OBJECTIVE: The objective was to evaluate risk of exacerbations in MSers undergoing assisted reproduction technology (ART) infertility treatment.
METHODS: 16 relapsing-remitting MSers 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 MSers and neurologists should be aware of. Reproductive hormones appear to exert an important role in regulating immune responses during the course of autoimmune diseases.
Oh dear. I had fertility treatment over around a 5 year period 15 to 20 years ago. Nobody connected my MS diagnoses to it. What news about taking HRT? Best Pam
Prof G,Does it tell us anything about what comes first – damage then inflammation or inflammation then damage?What happened to the hormone trials (for women)? I recall that they were hijacked by copaxone?A favour – can you find out what happened to anti-lingo anti-body when you are at ECTRIMS. It's gone very quiet whicg I suspect could suggest it wasn't successful.
Does it tell us anything about what comes first – damage then inflammation or inflammation then damage?No I do not think so.Anti-LINGO trial was phase I so it only says if it is safe or not. But will leave that to Prog G to Snoop.
It seems the IVF treatment has a number of biologic effects – increase in MOG antibodies, increase in IL, increase in VEGF (something associated with the vasculature), etc. Any idea which one(s) are responsible for the worsening MS?
Re: "It seems the IVF treatment has a number of biologic effects – increase in MOG antibodies, increase in IL, increase in VEGF (something associated with the vasculature), etc. Any idea which one(s) are responsible for the worsening MS?"Unfortunately, I don't have a clue. I would also wait for this study to be confirmed.