What Are Repeated Miscarriages?
Any unwanted, spontaneous pregnancy loss prior to the 20th week of pregnancy is considered a miscarriage. Miscarriages are a relatively common occurrence, affecting nearly 15% of all pregnancies. However, repeat miscarriages, defined by either three consecutive first-trimester losses or two with one in the first trimester and one in the second trimester, suggests that there may be an underlying medical condition. Women experiencing repeat miscarriages should consult a recurrent miscarriage specialist to avoid further losses.
Roughly 60% of all pregnancy losses are genetic in nature–in these cases, genetic abnormalities of the fetus causes the miscarriage. This leaves about 40% for other miscarriage causes, but exact statistics are hard to come by. The prevalence of the various other causes of pregnancy loss also depends greatly on the patient population being investigated. In general, the later the pregnancy loss occurs, the less likely that it is genetic in nature.
Common Causes of Miscarriages:
Genetic (chromosomal) Caused by genetic abnormalities of the developing fetus. Represents up to 60% of all miscarriages. The risk is higher with advanced maternal age.
Fibroid tumors or congenital uterine abnormalities such as septae, these can often be resolved with surgery.
Diabetes mellitus, thrombophilia, thyroid disease, etc.
Antiphospholipid Antibody Syndrome (APA), Reproductive Autoimmune Failure Syndrome (RAFS).
Roughly 60% of all pregnancy losses are genetic in nature. These genetic abnormalities can be due to conditions passed on from the parents or simply due to parental age. Miscarriage risks increase with advancing female age, and once a woman reaches age 42, her miscarriage risk can be as high as 50%.
Uterine abnormalities, especially fibroid tumors, if badly located, have been clearly associated with an increased miscarriage risk. So are certain congenital uterine abnormalities, especially so-called septae. If correctly diagnosed with HSG or HSN, these problems can usually, quite easily, be resolved through (often minor) surgery.
Medical conditions, such as diabetes mellitus, thrombophilia, and thyroid disease, have also been associated with increased miscarriage risks. With diabetes, the risk can be normalized if the patient’s blood sugar levels are well controlled. The risk with thyroid disease is more difficult to define and address since it does not correlate with thyroid function (which can be quite easily adjusted with medications in most women) but with underlying autoimmune abnormalities for which we really have no good therapeutic remedies. In this sense, thyroid disease should be probably best understood to be one of the immunological causes of miscarriages, discussed below. Thrombophilia (i.e., medical conditions that predisposes individuals to an increased risk of blood clotting) have in recent years also been associated with an increased risk of pregnancy loss. These, however, also overlap with immunological causes of pregnancy loss since one of the most prevalent thrombophilias is the so-called Antiphospholipid Antibody Syndrome (APA), or as we have come to call it in reproductive medicine, the Reproductive Autoimmune Failure Syndrome (RAFS), characterized by the presence of autoimmune abnormalities.
Since miscarriages occur relatively frequently and immunological causes are relatively rare in a general population, we suspect immunological pregnancy loss when either of the two conditions exists: 1) a relevant medical history (either personal, or familial) or 2) repeated pregnancy loss, or a habitual pregnancy loss, defined by three consecutive first-trimester losses or two, with one in the second trimester.
Causes of Miscarriage and Timing:
Pregnancies that are confirmed only by a blood test (hCG) are considered chemical pregnancies, because the gestation is confirmed through chemical means, instead of ultrasound visualization. Clinical pregnancy is the pregnancy that has reached a stage where the gestation can be seen on ultrasound. Miscarriages refer to losses of pregnancies that reached this “clinical” stage, past the chemical stage.
In life outside of fertility treatment settings, most women do not know they had chemical pregnancies since most women do not have pregnancy test so early in their pregnancy. During infertility treatments, however, we do diagnose these very early pregnancy losses routinely, because every treatment cycle is followed up with a very early pregnancy test.
The miscarriage of a clinical pregnancy can take place either before or after the ultrasound showed a fetal heart rate. In a normally progressing pregnancy, a fetal heart should be present sometime between approximately 5.5 and 6 weeks from the first day of last menstrual period. If a pregnancy stops growing before the fetal heart, or if no heart is seen by the expected time (which is usually a sign of an abnormal pregnancy), then the pregnancy is generally considered to be a “blighted ovum” or missed abortion. Whether a pregnancy loss occurs before or after fetal heart activity is quite important, because the timing of the miscarriage can provide a hint at the underlying cause.
We discussed earlier that the later pregnancy loss occurs (i.e., before or after fetal heart), the less likely is the pregnancy loss due to fetal genetic issues and the more likely is it medically induced, with much of the medically induced pregnancy loss being immunological in nature. The same also applies to a diagnosis of multiple losses: The more miscarriages a woman has experienced, the more likely are her losses medical in nature and the less likely are they of genetic/chromosomal origin. (An exception to this rule is a genetic condition called a translocation, which also can cause multiple, repeated miscarriages).
A history of habitual miscarriages should always raise the suspicion of immunological pregnancy loss. Such a suspicion should also arise if the patient or close family members report a history of autoimmune diseases or relevant symptomatology, like joint pains, unexplained rashes, etc.
Immunological causes of miscarriages have remained the most controversial issues relating to pregnancy loss. The scientific community is greatly divided into these subjects, with zealots on both sides of the issues unfortunately often taking extreme, and unsupportable, positions. However, we believe that our understanding of immunological causes of pregnancy loss is well supported by the literature and is reflective of a more centrist position. Moreover, our position is largely based on research performed by our own investigators, which means we can fully stand behind the results obtained in these investigations.
Age and Miscarriage:
If one looks at an unselected population of women, the average miscarriage rate is not that high. Roughly 15% of all pregnancies are lost at various possible stages. This number can be misleading, however, especially for patients with fertility problems who, very often, have a much higher risk. Their miscarriage risk can be higher for a variety of reasons: For example, women with fertility problems are usually older than the average population that conceives. And miscarriage risks increase with advancing female age. Indeed, once a woman reaches the age of 42 years, her risk of miscarriage reaches approximately 50%. As she gets older, that risk rises even further.
The principal reason for this increasing miscarriage rate with advancing age lies in the fact that more than half of all miscarriages are due to genetic (i.e., chromosomal) abnormalities in the embryo. And such chromosomal abnormalities increase with advancing maternal age.
An interesting development has been taking place in this regard: As detailed in a few recent publications, some physicians have discovered that dehydroepiandrosterone (DHEA) supplementation in women with diminished ovarian reserve (who usually have higher miscarriage risks than those with normal ovarian function) significantly reduces their miscarriage risks through a reduction in chromosomal abnormalities.