL-positive patients. We have discussed the risk factors and the live birth rate after treatment between Japan and worldwide.
