Etanercept immunotherapy in women with a history of recurrent miscarriage

OBJECTIVE: The aim of the study was to determine pregnancy outcome after etanercept immunotherapy in women with a history of at least three recurrent miscarriage (RM) or failed IVF. Etanercept is a tumor necrosis factor antagonist with anti-inflammatory effects. Its major mode of action is to suppress TNF-alpha, a Th-1 embryotoxic cytokine produced by activated natural killer (NK) cells. DESIGN: We studied pregnancy outcome in RM women with increased NK cell number and/or activity before conception. MATERIALS AND METHODS: We studied pregnancy outcome in 30 women with increased NK cell number and/or activity before conception. Women received 4 doses (25 mg) of etanercept twice weekly before conception. The consent for the study from the Bioethics Committee of the Military Institute of Medicine and from the patients was obtained. Natural killer cell activity was measured using flow cytometry. In addition, the following peripheral blood NK cells' surface antigens: CD16, CD56 and T reg were studied using flow cytometry, before treatment and 2 weeks after the last etanercept dose. RESULTS: We determined that there is a significantly lower natural killer cell activity after etanercept therapy in the study women (P<0.05). Moreover, there is a positive correlation between decreased natural killer cell activity after etanercept therapy and successful pregnancy in the study women (r>0.5, P<0.05). There were no significant differences in T reg level before and after etanercept therapy (P>0.05). CONCLUSION: Etanercept therapy might be effective treatment for women with increased NK cell activity. Regulation of immune system activity may underlie possible effect of such therapy.