Increase in multiple sclerosis activity after assisted reproduction technology.

Abstract

Our objective was to evaluate risk of exacerbations in multiple sclerosis (MS) patients undergoing assisted reproduction technology (ART) infertility treatment. Sixteen patients with relapsing-remitting MS subjected to 26 ART treatment cycles receiving gonadotropin-releasing hormone (GnRH) agonists and recombinant follicle-stimulating hormone were studied prospectively. The baseline study period encompassed 12 months prior to the first cycle and 9 months after final ART cycle. Neurological examinations, brain magnetic resonance imaging (MRI), and immunology testing were conducted every 3 months. Anti-myelin-oligodendrocyte glycoprotein (MOG) antibody production, interleukin (IL)-4, IL-8, IL-10, IL-12, IL-17, interferon (IFN)-γ, and transforming growth factor (TGF)-β secretion by myelin basic protein- and MOG-peptide-specific T cells, as well as ex vivo isolated peripheral blood mononuclear cells (PBMCs), were studied using enzyme-linked immunospot. vascular endothelial growth factor (VEGF) production by PBMCs was assessed using enzyme-linked immunosorbent assay. ART was associated with a 7-fold increase in risk of MS exacerbation, and a 9-fold increase in risk of enhanced disease activity on MRI. Worsening was associated with higher number of cells producing IL-8, IL-12, IFN-γ, and TGF-β, as well as increased VEGF production by CD4(+) T cells and CXCL-12 plasma levels, all GnRH-mediated effects. A rise in 17-β estradiol production associated with ART increased anti-MOG antibody titers, as well as B-cell survival factor BAFF (B-cell activating factor) and antiapoptotic molecule Bcl-2 levels from purified CD19(+) B cells. Finally, ART facilitated PBMC transmigration across an in vitro blood-brain barrier model, an effect mediated by IL-8, VEGF, and CXCL-12. Results indicate a significant increase in MS disease activity in patients receiving ART, a risk that neurologists should be aware of. Reproductive hormones appear to exert an important role in regulating immune responses during the course of autoimmune diseases.