Recurrent Pregnancy Loss: Immunologic

The immune system evolved to protect the individual from non-self, genetically different, or allogenic tissue. Immunity can be either innate (in born) or adaptive (acquired) depending on the molecule causing an immune response (antigen). An immune response involves the production of either antibodies in what is termed a humoral response or soluble proteins called cytokines in what is termed a cellular response.

Before describing the potential but controversial immune mediated causes of recurrent pregnancy loss, it is important to realize that successful pregnancy does not depend on an intact fully functioning immune system. This is known because in both people and laboratory animals incapable of making antibodies (humoral immunity) can nevertheless have successful pregnancies. Similarly, successful births can also be accomplished in women with severe immune deficiencies and in laboratory animals that lack the capability of making either a humoral or cellular immune response.

The immunologic theory that has fulfilled most of the criteria for causality for recurrent pregnancy loss is that involving antiphospholipid antibodies especially anticardiolipin antibodies called the antiphospholipid syndrome. Whether they are causative, coincidental, or a consequence of pregnancy loss remains controversial. The precise mechanism of action of how pregnancy loss occurs in cases involving anticardiolipin antiboidies is thought to be related to thromobosis or clotting of blood vessels in the placenta. Loss in such cases generally occurs after the first trimester with the average time of loss being 20 weeks of gestation. The antiphospholipid syndrome is not a cause of infertility or early first trimester losses.

Other immune theories involving cellular immunity have been proposed but remain less well studied. It has been suggested that the immunosuppressive effects of progesterone within the uterus at the maternal-fetal interface are at least partially responsible for the immunologic acceptance of the genetically different fetus.