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What is a Miscarriage?
Any unwanted, spontaneous pregnancy loss prior to the 20th week of pregnancy is considered a miscarriage. If such a spontaneous pregnancy loss occurs after the 20th week, it is referred to as a intrauterine demise.
Miscarriages are a relatively common occurrence, affecting nearly 15% of all pregnancies. However, repeat miscarriages (especially several miscarriages in a short period of time) may be caused by an underlying medical condition, which we will discuss in detail below. Women who experience repeated miscarriages should consult a miscarriage specialist to rule out, or receive proper treatment for, any such underlying causes of miscarriage.
Miscarriage Timing and Causes
The timing of a miscarriage can be very important in determining the underlying cause of the pregnancy loss. While more than 75% of all miscarriages happen in the first trimester, how far the pregnancy has advanced during this trimester can also provide further insight into the cause of the miscarriage.
|Very early pregnancy loss, characterized by a positive pregnancy test (hCG-level) that is not maintained. A chemical pregnancy never reaches the stage where a gestational sac is seen on ultrasound examination.||Loss of a clinical pregnancy, i.e., a pregnancy loss after the fetus has reached a stage that is visible on an ultrasound examination.|
Pregnancies that are confirmed by a blood test (hCG) are considered chemical pregnancies, because the gestation is confirmed only through chemical means, instead of ultrasound visualization. Clinical pregnancy is pregnancy that has reached a stage where the gestation can be seen on ultrasound examination. All “real” miscarriages are, indeed, losses of pregnancies that reached this “clinical” stage.
In life outside of fertility treatment settings, most chemical pregnancies are not recognized 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. Honest fertility programs do not consider chemical pregnancies as part of their IVF success rate statistics. Those statistics should exclusively include only clinical pregnancies.
The miscarriage of a clinical pregnancy can take place either before, or after, the ultrasound demonstrate a fetal heart rate. In a normally progressing pregnancy, a fetal heart should be demonstrable sometime between approximately 5.5 to 6 weeks from the first day of last menstrual period. If a pregnancy stops growing before that time, or if no heart is seen by the expected time (usually a sign of an abnormal pregnancy), then the pregnancy is generally considered to be a so-called 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 (for details, see below.)
Reasons for Miscarriage
Roughly 60% of all pregnancy losses is genetic in nature. 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 what patient population you are investigating. In general, the later the pregnancy loss occurs, the less likely is it genetic in nature.
|Genetic (chromosomal)||Caused by genetic abnormalities of the developing fetus. Represents up to 60% of all miscarriages. Risk is higher with advanced maternal age (see below).|
|Uterine abnormalities||Fibroid tumors or congenital uterine abnormalities such as septae. Often can be resolved with surgery.|
|Medical conditions||Diabetes mellitus, thrombophilia, thyroid disease, etc.|
|Immunological causes||Antiphopholipid 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 quite clearly associated with an increased miscarriage risk. So are certain congenital uterine abnormalities, especially so-called septae. If correctly diagnosed, these problems can usually, quite easily, be resolved through (often minor) surgery.
Medical conditions, such as diabetes mellitus, thrombophilias and thyroid disease, have also been associated with increased miscarriage risks. In conjunction with diabetes, it has been demonstrated that this 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 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 for miscarriages, discussed below. Thrombophilias (i.e., medical conditions that predisposes to an increased risk of blood clotting) have in recent years also been associated with an increased risk to miscarry. 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 so-called Reproductive Autoimmune Failure Syndrome (RAFS), characterized by the presence of autoimmune abnormalities.
Immunological causes of miscarriages have remained the most controversial issues relating to pregnancy loss. As explained below, CHR believes that immunological causes should be suspected when i) relevant medical history (self or in family members) or ii) repeated pregnancy losses exist. The scientific community is greatly divided on these subjects, with zealots on both sides of the issues unfortunately often taking extreme, and unsupportable, positions. We believe that our understanding of immunological causes of pregnancy loss, here at CHR, is well supported by the literature, and, indeed, is reflective of a more centrist position on the various issues. Moreover, our position is, to a great degree, also based on research, performed by our own investigators through our own investigations, and we, therefore, can fully stand behind the results obtained in these investigations.<
Video: Autoimmunity and Miscarriages
Dr. Norbert Gleicher explains how CHR can help women prevent miscarriages.
