Recurrent abortion is the spontaneous loss of two consecutive, or three total, ﬁrst-trimester pregnancies regardless of the outcome of other pregnancies. (Some deﬁnitions restrict this deﬁnition to three consecutive losses.) This is estimated to affect between 0.4% and 0.8% of reproductive-age women. Problems with the chromosomal makeup of the embryo, the hormonal environment of the pregnancy, or physical attributes of the uterus or endometrium may play a role in these losses. Risk factors for recurrent pregnancy loss are the same as those associated with single spontaneous abor- tion, including increasing maternal and paternal age, certain medical illnesses like uncontrolled diabetes mellitus and thrombophilias, and autoimmune disorders. In 40% of cases, no risk factor or cause will be identiﬁed. In general, about 70% of these patients will have a subsequent normal pregnancy without intervention.
When pregnancy losses occur early in gestation, there is a greater likelihood that a chromosomal abnormality is the cause, whereas for later abortions, a maternal cause such as a uterine anomaly is more likely. Although most chromosomal abnormalities result from disorders of meiosis in gamete formation or in mitosis after fertilization, 5% of couples that experience recur- rent abortion have a detectable parental chromosomal balanced abnormality. For this reason, karyotyping of both parents is recommended when recurrent early abortions have occurred. When available, karyotyping of the abortus may be helpful but requires fresh tissue, specialized transport media, and appropriate laboratory capabilities. Those with parental chromosomal anomalies may be offered donor oocytes or artiﬁcial insemination with donor sperm to overcome the problem.
Two-thirds of recurrent abortions occur after 12 weeks’ gestation, which suggests that maternal or environmental factors play a larger role in this process than do genetic conditions. Surgically correctable uterine abnormalities, an incompetent cervix, or intrauterine septa or synechiae are the most common uterine abnormalities associated with early pregnancy loss. Indeed, uterine anomalies are found in 15% to 25% of women with recurrent abortion. When uterine anomalies are suspected, hysteroscopy is preferred for both diagnosis and therapy. Uterine anomalies or submucous ﬁbroids may be treated in this way, although care must be taken to recognize the possibility of continued failure for other reasons and the possible impact on future delivery options made by such treatment.
The possibility of systemic factors such as hypothyroidism, coagulopathy or thrombophilia, or immunologic factors (e.g., lupus anticoagulant) as a cause of recurrent losses should be evaluated when there is reason for clinical suspicion or other evaluations have proven inconclusive. When immunologic factors are present, the use of low-dose aspirin and subcutaneous heparin (5000 units twice daily) has reduced the rate of subsequent loss.
The evaluation of patients with recurrent pregnancy losses starts with a history and physical examination with an eye toward cervical incompetence, drug or chemical exposures, gastrointestinal diseases, a family history of miscarriages, birth defects, or thrombosis. The history and physical examination often direct the appropriate laboratory evaluation, including studies of thyroid-stimulating hormone and antithyroid antibodies, or a thrombophilia proﬁle. If all these tests are normal, an evaluation of the uterine cavity by sonohysterography or hysteroscopy should be considered. It is not necessary to obtain endometrial bacteriologic cultures or perform human leukocyte antigen typing of the woman or her partner.
Therapeutic intervention for recurrent pregnancy loss is always based on the underlying cause. Progesterone and thyroid supplements have not been shown to reduce the risk of pregnancy loss.