According to the results of the present study, CD with the presence of a cluster or a number of plasma cells was frequently found when a CE patient became pregnant and miscarried. This suggested that inflammation in the endometrium remains in the decidua of some cases of miscarriage.
CD is pathologically diagnosed with the presence of plasma cells within the decidua (decidual endometrium). Although studies of CD in preterm and/or term pregnancy have been reported [20, 23], there have been no reports of CD in early-stage pregnancy. Therefore, there are no diagnostic criteria for CD in early pregnancy. Gilmore et al. pointed out that the histologic diagnostic criteria for CE differ from the literature and used a semiquantitative scoring system to avoid these problems . They divided the status into 4 grades: grade 0, no plasma cells seen; grade 1, rare single plasma cells; grade 2, rare clusters or more than 5 single cells total; and grade 3, many plasma cells with more than 5 clusters. In the present study, CD for the specimens of miscarriage cases was classified based on the report by Gilmore et al. That is, Non CD was defined as no plasma cells seen, and CD was divided into 3 grades: grade 1, 1 to 5 plasma cells in 10 HPFs; grade 2, rare clusters or 5 to 20 plasma cells in 10 HPFs; and grade 3, 20 or more plasma cells with more than 5 clusters in 10 HPFs. It was found that there were no significant differences in the incidence of CD of Grade 1, Grade 2, Grade 3, or Grade 1 + Grade 2 + Grade 3 between the Non-CE and CE groups. However, there was a significant difference in the incidence of Grade 2 + Grade 3 CD. In addition, although the number of cases was small in this study, Grade 2 or Grade 3 CD was not seen at all in Non-CE patients. In general, the number of immune cells per area is considered to be correlated with the degree of histological inflammation. Thus, our results suggested CD with moderate or higher inflammation was observed only in CE patients.
The association between CE and habitual abortion has been reported [8, 10]. Considering these clinical data and the fact that there is a higher incidence of CD when CE patients miscarry, CD appears to be related to miscarriage.
Plasma cells, which are the basis of the diagnosis of CD, produce the antibody for some kind of antigen. In patients diagnosed with CD in the present study, maternal immunity may have reacted to the chorionic tissue (placental tissue) as an antigen during the course of miscarriage. Grade 1 CD was found in 4/13 Non-CE patients who miscarried. Such a histologically mild degree of CD may have been due to miscarriage.
In the total cases of Grade 2 and Grade 3 CD, the incidence of CE before the pregnancy was 100%. Thus, when Grade 2 or Grade 3 CD is found in the miscarriage tissue, it means that CE existed before pregnancy in all cases, although the number of samples was low in the present study. Specimens from miscarriage cases have been used to confirm the presence of chorionic tissue and the exclusion of chorionic diseases such as molar pregnancy. If specimens obtained from a patient who miscarried are examined for the presence of CD, this may provide a clue regarding the presence of CE before the pregnancy, which may be useful for the subsequent fertility treatment.
To the best of our knowledge, this is the first study in the world to study the relationship between CE and CD in miscarriage specimens in order to investigate the direct effects of CE on pregnancy. Currently, when diagnosed as CE, the patient is usually treated with antibiotics and then undergoes embryo transfer. When the present study was conducted, it was already beginning to be thought that antibiotics might be effective to improve clinical outcomes. The patients in the CE group extracted for the present study were those who did not want antibiotic treatment. In this sense, the cases who became pregnant but miscarried following their diagnosis with or without CE are few and extremely valuable. Furthermore, the miscarriage specimens of these patients were even more valuable, and the results of the analysis of the miscarriage specimens could be compared with the presence or absence of CE. This is the strength of the present study.
On the other hand, although the numbers of cases and controls satisfied the power analysis, they were relatively small. Patients who sought antibiotic treatment were treated with them and excluded from the study. Though this attitude is ethically correct, this means that the CE group did not reflect all CE patients in the study period. These are the limitations of the present study.
In the future, it is important to investigate the effects of antibiotic treatment for CE on the incidence of CD in this area of research. In addition, conversely, it is very important to study whether a patient diagnosed with CD in a miscarriage will subsequently be diagnosed with CE.
We hope that this research provides new insights into the relationships among CE, CD, and miscarriage.