The Best Strategies for Managing Women With Recurrent Pregnancy Losses

Peter Kovacs, MD, PhD


December 18, 2013

Management of Women With Recurrent Pregnancy Losses and Antiphospholipid Syndrome

Kwak-Kim J, Agcaoili MS, Aleta L, et al
Am J Reprod Immunol. 2013;69:596-607

The Study

Close to 50% of preclinical pregnancies and on average one fifth to one fourth of clinically diagnosed pregnancies are lost. The spontaneous miscarriage rate is affected by maternal age; whereas it is only around 10% at 30 years of age, it increases to around 40% by 40 years of age.

Recurrent pregnancy loss is defined as 2 or more consecutive first-trimester losses. It is estimated that about 5% of pregnancy losses are recurrent pregnancy losses.[1]

Over 50% of first-trimester losses are due to embryonic chromosome anomalies.[2] Because these genetic defects are typically random errors, a detailed investigation is not warranted after a first episode of pregnancy loss.

However, in cases where the loss is repetitive, a detailed evaluation should be offered. A multidisciplinary approach could identify a well-characterized risk factor for spontaneous abortion in about one half of these cases. The evaluation should explore genetic, anatomical, hormonal, immunologic, hematologic, metabolic, infectious, and lifestyle causes.[1]

About 20% of women with recurrent pregnancy losses will be diagnosed with an immunologic cause, the most common being the antiphospholipid syndrome (APS). Women with APS have positive anticardiolipin, lupus anticoagulant, or anti-beta2-microglobulin antibodies and have a history of thrombotic events or adverse pregnancy outcome (severe growth retardation, severe toxemia, intrauterine fetal demise, or recurrent pregnancy loss). There are diagnostic and therapeutic challenges during the management of these cases.

This review summarizes the most up-to-date knowledge about APS. The authors point out that APS is the most common autoimmune anomaly associated with recurrent pregnancy loss. Patients are identified on the basis of their clinical history and laboratory antibody testing.

There are various mechanisms through which the presence of antiphospholipid antibodies can be linked to pregnancy loss. These antibodies were shown to activate platelets, endothelial cells, and monocytes and, therefore, mediate a procoagulant effect leading to venous or arterial thrombosis. They also influence trophoblast invasion, leading to aberrant placentation that increases the risk for miscarriage. Antiphospholipids also activate the complement system and induce a proinflammatory response via this mechanism.

Various treatments that could limit the activity of these pathologic pathways have been explored. The combination of unfractionated heparin and aspirin was shown to reduce loss rates, and an increase in the chance of a successful live birth has been reported.[3] Both medications mediate antithrombotic and immune-modulating effects, and both of these mechanisms have been proposed to have beneficial effects.

In general, studies have used 5000-10,000 IU unfractionated heparin twice daily combined with 81 mg aspirin. Low-molecular-weight heparin has also been studied but the results are conflicting about its efficacy.[4,5] Steroid therapy and the use of intravenous immunoglobulins have also been tested in the setting of APS, but researchers have reported contradictory results.[6,7]

The most likely reason for the contradictory findings lies in the heterogeneity of the studies. They identify patients on the basis of different criteria, laboratory assays, and titers, and the antibodies tested often differ as well. Therapies are started at various stages of the pregnancies and the workup the patients have undergone is not uniform either.


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