Active or passive immunization in unexplained recurrent miscarriage

Controversy exists as to whether active immunotherapy with allogeneic lymphocyte transfusions (ALT) or passive immunotherapy with intravenous immunoglobulin (IvIg) improve the chance of live birth in women with unexplained recurrent miscarriages (RM). Meta-analyses of the placebo-controlled trials carried out as Cochrane reviews have concluded than none of the different forms of immunotherapy has proved effective in the total RM population. However, the included trials have generally been small and very heterogenous with respect to the clinical histories of patients and the immunization protocols. Thus, other meta-analyses which have looked at the efficacy in subgroups of RM patients have reported that ALT and IvIg may be effective in women with primary RM and secondary RM, respectively. In RM clinics in Denmark, ALT with donor lymphocytes or IvIg immunotherapy have been tested in several placebo-controlled trials since 1986 in which greater doses than used in other trials have been administered, and both treatments are now used for routine therapy. Our results have convinced us that using the correct immunization protocols on the right subsets of RM patients is effective, but we admit that new placebo-controlled trials focusing on subsets of RM patients are now urgently needed. Furthermore, treated patients should be extensively monitored for changes in a series of immune parameters that may predict pregnancy success and be of importance for our understanding of the mechanisms of action of immunotherapy in RM.