CD4⁺ CD25^bright regulatory T (T_reg) cells have been identified as a principle regulator of tolerance during pregnancy. In the setting of pre-eclampsia, however, little is known about the dynamics of these cells. In the current study, we determined CD4⁺ CD25^bright T_reg cells in the peripheral blood using flow cytometry and forkhead box P3 (FoxP3⁺) cells at the placental bed using immunohistochemical staining. Peripheral blood mononuclear cells (PBMC) of 38 pre-eclamptic cases (17 cases Japanese, 21 cases Polish), 40 normal late pregnancy subjects (20 subjects Japanese, 20 subjects Polish), and 21 non-pregnant healthy controls (10 subjects Japanese, 11 subjects Polish) were included. We found the percentage of CD25^bright cells within the CD4⁺ T cell population in PBMC was reduced significantly in both Japanese and Polish pre-eclamptic cases than in normal pregnancy subjects (P < 0·001) and non-pregnant healthy controls (P < 0·001). Also, the percentage of FoxP3⁺ cells within CD3⁺ T cells in the placental bed biopsy samples of pre-eclamptic cases were decreased compared to those in normal pregnancy subjects. These findings suggest that a decreased number of T_reg cells was present in pre-eclampsia, and these changes might break the maternal tolerance to the fetus.

Recurrent pregnancy loss is a common problem in the reproductive age population of women. It can be caused by many different conditions. This problem is addressed in international guidelines that take a slightly different approach to its diagnosis and treatment. The guidelines used in this review mainly use the guidelines of the Royal College of Obstetricians and Gynaecologists (RCOG), American Society of Reproductive Medicine (ASRM) and European Society of Human Reproduction and Embryology (ESHRE). This review shows how much the approach to miscarriages has changed and how much more needs to be explored and refined. The review also addresses the topic of unexplained pregnancy loss, which continues to be a challenge for clinicians.