Pregnancy Loss and Miscarriage
Human reproduction is not very efficient. No more than 1/3 of the eggs a woman makes is capable of a successful pregnancy. Often, eggs do not fertilize, or do not produce a diagnosed pregnancy. When an abnormal egg does produce a recognized pregnancy, the pregnancy is usually lost as a miscarriage. Sadly, miscarriages are fairly common. They are certainly devastating for the couple trying to have children.
Because pregnancy losses are anything but rare, it is not really helpful to spend a lot of money and energy to evaluate each one. It is appropriate to evaluate a couple who has repeated pregnancy losses. The medical term for miscarriage is spontaneous abortion. Unfortunately, the word abortion has bad connotation in our society, but the medical terminology is still used in professional circles. Therefore repeated pregnancy loss is called recurrent abortion. The insurance companies want to use the term habitual abortion. That does not and should not imply that the patient or anyone else deliberately disrupted a pregnancy.
At what point do we start the detailed evaluation, and what is the testing? Typically, recurrent abortion is defined as 3 or more miscarriages. A purist does not initiate an evaluation until a couple has experienced at least 3 losses. I think a woman over the age of 35 may deserve evaluation after 2 miscarriages, especially if she has trouble becoming pregnant, too. After the age of 35, her pregnancy potential begins to decline, and her risk of miscarriage or having a child with the wrong number of chromosomes increases.
Not all causes of miscarriage can be accurately identified. We can diagnose and treat many of them. One of the more common known causes of pregnancy loss is abnormal formation of the uterus. Although not all uterine malformations increase the risk of miscarriage, one form increases the risk to as high as 70% to 90%, depending on the severity of the anomaly. Even so, the other abnormalities are associated with an approximately 25% risk of other obstetrical problems. Uterine anomalies are actually easy to diagnose. I use am ore classic technique of X-ray study called a hysterosalpingogram or HSG, for short. The study involves injecting an X-ray contrast material through the cervix, into the uterine cavity, while performing fluoroscopic visualization of the pelvis. The contrast material outlines the uterine cavity, and should flow through the fallopian tubes into the pelvic cavity. If performed properly, this study provides excellent information about the anatomy of the uterine cavity and fallopian tubes.
An alternative technique is to inject saline into the uterus, using ultrasound to obtain images of the uterus. The advantage is that there is no use of X-ray, even though X-ray is minimal using today’s equipment. The disadvantage is that performing sonohysterography; it is not possible to obtain information about the fallopian tubes. Either technique will assist in identification of a uterine anomaly.
The uterine anomaly which increases the risk of miscarriage is a uterine septum. A septum, or wall, in the uterine cavity is the result of incomplete fusion of the 2 tubular structures, Mullerian ducts, which form the uterus in the developing fetus. The septum has almost no blood supply. As a result, a pregnancy has very little chance of surviving if its placenta implants on a septum. Depending on the size of the septum the risk of miscarriage is as high as 90%.
A uterine septum is easy to repair. It does require outpatient surgery. First, it is necessary to determine the abnormal formation is really a uterine septum, and not a uterus which has 2 uterine horns. A septate uterus has a single body with a divided cavity. A bicornuate uterus has 2 uterine bodies attached to a single cervix. The bicornuate uterus is an example of a greater degree of failed fusion of the Mullerian ducts, but is not associated with an increased risk of miscarriage. It is probably not advisable to repair most such anomalies. The risks usually are greater than the rewards. I will discuss that in a following paragraph. Let’s focus on the septum, for right now.
First, we confirm the diagnosis. The most reliable way to do that is by using a laparoscope. A laparoscope is a telescope-like device inserted through the navel of an anesthetized patient. With a laparoscope we can usually obtain excellent visualization of the uterus, ovaries and fallopian tubes. If the uterus has a single body, and a divided cavity, we insert another, smaller telescope, a hysteroscope, through the cervix into the uterine cavity. Under direct visualization, it is possible to remove the septum. There are several techniques. Some use electro-cautery. There are tiny scissors which can be inserted through operating channel of the hysteroscope. I prefer to use one of the surgical lasers available. It causes less collateral tissue injury than cautery, and there is less bleeding than using scissors. I place a small balloon catheter in the uterus after repairing a septum. I am concerned that the operative surfaces where the septum was removed may stick together and recreate the original problem. I remove the catheter at the post operative visit a week after surgery.
What do we do with a bicornuate uterus? Usually nothing. A bicornuate uterus does not increase the risk of miscarriage. It does increase the risk of somewhat premature labor and increases the risk of an abnormal presentation of the fetus when a woman goes into labor. The abnormal presentation, or transverse lie, requires Caesarian section, because the baby will not come out side-ways. Repair of a bicornuate uterus creates an even greater risk to both a pregnancy, and the mother. The repair involves opening the uterus transversely, and then sewing it up to unify the cavity and uterine bodies into a single structure. The result is a big scar across the top of the unified uterus. A scar of this type in the muscular portion of the uterus is very weak. There is a significant risk that the scar will rupture during pregnancy, and certainly during labor, putting both mother and child in jeopardy.
