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Increase in multiple sclerosis activity after assisted reproduction technology

Authors

  • Jorge Correale MD,

    Corresponding author
    1. Department of Neurology, Institute for Neurological Research Dr Raúl Carrea, Foundation Against Neurological Disease in childhood (FLENI), Buenos Aires, Argentina
    • Raúl Carrea Institute for Neurological Research, (FLENI), Montañeses 2325, (1428) Buenos Aires, Argentina
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  • Mauricio F. Farez MD, MPH,

    1. Department of Neurology, Institute for Neurological Research Dr Raúl Carrea, Foundation Against Neurological Disease in childhood (FLENI), Buenos Aires, Argentina
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  • María C. Ysrraelit MD

    1. Department of Neurology, Institute for Neurological Research Dr Raúl Carrea, Foundation Against Neurological Disease in childhood (FLENI), Buenos Aires, Argentina
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Abstract

Objective:

Our objective was to evaluate risk of exacerbations in multiple sclerosis (MS) patients undergoing assisted reproduction technology (ART) infertility treatment.

Methods:

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.

Results:

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.

Interpretation:

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. ANN NEUROL 2012;72:682–694

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