Other immunoregulating therapies theoretically useful in treating recurrent pregnancy loss include the use of cyclosporine, pentoxifylline, and nifedipine, although maternal and fetal risks with these agents preclude their clinical use. Plasmaphoresis has also been used to treat women with recurrent abortion and antiphospholipid antibodies (420). Generalized immunosuppression with corticosteroids, such as prednisone, has been advocated during pregnancy for women with recurrent losses and chronic intervillositis and those with recurrent pregnancy loss and APS (421). Although corticosteroids have shown some treatment promise in these patients, maternal and fetal side effects and the availability of alternative therapies have limited their use (421,422). That said, in response to successful use of prednisolone in a woman with 10 prior losses, Quenby et al. have demonstrated that such treatment decreases the number of uterine NK cells in the peri-implantation decidua among women with a history of recurrent loss and have plans for a trial of therapy using live birth as a secondary outcome (423–425). The efficacy and side effects of prednisone plus low-dose aspirin was examined in a recent, large, randomized, placebo-controlled trial treating patients with autoantibodies and recurrent pregnancy losses. Pregnancy outcomes for treated and control patients were similar; however, the incidence of maternal diabetes and hypertension and the risk of premature delivery were all increased among those treated with prednisone and aspirin (426).
Antithrombotic Therapy Therapy for patients with recurrent pregnancy losses associated with either APS or other thrombophilic disorders has now shifted toward the use of antithrombotic medications. Unlike immunosuppressive treatments, this approach appears to address the effect (hypercoagulability), but not the underlying cause (e.g., genetic, APS) of recurrent pregnancy loss. However, there are reports that heparin, one typical anticoagulant, may exert direct immunomodulatory effects by binding to antiphospholipid antibodies and may decrease movement of inﬂammatory cells to sites of alloantigen exposure (427,428). The combined use of low-dose aspirin (75 to 80 mg per day) and subcutaneous unfractionated heparin (5,000 to 10,000 units twice daily) during pregnancy has been best studied among women with APS and appears to be efficacious (429–433). A typical regimen for women with antiphospholipid antibody syndrome would include use of aspirin (80 mg every day) beginning with any attempts to conceive. After pregnancy has been confirmed, 10,000 IU unfractionated sodium heparin is administered subcutaneously twice daily, throughout gestation. An aPTT should be obtained weekly and dosages of heparin should be adjusted until anticoagulation is achieved. Patients using this therapy should be treated in conjunction with a perinatologist because of their increased risks for preterm labor, premature rupture of the membranes, intrauterine growth restriction, intrauterine fetal demise, and pre-eclampsia. Other potential risks include gastric bleeding, osteopenia, and abruptio placenta.
Attempts have recently been made to extend the finding that antithrombotic therapy is efficacious when used to treat patients with APS and recurrent pregnancy loss in a number of directions. These directions include the use of low-molecular weight heparins (LMWH), the use of antithrombotic therapy in non-APS patients with thrombophilia and recurrent pregnancy loss, and even its use among recurrent pregnancy loss patients without thrombophilia (unexplained recurrent losses).