Introduction

Pregnancy loss, more commonly referred to as "miscarriage", is the most common complication of pregnancy. Approximately 10-15% of all first-time pregnancies result in miscarriage. In most instances, you can expect a similar miscarriage rate in subsequent pregnancies. Recurrent pregnancy loss is commonly defined as 3 or more miscarriages. Approximately 5% of couples attempting pregnancy have recurrent pregnancy loss. In the past, few couples were diagnosed with a specific cause for miscarriage. Recently, progress has been made in understanding recurrent pregnancy loss that was previously unexplained.

Diagnosis

The most important part of treating couples with recurrent pregnancy loss is determining the cause or diagnosis. Causes of recurrent miscarriage include chromosomal defects, uterine defects, hormone deficiencies, and immunological factors. At Rotunda, we conduct a thorough evaluation of each couple to determine the cause of miscarriage. After diagnosis has determined a cause, the correct treatment plan can be discussed and decided upon.

Chromosomal Abnormalities

Chromosomal abnormalities can be caused by abnormalities that exist in the genetic structure of one or both parents. These abnormalities are not life threatening to the parents, but when passed to the embryo, they can cause miscarriage. Chromosomal analysis of both partners can be done to determine if abnormalities exist by actually looking at the chromosomes of blood cells from both partners. Other abnormalities can result during conception and will only exist in the growing embryo. If miscarriage occurs, the cells from the embryo can be tested to determine the existence of abnormalities.

Most usually, chromosomal abnormalities are not treatable. Genetic counseling can offer guidance to couples on the chances of passing abnormalities to their children. Couples can then make informed decisions about continuing to try to conceive using their own eggs and sperm, trying donor eggs or sperm, looking further into adoption, or remaining childless.

Uterine Defects

Defects of the uterus can be caused by several factors. Some women are born with defects in the structure of the uterus caused by genetics or exposure in utero to certain chemicals. The most well known defect caused by a chemical is that of DES. DES is an estrogen like compound used from the 40's through the 70's to treat complications of pregnancy. Children born with this treatment experienced fetal anomalies, including defects in the uterus.

Other defects can be caused by polyps (small growths in the uterine lining) or fibroids, which can cause problems with implantation of the embryo or retard the growth of the fetus, eventually leading to miscarriage.

Uterine defects can be diagnosed using hysterosalpingography, a procedure in which dye is injected into the uterus and then photographed using an X-ray (see Testing and Diagnosis). Treatment may include surgery to go in and reshape the uterus or remove polyps or fibroids.

Hormone Deficiencies

This is an uncommon deficiency associated with very early abortion. The cause is an inadequate corpus luteum (yellow body) functioning on the ovary at the place of ovulation (the old follicle), which is the gland that produces progesterone during early pregnancy. Progesterone is the hormone that is necessary to maintain the pregnancy. If this hormone is not present in sufficient quantities, the pregnancy will abort, sometimes even before it is detected.

Women experiencing a luteal phase defect often have this problem. Luteal phase defects are also caused by a lack of progesterone produced by the corpus luteum during the cycle. Luteal phase defects can be detected by endometrial biopsies and serum progesterone levels during the luteal phase.

This type of hormone deficiency can be treated with supplemental progesterone given during the luteal phase or the first trimester of pregnancy when an inadequate corpus luteum is suspected. Supplemental progesterone is also given during superovulation cycles such as IVF or GIFT to counteract the increased levels of estrogen produced by multiple follicles. Progesterone supplementation is often maintained through the first trimester of these pregnancies to ensure adequate levels.

We have also seen situations where endometrial thickness is poor, although the composition is normal. Optimal endometrial thickness is 8-13mm at the time of the LH surge. We have come to suspect that certain patients may be deficient in estrogen or response to estrogen. This estrogen is required to build up the lining in the first half of the cycle. Thin endometrial linings have been associated with recurrent miscarriage and estrogen inadequacy may be the cause. This may be treated with superovulation with or without supplementation with Viagra.

Immunologic Factors

This is one of the newest and sometimes most controversial problems associated with recurrent pregnancy loss. Autoimmune problems where the body produces antibodies against other body proteins has been linked to miscarriage. These problems are diagnosed by tests such as Anti-Nuclear Antibodies (ANA) and Anti-Phospholipid Antibodies (APA), which detect the presence of these antibodies in the woman's blood. These antibodies may cause an abnormal clotting event to occur during pregnancy, which causes interruption of the blood flow to the placenta. As this interruption becomes more and more severe, the fetus begins to starve for oxygen and nutrients and eventually dies. This eventually leads to miscarriage.

Other problems with blood coagulation have recently come to light as being associated with both infertility and recurrent miscarriage. These all have the same basic outcome by clotting off the placenta and causing miscarriage at various stages in the pregnancy.

The most notable treatment for immunologic factors of miscarriage is the administration of low dose aspirin, heparin, and steroids. These reagents cause a masking effect that can help prevent clotting off the placenta. While the benefits from this treatment remain controversial in the medical community, our experience with patients has led us to believe that many patients receive a benefit from this treatment. This benefit has been realized in a dramatic increase in the number of pregnancies achieved and delivered after we initiated a more general use of this treatment.

In a large group of patients, who were previously diagnosed as unexplained infertile or unexplained miscarriage, our work with hematologists has shown an association between pregnancy loss, infertility, and certain coagulation disorders. Empirical treatment for the diagnosis of these coagulation disorders by the use of aspirin and heparin has been offered to our patients. While patient caution is indicated, we feel there are great benefits associated with this treatment.