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Articles about Infertility

| Unexplained Infertility |

UNEXPLAINED INFERTILITY

by John J. Stangel, MD

There are a variety of causes that can produce infertility, each with its own treatment and each with its own chance of success. But sometimes, the appropriate evaluation is completed, and no cause has been found. These couples we say have "unexplained infertility." "Infertility" is defined when a couple has been spontaneously attempting pregnancy for twelve cycles without success.  This is particularly frustrating to both doctor and couple because it does not answer the basic question, "What's wrong?" and gives no precise direction for specific treatment. There are treatments that are frequently used successfully such as stimulating ovulation or in vitro fertilization, but it would be better to try to learn specifically what is the problem and to try to address it.

Research on Pregnancy Loss may have come up with an answer!

Recently, we have had some hints at an answer to this problem and it has come from a surprising direction - the area of pregnancy loss. There are some couples who have no problem achieving a pregnancy, but who cannot carry to delivery. When this occurs three times in a row the couple is said to have "Recurrent Pregnancy Loss". Recent research suggests that some of these pregnancies were lost because the immune system of the mother attacked and rejected the pregnancy. Specific treatments have been developed to change this process and allow pregnancies to go forward to delivery. In fact, most of these treatments have been highly successful.

Suppose we were to treat "Infertility" as if we were treating recurrent miscarriage ? With the encouragement of the successes in treating recurrent miscarriage caused by the mother's Immune System - some of us in Reproductive Medicine began to wonder if this information could be helpful in other areas. Could it be that some couples with Unexplained Infertility did conceive - but the pregnancy was lost so early that there was never a positive pregnancy test? Could they be having very early miscarriages instead of infertility? ? Could it be that some couples with "Unexplained Infertility" are conceiving, but having very early miscarriages instead of infertility? Unfortunately there is no way to definitely know about very early pregnancy losses. We cannot rely on pregnancy tests because the loss is before the pregnancy hormone (HCG) is produced. Thus, the pregnancy test will be negative in spite of conception. However, we can test for some of the causes of pregnancy rejection and see if they are found more frequently among unexplained infertility couples than in other couples. This could support the idea that very early miscarriage was - in fact - the explanaton for some Unexplained Infertility. The research to try and prove this is currently still in progress.

How can our Immune System destroy a pregnancy?

It seems strange to believe that our body is able to reject something like a pregnancy - which is supposed to be there! Yet, such a thing has been demonstrated. This is what happens: The cause of the Rejection appears to be the body's natural immune system. This system has two components: the "humeral" or fluid part and the "cellular" part. The humeral component is composed of antibodies carried in the fluid part of the blood. In this category are Antiphosolipid antibodies, molecules capable of attacking cell membranes. In pregnancy these antibodies produce a blood clot at the place where the pregnancy is trying to attach to the uterine lining. The clot cuts off the blood supply which results in the death and loss of the pregnancy. In the cellular category is a group of white blood cells called "CD 56+ Natural Killer cells". These cells exist in everyone, male and female, pregnant or not. The frequency of these cells can be up to 16 %, and - at this level - are just a normal part of our defense against disease. However when the percent goes to 18% or more, the same cells turn on a pregnancy and appear to be capable of attacking placental tissue. The result is pregnancy loss! In theory if these two things occur very early in a pregnancy, there would not be time for a positive pregnancy test. As far as the patient could tell, she HAD NOT achieved a pregnancy at all!

Thus the Question arises: Suppose we were to treat the "Unexplained Infertility" patient as if she had an Immune problem?

We began testing Unexplained Infertility couples, and couples who have failed to become pregnant despite appropriate therapy - to see if there was any evidence of an immune problem. The early results confirmed a high incidence of positive findings. When we treated these couples as if they had an immune disorder - many achieved pregnancies! When we treated these couples for an immune disorder, many achieved pregnancies! However, I must emphasize that the number of patients we have treated thus far is too small to be statistically significant. That means that we cannot be certain in any one case - whether the pregnancy was really a result of our treatment or just a matter of luck. Couples do get pregnant, even infertility couples on occasion, without treatment. One must be very careful before definitely stating a cause and effect relationship between a new treatment and apparent success. Nevertheless, we are encouraged by our early data and hope to develop more information about the Immune Causes of "Unexplained Infertility" in the near future. © 2000 John Stangel, MD