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Immunology may be key to pregnancy loss (updated) by Carolyn Coulam and Nancy Hemenway

Last Updated: July 15, 2005
Page: 1

Until the last decade, there was little a couple could do if they suffered from recurrent pregnancy losses. Miscarriages that couldn't be attributed to chromosomal defects, hormonal problems or abnormalities of the uterus were labeled "unexplained," and couples would continue to get pregnant, only to suffer time and again as they lost their babies. New research, however, has provided information on the causes of the heretofore unexplained pregnancy losses allowing more effective treatment enabling women to carry their babies to term.

About 15 to 20 percent of all pregnancies result in miscarriage, and the risk of pregnancy loss increases with each successive pregnancy loss. For example, in a first pregnancy the risk of miscarriage is 11 to 13 percent. In a pregnancy immediately following that loss, the risk of miscarriage is 13 to 17 percent. But the risk to a third pregnancy after two successive losses nearly triples to 38 percent.

Many doctors do not begin testing for the cause of pregnancy loss until after three successive miscarriages. However, because the risk of loss to a third pregnancy after two successive miscarriages is so high, the American College of Obstetrics and Gynecologists (ACOG) now recommends testing after a second loss-especially for women over the age of 35.

There are two major reasons for recurrent spontaneous abortion (RSA), or miscarriage. One is that there is something wrong with the pregnancy itself, such as a chromosomal abnormality that curtails embryonic development. (A fertilized ovum is an embryo until 10 weeks gestation, and a fetus thereafter. Most miscarriages, though not all, occur between six and eight weeks, with expulsion taking place four weeks later, between 10 and 12 weeks.)


The best way to find out if the pregnancy itself is the problem is to test the chromosomes of the aborted embryo. While in many cases this information is not available, requesting genetic testing after a dilation and curettage (D&C) for a missed abortion can often give couples some definitive answers about what went wrong. An alternative to obtaining genetic testing of the pregnancy is to test the chromosomes of the couple. This test is called a karyotype and involves a blood test for each partner so that both sets of chromosomes can be evaluated for abnormalities which may cause RSA, or which may be passed on to children. In addition to chromosomal problems, the pregnancies can have either abnormal genes or abnormal DNA contributing to their losses.  Gene abnormalities associated with recurrent pregnancy loss include mutations in HLAG genes contributed by either the father or the mother as well as gene deletions on the Y chromosome contributed by the father.  Fragmented DNA from the sperm has also been associated with early pregnancy loss.

The other major category of causes of RSA is a problem within the uterine environment that does not allow the pregnancy to grow properly. The most frequent environmental causes of pregnancy loss are attributable to immunologic factors followed by thrombophilic or blood clotting factors.  Other possible environmental causes of pregnancy loss are hormonal (not enough of necessary hormones to sustain the pregnancy) and anatomic (such as structural abnormalities of the uterus).

Anatomic problems may be detected with a hysterosalpinogram, hysteroscopy or hysterosonogram. Assessment of the hormonal environment looks at hormone levels and uterine response at the expected time of ovulation and implantation, usually through an endometrial biopsy or high level ultrasound examination.

The final way to determine an environmental cause of multiple miscarriages is through immunologic and thrombophilic testing.   To better understand the rationale for immunologic and thrombophilic testing, the roles of the immune and blood clotting systems in nature and reproduction will be reviewed.

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