Diagnosis and treatment of recurrent miscarriage associated with immunologic disorders: Is paternal lymphocyte immunization a relic of the past?

Miscarriage is the most common complication of human pregnancy. Although the causes of recurrent miscarriage (RM) are various, immunologic aberrations between mother and fetus might be one of the causes of miscarriage. Immune responses fall into two categories: autoimmune and alloimmune. Currently, no appropriate diagnostic method has been established to identify alloimmune causes. We observed that NK cell activity in women with RM was higher than that in women without a history of miscarriage. Functional or quantitative analysis of NK cells could be used to identify alloimmune causes. Paternal lymphocyte immunization has been the most widely used treatment for alloimmune-mediated miscarriages. However, the latest Cochrane review by Scott reached the current conclusion that lymphocyte immunization therapy provided no significant beneficial effect over placebo in preventing further miscarriage. Approximately 70% of Japanese university hospitals are still performing paternal lymphocyte immunization. Is paternal lymphocyte immunization a relic of the past? Randomized controlled trials based on adequate patient selection in Japan should provide an answer to this question.