Multiple Miscarriages Linked to Gene

From the WebMD Archives

July 30, 2001-- Having a baby seems like an impossible dream to women who have recurrent miscarriages. For about half of these women, doctors are able to identify a specific problem causing the miscarriages, such as infections, hormonal imbalances, or immune problems. And for some of these, there are possible treatments. For the other half, however, experts have found no explanation.

That is, until now.

Austrian researchers may have uncovered why some of these remaining women miscarry: It's genetic. Given this new finding, reported in the August issue of Human Reproduction, infertility experts can look for new treatments for this devastating problem.

"Usually miscarriage happens in about 10-20% of [women trying to have a baby], but when someone has three or more miscarriages, their chances of having another miscarriage are very high, ... from 30-50% or 60%," infertility expert Matan Yemini, MD, tells WebMD. He is co-director of Diamond Institute for Infertility and Menopause in Millburn, N.J., and was not involved in the study.

Study author Clemens Tempfer, MD, and colleagues from the department of obstetrics and gynecology at the University of Vienna School of Medicine in Austria, have linked recurrent, unexplained miscarriage to the specific gene variation, called NOS3. Women who carry this variation tend to produce less nitric oxide. In the uterus, nitric oxide causes blood vessels to expand, thereby improving blood flow to the uterus and to the growing fetus.

The researchers compared 105 who had recurrent miscarriages to 91 postmenopausal women who had given birth at least twice and never had a miscarriage. They found that the women who had miscarried were more likely to carry the NOS3 gene variation.

Interestingly, drugs that help improve blood flow to the uterus or decrease the likelihood of blood clotting are already used to treat recurrent miscarriage. This research helps explain why this approach works.

According to expert Andrew Toledo, MD, who also reviewed the study for WebMD, "most of us that do work in repetitive miscarriage have always felt that in unexplained couples, ... there must be a molecular, genetic component to this." Toledo, a partner at Reproductive Biology Associates in Atlanta, specializes in reproductive endocrinology, infertility, and recurrent miscarriage.


Both Yemini and Toledo agree that this research opens the door to potential new treatments for unexplained miscarriage. These treatments might target the NOS3 gene variation directly or focus on improving blood flow to the uterus.

Perhaps the most important aspect of this new research is that it offers hope for women who continually have miscarriages, adds Yemini.

"Often, you see women who have had three, four, or five miscarriages who say, 'I cannot handle it; I'm not going to try anymore'", he says. "On the other hand, you see patients who somehow manage to have the courage not to give up. The ones who don't give up, in my experience, eventually have babies. But sometimes it's a very long road."

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