Miscarriage and Its Associations

Stephen Brown, M.D.


Semin Reprod Med. 2008;26(5):391-400. 

In This Article

Abstract and Introduction


Despite many years of study, abnormal chromosome number remains the most common and well-documented cause of miscarriage. Nonchromosomal factors that have been associated with miscarriage are many and include endocrine abnormalities, anatomic abnormalities, inherited and acquired thrombophilia, environmental exposures, immunologic factors, and others. This article attempts to provide a brief overview and critique of the frequently reported factors. In addition, we call attention to the fact that, to be most helpful, modern studies of miscarriage need to provide details about the sonographically determined gestational age and fetal anatomic development prior to or at the time of pregnancy loss. Such information will be critical in helping to sort out which miscarriage-associated factors are more relevant at which stage of fetal development.


Human reproduction is remarkably inefficient in the sense that a large proportion of conceived pregnancies are not ultimately successful. Our understanding of why this is so is, in general, limited, and the list of possible causes of pregnancy loss is extremely long. The purpose of this article is to provide an overview of the scope of miscarriage and many of the clinical circumstances in which it arises.

In its broadest definition, miscarriage refers to any fetal loss from conception until the time of fetal viability at ∼23 weeks gestation. Although miscarriage is commonly said to occur in ∼15% of pregnancies, total reproductive losses are much higher if one considers losses that occur prior to clinical recognition. As is illustrated in Figure 1, the majority of clinically recognized miscarriages occur during the first trimester. This is important to bear in mind because the etiology of miscarriage varies greatly according to gestational age, with preimplantation losses, pre-fetal losses, and losses where there are only rudimentary fetal remains being more likely to be due to intrinsic fetal problems (e.g., chromosome abnormality), whereas later losses are more likely to be due to extrinsic or maternal factors. Unfortunately, most literature lumps miscarriages into fairly broad categories, with "early" meaning less than 24 weeks in some cases and less than 19 or 13 weeks in others, making it impossible to sort out which associations are strongest with which gestational age.

Figure 1.

Diagram showing the approximate proportions of pregnancy outcomes. The majority of pregnancies end before clinical recognition. Of pregnancies that do reach clinical recognition, the vast majority of losses occur prior to the end of the first trimester.

Further compounding this issue is the fact that there is no consensus about how miscarriage should be dated in the modern world. Classically, miscarriage was evidenced by bleeding and passing of tissue, and gestational age was determined by last menstrual period (LMP) or perhaps by the size of the fetus if one was present. Now we have sensitive urine pregnancy tests that allow us to detect many failed pregnancies that, in the past, would have not been documented. Patients frequently report "miscarriages" that would never have been documented in an earlier era. Do such miscarriages have the same implications as those in classic studies? In addition, we have early sonography that provides a wealth of information about gestational age and the presence (or absence) of embryonic development. Ideally, studies of miscarriage should now provide details about whether or not a viable fetus was ever present and about how the gestational ages of miscarriages are determined. Few studies do provide this kind of detailed information.


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