Research: Having a Baby. Fertility treatment increases chances of MS exacerbation

Epub: Correale et al. Increase in multiple sclerosis activity after assisted reproduction technology. Ann Neurol. 2012 Oct 3. doi: 10.1002/ana.23745.

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.

"Provided these results are confirmed this study is important for several reasons. Firstly, it is telling us something about the immunology of MS; hormones that are used for fertility treatment appear to exacerbate MS. Secondly, and more importantly, MSers who are having fertility treatment need to know that there is a potential risk that the treatment will exacerbate their MS, i.e. trigger relapses. I have personal experience of this; two MSers under my care who have had fertility treatment had relapses after IVF. My German colleagues are now putting MSers who want to fall pregnant or want to have IVF on glatiramer acetate to counteract this. The latter is based on the emerging data, from several MS registers, that suggests glatiramer acetate is safe in pregnancy."