Immunology

The mechanisms of the immune system, which allow for the differentiation of self from nonself and which neutralize potentially threatening substances, can contribute to infertility.

Society for Assisted Reproductive Technology (SART) data has shown that the per-cycle success rate for in-vitro fertilization (IVF) has remained at 24%. Although there has been an increase in success when the cause is male factor infertility and intra-cytoplasmic sperm injection (ICSI) is implemented, the rate for women whose etiology is female organic pelvic disease has not changed. The reproductive autoimmune failure syndrome (RAFS), first described in 1988, is the association of pregnancy wastage, infertility and endometriosis with circulating autoantibodies. Patients with RAFS have polyclonal B-cell activation; that is, their antibody producing cells including those that manufacture autoantibodies are very active.

The pathophysiologic mechanisms that cause in-vitro fertilization failures are complex. Antiphospholipid antibodies (APA) play a central role in this process. Phospholipids are adhesion molecules -- they help cells stick to each other. At a very basic level, they help the fetus "stick" to the uterus. Antiphospholipid antibodies interfere with this process, so that the transferred fetus has difficultly implanting, i.e., attaching to the uterus. Furthermore, APA cause problems with uterine and placental blood flow, making the uterus unhealthy for successful implantation. Antinuclear antibodies (ANA) cause inflammation in various tissues, including the uterus. This inflammatory process prevents the uterus from being able to host a proper implantation. CD56+CD16+ natural killer cells (NK) cells normally kill cancer cells before they grow into large tumors. These cells may misinterpret the implanting fetus as a cancer and kill it too. It is believed that antithyroid antibodies are markers for polyclonal B-cell activation and do not have a direct effect on implantation or the fetus. Any patient who has antithyroid antibodies should be carefully evaluated for APA, ANA and increased NK cell number and/or activity. (Source: Reproductive Immunology Associates website, 2001)