[Intravenous immunoglobulin (IVIG) as treatment for recurrent pregnancy loss (RPL)]

Miscarriages are the most common complication in human pregnancies. Recurrent pregnancy loss (RPL) could occur for several reasons, such as: immunological abnormalities of the pregnant women and chromosomal abnormalities of the embryo. There are several autoimmune characteristics for RPL, such as autoantibodies, and sometimes RPL are a symptom of an autoimmune disease. It is unclear whether the autoantibodies are the cause, the consequence or an artifact of the RPL. Intravenous immunoglobulin (IVIG) is a preparation made of purified plasma of thousands of healthy donors. Currently, IVIG is provided as a treatment for several autoimmune diseases. There are reports on a beneficial effect of IVIG for women with RPL of unknown reason. Some reports indicate a beneficial effect of IVIG independent of aspirin, as well as in artificial fertilization. Nevertheless, the efficacy of IVIG has yet to be established. Perhaps a certain sub-group should be defined of women who suffer from RPL and have greater odds for successful IVIG treatment. A sub-group analysis showed that, in secondary RPL, IVIG is more successful when provided after embryo implantation, whereas, in primary RPL, IVIG is better when provided prior to conceiving. Apart from the miscarriage type (secondary or primary) other factors that might influence the IVIG-treatment success were found: the number of previous miscarriages, the age of the pregnant women and the way IVIG is administrated. The mechanisms of action of IVIG in RPL are multiple, complex and not fully understood. IVIG therapy regulates the immune system in several mechanisms, in a way that might increase the survival rate of the embryo in the uterus and might decrease the odds of a miscarriage. For example, one of the main mechanisms of IVIG in RPL is down-regulation of natural killer cells (NK cells) activity and expression. This finding is of great importance because it has been reported that women who have never given birth and have high levels of NK cells in their peripheral blood have higher chances of pregnancy loss. In conclusion, IVIG is an immunomodulator that exerts its beneficial effects in multiple mechanistic ways acting together synergistically. IVIG is a potential treatment for women with RPL as a result of immunological abnormalities.