Repeat Miscarriages and Immunological Issues
Since miscarriages occur relatively frequently, and since immunological causes are in a general population relatively rare, the suspicion of immunological pregnancy loss has to be awakened in physicians when either of the two conditions exists: i) a relevant medical history (either personal, or familial) or ii) repeated pregnancy loss (habitual pregnancy loss). This is yet another important terminology, describing the female who either experienced three consecutive first-trimester losses or two, with one in the second trimester.
We noted earlier that the later pregnancy loss occurs (i.e., before or after fetal heart), the less likely is the pregnancy loss genetic in nature, 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 (except for 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, among others. 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.
Age and Miscarriage
If one looks at unselected populations of women, the average miscarriage rate is not that high. Roughly 15% of all pregnancies are lost at various possible miscarriage stages. This number can be misleading, however, especially for patients with fertility problems who, very often, have a much higher miscarriage risk. Their 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 further ages, that risk even further increases.
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 CHR publications, CHR 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 reduction in chromosomal abnormalities.
How to Prevent Miscarriages
CHR Publications on Autoimmunity
- Journal of Autoimmunity Reviewing the last 10 years of medical literature, the study found considerable data suggesting significant negative impact of autoimmunity on female reproductive success. Combining this finding with CHR's recent work on the FMR1 gene, the article points out the possibility that the FMR1 gene stands at the crossroad of ovarian reserve and autoimmunity.
Gestational dermatosis shortly after implantation associated with parental class II HLA compatibility and maternal immune activation: preliminary report of a prospective case series.Dermatology The case series reports on 7 couples who presented with typical skin rash occurring days after embryo implantation. All female partners reported clinically significant allergies and autoimmune findings, and all but one couple demonstrated class II HLA compatibility. The study speculates that the "implantation rash" may be a maternal immune response to embryo implantation in women with prior immune activation associated with class II HLA compatibility.
One of the reasons why immunological pregnancy loss has remained such a controversial and divisive subject is that investigators have not been able to reach consensus about how to treat affected patients. Some authorities, therefore, argue that, since we have no proven treatment, why even bother with diagnosing these patients?
Indeed, it is correct that in certain situations we do not have a proven treatment. We noted above already that there is, for example, no established treatment to normalize the increased miscarriage risk with autoimmune thyroid disease. Some authorities have suggested that treatment with intravenous gamma globulin was effective in this situation; however, a majority of studies were unable to confirm this. In other clinical situations, for example in the presence of APA/RAFS, many studies, including some from CHR, have demonstrated that a variety of treatment approaches may be quite effective. These include aspirin, corticosteroids, heparin and, on occasion, intravenous gamma globulin.
As we noted above, we perceive CHR's treatment philosophy in this area as centrist. While some colleagues on one extreme propagate the aggressive use of high dosage medications, including gamma globulin in practically all patients, and colleagues on the other extreme reject all treatments, we, based on our own data, and 20 years of experience with thousands of affected patients, have come to strongly believe in the individualization of patient care, based on the very specific immune conditions present in patients at any given time.
Physicians who really understand abnormal autoimmune function know that autoimmune function is never static. Patients with abnormal autoimmune function, whether they have overt clinical disease, or suffer from only sub-clinical autoimmunity, go through periods of exacerbations and remissions. Therefore, to treat every patient in the same way, at all times, does not make sense! Treatment at CHR is, therefore, adjusted to the actual immune status of the patient, as she goes through pregnancy. As a consequence, over 99% of our patients are off most medications by the time they reach approximately 20-23 weeks gestation. And because they do not have to take medications for the remainder of the pregnancy, the known, and frequent, complications from these medications are only very rarely seen.
Why CHR for Miscarriage Prevention?
As one of the nation's leading fertility centers, we have an unprecedented level of experience with female fertility and preventing miscarriages.
Our physicians at the CHR are world-renowned experts in miscarriage prevention and have conducted extensive amounts of research on the diagnosis and treatment of autoimmunity-related miscarriages. We thoroughly review each patients' history and test results to ensure that any possible underlying cause of miscarriage is properly identified and treated.
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Written by Norbert Gleicher, MD
Last Updated: December 31, 2013