In treating recurrent pregnancy loss, evidence supports repairing anatomic abnormalities, correcting preexisting endocrine disorders, and treating APS and other thrombophilic disorders.
Advances in the ability to document and diagnose early pregnancy reveal that spontaneous pregnancy loss is a common event. Spontaneous pregnancy loss is, in fact, the most common complication of pregnancy. Approximately 70% of human conceptions fail to achieve viability, and an estimated 50% are lost before the first missed menstrual period (1). Most of these pregnancy losses are unrecognized. Studies using sensitive assays for human chorionic gonadotropin (hCG) indicate that the actual rate of pregnancy loss after implantation is 31% (2). Loss occurs in 15% of pregnancies that are clinically recognized before 20 weeks of gestation from last menstrual period (3,4).
Traditionally, recurrent abortion has been defined as the occurrence of three or more clinically recognized pregnancy losses before 20 weeks from the last menstrual period. Using this definition, recurrent pregnancy loss occurs in approximately 1 in 300 pregnancies (2). Clinical investigation of pregnancy loss, however, may be initiated after two consecutive spontaneous abortions, especially when fetal heart activity is identified before any of the pregnancy losses, when the women is older than 35 years of age, or when the couple has had difficulty conceiving (5). A study of over 1,000 patients with recurrent pregnancy loss reported no difference in the prevalence of abnormal results for evidence-based and investigative diagnostic tests when the diagnostic workup was initiated after two versus three or more losses (6). If clinical intervention is undertaken in the form of investigation after two spontaneous abortions, approximately 1% of pregnant women will require evaluation (3). Even with a history of recurrent pregnancy loss, a patient is more likely to carry her next pregnancy successfully to term than to miscarry. For patients with a history of recurrent pregnancy loss, the risk of subsequent pregnancy loss is estimated to be 24% after two clinically recognized losses, 30% after three losses, and 40% to 50% after four losses (7). These data make clinical study of recurrent pregnancy loss and its treatment difficult because very large groups of patients must be studied to demonstrate the effects of any proposed therapeutic intervention.
Parental chromosomal abnormalities and thrombotic complications of the antiphospholipid antibody syndrome (APS) are the only undisputed causes of recurrent abortion. However, collectively these abnormalities account for less than 10% to 15% of recurrent pregnancy losses. Although the exact proportion of patients diagnosed with a particular abnormality may vary among the populations studied, other associations have been made with anatomic abnormalities (12%–16%), endocrine problems (17%–20%), infections (0.5%–5%), and immunologic factors, including those associated with the APS (20%–50%). Other miscellaneous factors have been implicated and account for approximately 10% of cases. Among women aged 35 or greater who experience recurrent pregnancy loss, spontaneous fetal chromosomal abnormalities are likely to be responsible for the vast majority of losses (8). Even after a thorough evaluation, the potential cause remains unexplained in about one-third to one-half of all cases of recurrent loss (Table 33.1) (3,6,9).