WHAT IS A MISCARRIAGE?
Any unwanted, spontaneous pregnancy loss until the second trimester of pregnancy is considered a miscarriage. Once such a spontaneous pregnancy loss occurs after approximately 23-24 weeks of gestation, it is considered a so-called intrauterine demise.
Miscarriages can take various forms. They then have various names attached to them. Here is an explanation of terminologies:
A chemical pregnancy is a very early pregnancy loss, characterized by a positive pregnancy test (hCG-level) which, however, is not maintained. Moreover such a pregnancy never reaches the stage where a gestational sac is seen on ultrasound examination. Therefore, the name “chemical” pregnancy, since the gestation is diagnosed only by chemical means.
In contrast, a so-called clinical pregnancy is characterized by the fact that it has reached a stage where the gestation can be seen on ultrasound examination. All “real” miscarriages are, indeed, losses of pregnancies, which, at some point, did reach this “clinical” stage. In routine life, most chemical pregnancies are not recognized since most women do not have very early pregnancy tests performed. During infertility treatments we, however, do diagnose these very early pregnancy losses quite universally because every treatment cycle is followed by a very early pregnancy test. Honest fertility programs do, however, not consider chemical pregnancies as part of their pregnancy success statistics. Those statistics should exclusively include only clinical pregnancies.
The miscarriage of a clinical pregnancy can take place either before, or after, the pregnancy was demonstrated (usually by ultrasound) to show a fetal heart rate. In a normally progressing pregnancy, a fetal heart should be demonstrable sometimes between approximately 5.5 to 6 weeks from 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 since the timing of pregnancy loss can provide a hint at the underlying cause (fur further details see below).
WHY ARE THERE SO MANY MISCARRIAGES?
If one looks at unselected populations of women, the average miscarriage rate is actually not that high. Roughly 15% of all pregnancies are lost at various possible miscarriage stages. This number can, however, be misleading, 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,as we will be discussing in more detail below. 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 principle reason for this increasing miscarriage rate with advancing age, lies in the fact that approximately 85% of all miscarriages, that occur, are due to genetic (i.e., chromosomal) abnormalities. And such chromosomal abnormalities increase with advancing female age.
WHAT ARE THE PRINCIPAL CAUSES OF MISCARRIAGES?
We already mentioned that roughly 85% of all pregnancy loss is genetic in nature. This leaves only approximately 15% for other explanations and causes. Amongst those other causes, exact statistics are difficult to come by. Moreover, the prevalence of the various other causes for pregnancy loss will, of course, greatly depend on what patient population you are investigating.
In principle, most of the remaining miscarriages are caused by uterine, general – medical or immunological causes. Some investigators believe that low luteal progesterone levels can also be a cause of pregnancy loss; we, however, do not believe that the literature really supports such an assumption.
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 is has been demonstrated, however, 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 to 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 bee probably best understood to be one of the immunological causes for miscarriages, discussed below. Thrombophilias (i.e., medical conditions, predisposing 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, quite clearly, remained the most controversial issues relating to pregnancy loss. 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.
CHR has been one of the leaders in the field of reproductive immunology. We have conducted some of the most basic research in the field of immunological pregnancy loss.
Since miscarriages occur relatively frequently, and since immunological causes are in an unselected patient population relatively rare, the suspicion of immunological pregnancy loss has usually to be awakened in physicians by either a relevant medical history (either personal, or familial) or by repeated (or 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, therefore, always, amongst others, 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..
HOW TO TREAT IMMUNOLOGICAL PREGNANCY LOSS?
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 on how to treat affected patients. Some authorities, therefore, argue that, since we have no proven treatment, why even bother with diagnosing these patients?
It, indeed, is correct that, in certain situations, we do not have proven treatments. 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 of 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. To treat every patient,therefore, in the same way, at all times, in our opinion, 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?
As one of the nation’s leading fertility centers,
we have an unprecedented level of experience with women who miscarry.
If you wish to receive an unbiased opinion about a miscarriage situation please contact us.
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