Expensive immunotherapy shows no advantage over placebo for recurrent miscarriage patients

August 25, 2010, University of Chicago

(PhysOrg.com) -- The University of Chicago Recurrent Pregnancy Loss Program (RPL) recently completed a comprehensive study examining the use of immunotherapy to help couples that had experienced recurrent miscarriages for unexplained reasons achieve a successful pregnancy.

Miscarriage is the most common complication of pregnancy, impacting 15 percent to 20 percent of all clinical pregnancies. About 1 percent of couples experience recurrent miscarriage, defined as three or more miscarriages before 20 weeks of pregnancy.

Causes of recurrent miscarriage can be identified in about half of the cases. The other 50 percent of couples have unexplained recurrent miscarriage, meaning genetic, hormonal and other causes have been ruled out. An immunological cause has been suggested for more than 80 percent of unexplained recurrent miscarriages.

Intravenous immunoglobulin (IVIG) consists of antibodies produced by that help fend off bacteria, viruses and other foreign bodies. Pooled from highly purified human plasma, IVIG is costly to process and, like all blood products, is not without risk. It is successfully used to treat immune disorders such as lupus, and other rheumatic diseases, and administered intravenously in a hospital setting. The University of Chicago Medical Center, along with six other medical centers in the United States and Canada, wanted to see if IVIG would suppress the mother's adverse immunological responses to pregnancy and overcome miscarriage.

The study led by Mary Stephenson, MD, director of the University of Chicago Recurrent Pregnancy Loss Program, to be published in the September 9, 2010 issue of , reported the largest to date evaluating the use of IVIG in couples with unexplained recurrent miscarriage. Eighty two women were randomized to either IVIG or saline, an inactive substance (placebo). The women were 18 to 44 years of age and had had one successful live birth followed by at least three unexplained consecutive miscarriages, all with the same partner. Known causes of recurrent miscarriage were ruled out.

The results showed no significant difference between the live birth rate for women receiving IVIG (70 percent) and women receiving the placebo (67 percent). The study's results were then combined with two smaller randomized trials, and again, no treatment benefit from IVIG was found.

Interestingly, 94 percent of women in both the IVIG and control groups had a live birth in the study, following an ultrasound at 6 weeks which revealed an embryo with cardiac activity. The impressive results are due to the supportive services offered, consisting of weekly blood tests in early pregnancy, close ultrasound monitoring and nurse contacts throughout the pregnancy, along with around-the-clock access to a RPL physician or nurse, according to Stephenson, professor of obstetrics and gynecology, University of Chicago.

In 2006, 42-year-old Teri Neri heard about Stephenson and the University of Chicago Recurrent Pregnancy Loss Clinic and joined the study. Neri and her husband Nick appreciated this high level of monitoring during the first trimester, which was a very frustrating and anxious time for them. "We had been trying for seven years to have a child after our son Nicholas was born," Teri said. "The sense of comfort the program gave us, along with peace of mind in knowing we were doing everything possible once I got pregnant (after four months) to ensure I'd carry the baby to term, made a real difference in my pregnancy. You could tell they really cared about us. And if I hadn't gotten pregnant, we'd at least get to the bottom of it (the miscarriages)."

Given the cost of IVIG (as much as $5,000 per dose outside the trial) and concern about its safety and effectiveness, the therapy has been controversial for years. "Prior studies had suggested that IVIG may have a role to play in recurrent miscarriage," said Stephenson. "Given this devastating reproductive problem, and the possibility of finding an effective treatment, I designed a study to answer the question whether IVIG is effective in improving the rate in couples who suffer from secondary recurrent miscarriage. With the risks associated with using a blood product, although it is highly purified and virally-inactivated, as well as the costs involved -- not usually covered by insurance -- this study sought to give a definitive answer."

At her fifth month of pregnancy, Teri's obstetrical care was transitioned to her local Ob/Gyn. "Our beautiful son Luke was born a few months later. Stephenson and all the others truly helped Nick and me realize a huge dream," in having a second successful pregnancy, she said.

The study was randomized and double-blinded, meaning the women were given either IVIG or a placebo by chance and neither the women nor the researchers knew who received which until after the study was completed. Patients were able to re-enter and receive the alternate infusion if they had another miscarriage, which ensured if the IVIG was of value that all participants had an opportunity to receive IVIG.

The infusions were started in a cycle in which the woman wished to conceive. Once pregnant, the woman received the same infusion every four weeks through the second trimester.

"Recurrent miscarriage is an emotionally draining and frustrating reproductive problem for couples," Stephenson said. "We are pleased to have completed a definitive trial to assess the impact of using IVIG. Although the trial found that IVIG is not useful, preconception evaluation and frequent ultrasound monitoring and supportive care in the first trimester was found to be highly effective. Therefore, IVIG should be abandoned for unexplained secondary recurrent miscarriage and further research is needed to understand how close monitoring improves outcome."

The study, which spanned more than ten years, was initially funded by a grant from, and IVIG supplied by the Canadian Blood Services. Subsequent funds and IVIG were provided by a University of Chicago Clinical and Translational Science Award, a University of Tennessee National Center for Research Resources Award and Talecris BioTherapeutics. Stephenson and her co-investigators declare no conflicts of interest.

More information: Paper: humrep.oxfordjournals.org/cgi/ … t/abstract/25/9/2203

Related Stories

Recommended for you

Best of Last Year—The top Medical Xpress articles of 2017

December 20, 2017
It was a good year for medical research as a team at the German center for Neurodegenerative Diseases, Magdeburg, found that dancing can reverse the signs of aging in the brain. Any exercise helps, the team found, but dancing ...

Pickled in 'cognac', Chopin's heart gives up its secrets

November 26, 2017
The heart of Frederic Chopin, among the world's most cherished musical virtuosos, may finally have given up the cause of his untimely death.

Sugar industry withheld evidence of sucrose's health effects nearly 50 years ago

November 21, 2017
A U.S. sugar industry trade group appears to have pulled the plug on a study that was producing animal evidence linking sucrose to disease nearly 50 years ago, researchers argue in a paper publishing on November 21 in the ...

Female researchers pay more attention to sex and gender in medicine

November 7, 2017
When women participate in a medical research paper, that research is more likely to take into account the differences between the way men and women react to diseases and treatments, according to a new study by Stanford researchers.

Drug therapy from lethal bacteria could reduce kidney transplant rejection

August 3, 2017
An experimental treatment derived from a potentially deadly microorganism may provide lifesaving help for kidney transplant patients, according to an international study led by investigators at Cedars-Sinai.

Exploring the potential of human echolocation

June 25, 2017
People who are visually impaired will often use a cane to feel out their surroundings. With training and practice, people can learn to use the pitch, loudness and timbre of echoes from the cane or other sounds to navigate ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.