Immunotherapy Doesn’t Reduce Risk of Recurrent Miscarriage

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Therapies to bolster a woman’s immune system response during pregnancy do not reduce the risk of miscarriage in women who have already had multiple miscarriages, according to a new review of recent studies.

The cause of most miscarriages is a mystery, but researchers believe that the immune system of some women may attack the foreign cells of an embryo or fetus. To prevent this attack, some women are “immunized” with white blood cells from their partner or intravenous antibodies before becoming pregnant, in an attempt to quiet any hostile immune response toward their pregnancy.

After reviewing four different types of immunotherapy, T. Flint Porter, M.D., of the LDS Hospital in Salt Lake City and colleagues conclude that none of these immunotherapies improve the chances of live birth among women who have miscarried several times previously.

These therapies should not be offered as treatment for unexplained multiple miscarriages, according to Porter, who said “women should be spared the pain and grief associated with false expectations that an ineffective treatment might work.”

The battery of immune system lab tests used to justify the immunotherapies “should be abandoned,” Porter added.

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The reviewers looked at studies of immunotherapy in women who had three or more prior miscarriages with no known cause. In 15 studies including 797 women, the women received transfusions of white blood cells from either their partners or a third person. In eight studies involving 303 women, the women received intravenous immune globulin antibodies. In a final study including 37 women, the women were treated with embryonic tissue called the trophoblast membrane.

There was no difference in the number of live births after 28 weeks of pregnancy between women treated with any of the therapies and women who received no treatment, Porter and colleagues found.

Dr. David Clark, an expert on the immunology of pregnancy at McMaster University in Hamilton, Ontario, said any review of immunotherapy for miscarriage should also consider whether the treatments were “given in an appropriate manner, and if patients unlikely to benefit from treatment were excluded” from the studies.

For instance, Clark said that white blood cells may have been improperly stored before transfusion in one of the studies examined by the Cochrane reviewers, which could have affected the cells’ potency.

Comparing the effectiveness of treatment doses between studies can also be a problem, Clark said. Since most immunotherapies involve whole tissues such as white blood cells and not purified hormones, it can be hard to measure and prescribe exact doses of the treatments, he said.

All these therapies are expensive and can carry the risk of serious side effects, including the risk of contracting hepatitis B or HIV and pregnancy complications, although these effects are rare, Porter and colleagues say.

In 2002, the Food and Drug Administration warned physicians that injectable white blood cell immune therapy is considered an investigational new drug not approved by the FDA.

Porter and colleagues say that few immunotherapy studies measure whether the treatment actually changes a woman’s immune system response. In any case, the exact immune cause of recurrent miscarriage, if one exists, is still unknown.

Future research should focus on diagnosing specific immune causes of miscarriage, and “a reliable method to determine which women might benefit from manipulation of the maternal immune system is urgently needed,” Porter said.

Porter TF, LaCoursiere Y, Scott JR. Immunotherapy for recurrent miscarriage. The Cochrane Database of Systematic Reviews 2006, Issue 2.

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