Immunologic testing identifies immunologic factors contributing to recurrent pregnancy loss. The immune system of the body detects and attacks things that are different (non-self). Research in this area has led to a greater understanding of pregnancy losses that were previously classified as unexplained. Reproductive immunology is a new field in which few mechanisms to explain the causes of recurrent pregnancy loss are investigated and treated.
Immunologic causes of recurrent pregnancy loss or failure can be treated with immunotherapy. Various forms of immunotherapy have been introduced to treat couples experiencing recurrent pregnancy loss. Understanding the mechanisms involved in recurrent pregnancy loss allows a more focused approach to specific treatment.
Recurrent pregnancy loss is a healthcare concern that needs effective treatment. Before effective treatment can be instituted, a diagnosis must be made. The most common causes of recurrent pregnancy losses are chromosomal abnormalities within the pregnancy itself and immunologic risk factors within the uterus or the environment in which the pregnancy grows. Immunologic causes of occult pregnancy losses are different from early and late pregnancy losses. Once an accurate diagnosis is made and appropriate immunotherapy administered, a live birth rate of 70 to 80 percent can be expected.
Tests for Recurrent Pregnancy Loss (RPL) include:
Antiphospholipid Antibody (APA) — Tests for APA, which has been shown to have a direct effect on blood vessels as well as placental cells (trophoblasts) and preimplantation embryos. APA causes clotting in placental blood vessels, which can result in placental insufficiency and subsequent pregnancy wastage.
Antinuclear Antibodies (ANA) — Tests for ANA, which has been shown to have a direct toxic effect on preimplantation embryos. The frequent association of the presence of elevated APA and ANA in the same individual can be explained by the recently proposed hypothesis that they result from antibodies being formed to cell products after cell death.
Antithyroid Antibodies (ATA) — Tests for ATA, which is associated with an increase in the pro-inflammatory cytokines that are secreted by T cells within the uterine lining. Thus, the presence of ATA may represent a marker of an underlying T cell dysfunction that directly affects implantation.
Lupus Anticoagulant, Embryo Toxicity Assay (ETA) — ETA tests detect factors that kill embryos. Circulating embryotoxic factors have been associated with recurrent pregnancy loss, unexplained infertility, in vitro fertilization failure, and infertility associated with endometriosis.
Natural Killer Cell Activity — A reproductive immunophenotype measures the circulating percentages of natural killer (NK) cells. Elevated percentages of circulating NK cells predict loss of a chromosomally normal pregnancy. NKA assays evaluate the killing function of circulating NK cells as well as the ability of intravenous immunoglobulin (IVIg) to suppress that activity.
Treatments for recurrent pregnancy loss have included aspirin, heparin, glucocorticoids, intravenous immunoglobulin, all four, or a combination of two or three of these:
Prednisone and aspirin — Historically, recurrent pregnancy loss associated with antiphospholipid antibodies was treated with combinations of prednisone and aspirin. The rationale for prednisone therapy is suppression of autoantibodies such as antiphospholipid and antinuclear antibodies.
Intravenous immunoglobulin — Intravenous immunoglobulin (IVIg) therapy has been used as treatment for recurrent pregnancy loss associated with antiphospholipid antibodies, elevated circulating NK cells and embryotoxins, and abnormal NK cell activity as well as unexplained recurrent spontaneous abortions.
The usual dosage of IVIg for treatment of recurrent pregnancy loss is 25 grams but successful pregnancies have been reported using dosages from 20 to 60 grams. The half-life in circulation is 28 days so infusions are usually given every 28 days. Depending on the obstetric history, IVIg is continued every 28 days for a total of four to five monthly treatments for patients with a history of first trimester pregnancy losses. Women with a confirmed history of late pregnancy losses may be treated until 28 to 32 weeks gestation. Pregnancies may be monitored with immunologic blood tests and treatment may be modified based on the results of the blood tests.