There is a significant public awareness of auto-immune problems as a cause of miscarriage. Indeed, on some occasions, a woman does make antibodies that increase the potential for pregnancy loss. Most commonly the OB-GYN tests for things like Lupus or tests for something called anti-nuclear antibody (ANA). These tests are not very helpful, but at one time were all we had. My preference is to have a battery of tests performed to look for antibodies to cell surface proteins which have been shown to increase the risk of recurrent pregnancy loss. The laboratory I use is operated by Dr. William Kutteh at the University of Tennessee in Memphis. He tests for a whole panel of antibodies whose names will twist your tongue and confound our editor. If you really want to know there names, I will gladly provide them if you wish to e-mail me. Needless to say, these tests are not run in most clinical laboratories, and are rather arcane.
What is the treatment for the antibody problem? Actually, it is fairly simple. Some physicians use aspirin. Others, like I do, use low dose Heparin. Some use both. Heparin is an anticoagulant, and the initial think was that it should be used to prevent blood from clotting in the early placenta. Actually the beneficial effect of Heparin in this case is its anti-inflammatory action. Aspirin is also an anti-inflammatory agent in addition to slowing the clotting mechanism. Another word about Heparin is in order. Heparin is available in 2 different forms. The older version is referred to as un-fractionated. It is really just fine for most people. Unfortunately, a tiny number of people have a bad reaction to un-fractionated Heparin, and loose all of their platelets – the particles in blood which are necessary participants in normal blood clotting. Someone who looses platelets as a result of using un-fractionate Heparin is not going to survive. Fortunately the problem is quite rare, but I still do not use un-fractionated Heparin. I prescribe low molecular weight Heparin, which is not associated with destruction of platelets. It is best to continue Heparin and/or aspirin treatment for the duration of the pregnancy, if it is appropriate to initiate the protocol, in the first place.
If a pregnancy has the wrong number of chromosomes, it will not produce a normal child. In fact, the pregnancy will probably be lost. About 0.2% of normal people have the correct number of chromosomes, but a piece of one is broken off and stuck to another one. This condition is called a balanced translocation. When someone with a balanced translocation makes eggs or sperm, two thirds of the pregnancies they produce will not have the correct chromosomal make up. As a result, in about 5% of couples with repetitive miscarriages, one member of the couple has a balanced translocation. Treatment options are limited. Today, we do have a bit more to offer than we did 15 years ago. Previously, if the man had a balanced translocation, the only treatment option to avoid repeated losses was to use donor sperm. There was no help if his wife had a balanced translocation. We can do more, today. In addition to donor sperm, we can use an egg donor, if the chromosome problem is the wife’s. If the couple does not wish to use donor sperm or eggs, we can biopsy embryos, in some cases, to determine which embryos have the correct chromosome complement. Unfortunately, the process is expensive, and we may not have a normal embryo to place in the uterus.
In the recent past, some professionals were proposing that something called “blocking factor” in the woman protected a pregnancy from the foreign material called a pregnancy. After all, a pregnancy is much like an organ transplant in that it is not genetically the same as the mother. The hypothesis was that the mother was supposed to make something that confused her immune system into not recognizing the pregnancy as foreign. Supposedly, if a husband and wife had immune systems which would allow them to donate organs to each other, she failed to make “blocking factor”. As a result, her body treated her pregnancy like a foreign organ transplant, and “rejected” the pregnancy. The treatment advocated for lack of blocking factor was to irradiate white blood cells of the husband and inject them into the wife. Supposedly, this inoculation with dead white blood cells of the husband would induce the production of “blocking factor” by the wife. Many clinicians were skeptical. No one was ever able to find “blocking factor”. When a properly designed research project was initiated, an over sight committee cancelled the investigation before the proposed number of couples was treated. It was very clear that all the treatment with white blood cells did was delay pregnancy loss until second trimester. The later miscarriage was associated with more surgery, more blood loss and more transfusions. No one advocated treatment for “blocking factor”, anymore.
Today, we have another controversial treatment for pregnancy loss, and at least one group advocates this treatment to try to improve IVF pregnancy rates. Again, the basis for the recommendation looks to the immune system for answers and treatment of problems. Again, the hypothesis is that the woman is making antibodies to her pregnancy. The proposed treatment is intravenous infusion of immune globulins (IVIG). A few investigators claim benefit, but their findings cannot be duplicated by others. For that reason, most Reproductive Endocrinologists are still skeptical. It is an expensive process, and insurance does not cover this treatment. It is listed as experimental. Besides, infusing IVIG is not entirely harmless. To produce a single treatment requires blood from 750 blood donors. Yes, our blood supply is fairly safe, but without proven benefit, I hesitate to incur the risk of 750 transfusions. Many of us remember the folly of “blocking factor”.
Even though most miscarriages are still unexplained, we can identify the cause of many, and provide beneficial treatments. In all probability, the miscarriages that do not have a demonstrated cause are gene abnormalities. As we noted in a previous chapter, there is the occasional “typo” in transcribing the genetic code. As a rule, such random events are not repeated. The overwhelming majority of couples who have suffered a miscarriage have perfectly normal subsequent pregnancies.
