Preterm birth (PTB) is divided into spontaneous and artificial PTB, and spontaneous PTB (SPTB) occurs in about 70%. And history of SPTB itself is a risk factor for SPTB in next pregnancy. The rate of repeated SPTB in Japan is 22.3% according to a recent report. Although there are a lot of causes for SPTB, intra-uterine inflammation (histological chorioamnionitis: hCAM) is the main reason. So, intra-uterine inflammation/infection in preterm labor (PTL) is the most important marker as same as clinical symptom such as genital bleeding and maturation of cervix. In particular, super-infection (bacteria and Ureaplasma/Mycoplasma) in amnion is strongly related with earlier SPTB. According to the intra-amniotic environment of PTL, antibiotics and/or progesterone (17-α-hydroxyprogesterone caproate: 17OHP-C) are selected with maintenance tocolysis, and the pregnant period could prolong for about 4 weeks. However, in cases with severe intra-amniotic inflammation/infection, there is a limitation not to maintain the pregnancy period. Therefore, we need the strategy to prevent intra-amniotic inflammation and infection in high risk pregnancy for SPTB. The regulatory T cell that is an important role to maintain the pregnancy is associated with intestinal Clostridium. And in PTL patients, Clostridium in intestine was poor when the patients had SPTB. Therefore, the probiotics including Clostridium might be helpful to prevent recurrent SPTB.

HPV infection is the primary cause of cervical cancer and its precancer. With popularization of HPV prophylactic vaccines, the incidence of cervical cancer is expected to decrease, however, it will take time to eradicate cervical cancer. In order to prevent and control cervical cancer, it is important to implement a step-by-step preventive strategy according to the level of prevention: the primary prevention by HPV prophylactic vaccines; the secondary prevention by screening and treatment; and the tertiary prevention by the treatment of invasive cervical cancer. In this review, we especially focus on the secondary prevention and discuss the management of HPV-related cervical precancer based on the HPV genotypes as well as human immune responses against HPV infection.

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.