Intravenous Immunoglobulin (IVIg)
IVIg has been used to treat pre-implantation, peri-implantation and post-implantation recurrent pregnancy loss associated with elevated levels of antiphospholipid antibodies, antithyroid antibodies, circulating NK cells and NK cell killing activity and embryotoxins. It has also been used for treatment of unexplained recurrent pregnancy loss. The mechanisms by which IVIg works include:
- IVIg provides antibodies to antibodies (anti-idiotypic antibodies)
- IVIg suppresses B cells production of autoantibodies
- IVIg enhances regulatory T cell activity
- IVIg suppresses NK cell killing activity
Evidence from both animal and human studies suggest that intralipid administered intravenously may enhance implantation and maintenance of pregnancy. Intralipid is a 20% intravenous fat emulsion used routinely as a source of fat and calories for patients requiring parental nutrition. It is composed of 10% soybean oil, 1.2% egg yolk phospholipids, 2.25% gylcerine and water. Intralipid stimulated the immune system to remove “danger signals” that can lead to pregnancy loss. The appeal of Intralipid lies in the fact that it is relatively inexpensive and is not a blood product. Its likely benefit to IVF patients with immunologic dysfunction is under evaluation.
Low-dose aspirin (80mg or 1 baby aspirin) alone has used for treatment of recurrent post-implantation pregnancy losses. Among women with increased resistance of blood flow through their uterine arteries who were treated with aspirin for a minimum of two weeks, the pregnancy rate was increased from 17% to 47% after IVF/ET and the miscarriage rate decreased from 60% to 15%. As a prostaglandin inhibitor, aspirin would be expected to increase blood flow to the ovary prior to implantation, to the endometrium during implantation and to prevent clotting of the placental vessels following implantation. However, in studies of women experiencing recurrent post-implantation pregnancy loss/miscarriage associated with antiphospholipid antibodies, results of clinical trials have shown aspirin alone to be half as effective as other treatments including heparin and steroids. In two studies women receiving aspirin alone or heparin plus aspirin for treatment of repeat pregnancy loss associated with antiphospholipid antibodies, heparin plus aspirin provided a significantly better outcome that aspirin alone (live birth rate of 80% vs. 44%).
A rationale for the use of low-dose aspirin therapy during pregnancy for women with antiphospholipid antibodies is to decrease blood clots from forming in the placental vessels. The mechanisms by which aspirin prevents blood clots are through its antiprostaglandin and antiprostacyclin effects and inhibition of platelet adhesiveness and aggregation.