Repeated Implantation Failure (RIF) and RecurrentPregnancy Loss (RPL): Immunological Aspects

Fetus is a semiallograft to maternal hos t, therefore immune toleranceis important to prevent fetus from rejection. However,immune activation also plays a role in placental developmentand fetal growth. Therefore, it is necessary to evaluate pregnancyin terms of the balance between immune activation andregulation. We have showed in a mouse sys tem that Tregs areessential for the success of allogeneic pregnancies at the timeof implantation. Interes tingly, paternal antigen-specific Tregs,induced by seminal plasma priming, are accumulated in regionallymph nodes of the uterus one day before implantation.We have shown in mice that immature DCs inducing toleranceinflux into the uterus from outside of the uterus and PDL۲-positive immunosuppessive DCs remaining in the uterus are increasedat implantation. We have shown that M۲ macrophagesincrease in the uterus at implantation and removal of M۲ macrophagesat implantation period Results in implantation failurein mice. Interes tingly, we also found that M۲ macrophages werereduced in the endometrium at implantation period in IVF failurenon pregnant cases. Thus, immunosuppressive drug, tacrolimusand high dose IVIG therapy, that increase Tregs, M۲macrophages and immature DCs may be effective in treatingimplantation failure where excessive inflammation is present.Recurrent pregnancy loss (RPL) is defined as a his tory of twoor more miscarriages, the rate of live births is low in cases offour or more previous miscarriages. In addition, there are manycases of unexplained RPL cases. We performed randomizedcontrolled trial of high dose IVIG therapy from ۴ to ۶ weeks ۶days ges tation in unexplained RPL patients with a his tory of ۴or more miscarriages.We found that IVIG therapy was particularly effective whenpatient had ۶ or more previous miscarriages and when therapywas s tarted before ۶ weeks of ges tation. Overall, immunologicaltreatment that takes into account the immune s tatus of eachcase of implantation failure and RPL is likely to be effective