Immunotherapy not helpful to prevent miscarriage

July 31, 1999

A treatment commonly used by physicians around the world to prevent recurrent miscarriage was found to have no benefit, according to a study by led researchers at the University of Chicago, as reported in the July 31, 1999 issue of The Lancet.

"This is the largest, most comprehensive study of its kind to evaluate a costly and controversial therapy for miscarriage," said Carole Ober, PhD, lead author of the study and professor of human genetics and obstetrics and gynecology at the University of Chicago. "Many smaller studies have reported conflicting results, but this is the largest and first prospective, randomized, double-blind study and it clearly shows no benefit."

The Recurrent Miscarriage Study found that women treated with immunotherapy--also called paternal lymphocyte immunization, or mononuclear-cell immunization--had more and later miscarriages than those women who received a placebo.

Immunotherapy has been used in humans for more than two decades and is a costly treatment option offered in private physicians' offices and medical centers. During therapy the mother is injected with mononuclear cells prepared from the father's blood. The therapy is based on the belief that it offers a protective immune response and helps maintain the pregnancy.

Six medical centers from the United States and Canada participated in the Recurrent Miscarriage Study, evaluating 179 women from July 1992 through December 1997. The women, who had three or more previous unexplained miscarriages, were randomly assigned to a treatment or control group. Eighty-nine women were injected with blood cells from their male partners, and 90 women were injected with the same amount of a placebo (saline). All patients were contacted every three months to find out if they had become pregnant. If they did not become pregnant within six months they were re-immunized. All pregnant women were also given weekly ultrasounds and "tender loving care" (TLC) therapy during the first 12 weeks of pregnancy. Seventy-three percent, 131 of 179 women, conceived within 12 months of immunization. Of those who became pregnant, 37 women in the treatment group had miscarriages, compared with 22 women in the control group. In addition, the immunized women had miscarriages later in pregnancy. The mean interval between conception and miscarriage was 8.9 weeks in the treatment group and 6.2 weeks in the control group, and six of the treated women had miscarriages after 10 weeks gestation.

"We began the study to determine if immunotherapy was effective in preventing recurrent miscarriage," said Ober, "but it's surprisingly ineffective. The goal of any clinical research is to determine what treatment provides the best option for patients, and this therapy should not be used as a treatment for recurrent miscarriage."

An estimated 15 to 20 percent of all pregnancies result in miscarriage, making it the most common complication of pregnancy. Between one-half and one percent of couples experience recurrent miscarriage, defined as three or more fetal losses. Although there are many known factors that cause recurrent miscarriage (such as genetic and hormonal causes, uterine or cervical structural abnormalities, maternal disease, and infectious causes) it is possible to identify a factor in only about 50 percent of all cases.

An independent data monitoring and safety board kept track of all data for the study. In late 1997, after all patients had been enrolled, the board asked researchers not to immunize any more patients. A few patients, who still required follow-up immunization after six months of unsuccessful pregnancy, where not immunized a second time due to the non-beneficial results of the study.

The multicenter clinical trial was funded by a $2.2 million grant from the National Institutes of Health. Investigators include Ober, T. Karrison, PhD, R.B. Barnes, MD, B. Baron, MD, and M.A. Walker, MSN, from the University of Chicago; R.R. Odem, MD, J.R. Schreiber, MD, from Washington University; D.W. Branch, MD, J.R. Scott, MD, from the University of Utah; M.D. Stephenson, MD, from the University of British Columbia.

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