I've had 12 losses after a normal full-term first pregnancy. Is there any successful treatment for someone with an immunological problem (a person who is a candidate for IViG and immunization) once she finds out she's pregnant?

-- Leslie

Immunological causes for recurrent pregnancy loss are controversial. Data conflict, and there is little agreement among physicians as to the best approach.

There are two theories on how the immune system might interfere with the success of your pregnancy. The first relates to phospholipids -- compounds that are involved with embryo attachment and growth of the placenta and also help form blood vessel walls. Some women make antibodies against these vital compounds. These women either have difficulty conceiving or miscarry in the second or third trimester of pregnancy. If found, these antibodies are best treated with daily injections of heparin and baby aspirin.

The second theory involves the immune system's natural killer (NK) cells, special white blood cells that stand guard against invasion by foreign cells. Each cell in the body wears a protein "name badge" that helps NK cells identify it as friend or foe. These markers are called HLA. Most cells come with many HLA markers, such as HLA-A, -B, -C, -DR, and -DQ. However, the cells of a developing embryo's placenta do not show the usual markers found on other body cells. Most placental cells show the HLA-G marker. This indicates that the placenta is friend, not foe, and therefore should not be attacked.
Normally, when the embryo comes along looking for a site to implant and set up shop, NK cells that line the uterus are indifferent to the presence of the embryo. Sometimes, though, they are stimulated to become active and multiply, and they attack the placental cells. Doctors have several theories as to why this might happen. For instance, some placental cells may not have the appropriate HLA-G marker, or some NK cells may not recognize the marker.

Several treatments are used to try to suppress the NK cells. One procedure is to immunize the woman using the baby's father's white blood cells. Another is to infuse a protein solution of antibodies called IViG, which may either block sites on the placenta and mask them from attack, or attach to the NK cells and quiet them. The NK cells also have receptors for the hormone progesterone. When progesterone levels are sufficiently high, the hormone attaches to the NK cells and suppresses their action. Progesterone levels normally rise in pregnancy; if this mechanism is not working well, doctors can help the process along by giving high doses of progesterone.

Still, there is little agreement as to which treatment to block NK cells is the best -- or whether any of them work at all. Nor is there agreement on the best way to test to find out whether a pregnancy is at risk of immune-system attack. In fact, experts do not even agree whether this condition really exists. As diagnosis and treatment for these supposed conditions are exorbitantly expensive, one must carefully read all the evidence available and consider a second opinion before entering into an expensive controversial therapy.