Jorge Correale, Raúl Carrea Institute for Neurological Research, Buenos Aires, Argentina, and colleagues have reported that women with multiple sclerosis who undergo assisted reproduction technology (ART) infertility treatment are at risk for increased disease activity. Results of their study, published in Annals of Neurology, suggested reproductive hormones contribute to regulation of immune responses in autoimmune diseases such as multiple sclerosis.
Women with multiple sclerosis typically do not have diminished fertility except in those treated with cyclophosphamide or high-dose corticosteroids. Research shows that sex hormones and those involved in ovulation (gonadotrophin-releasing hormone, GnRH) play an important role in the development of autoimmune disorders.
To further understand the impact of infertility treatment on multiple sclerosis disease activity, Correale and colleagues analysed clinical, radiological, and immune response data in 16 patients with relapse-remitting multiple sclerosis and who were subject to 26 ART cycles.
The results of their study showed that 75% of patients experienced disease exacerbation following infertility treatment. Relapses were reported in 58% of the cycles during the three month period following ART treatment but no patients had suffered a relapse prior to ART.
Furthermore, ART was associated with a seven-fold increase in risk of multiple sclerosis exacerbation and a nine-fold increase of greater multiple sclerosis disease activity on MRI (compared with the period before the patients started ART). The authors noted that 73% of exacerbations were new symptoms and 27% were attributed to a worsening of pre-existing symptoms.
Deterioration of the disease was associated with three different mechanisms, increase in the production of cytokines (IL-8, IL-12, IFN-γ, and TGF-β by CD4+ T a GnRH-mediated effect); increase in the production of antibodies against de myelin protein MOG, as well as B cell survival factor BAFF and antiapoptotic molecule Bcl-2 levels from purified B cells, these effects were a consequences of the rise of 17-β oestradiol production induced by ART; and authors demonstrated using an in vitro model of the blood-brain-barrier that ART facilitated the penetration of deleterious peripheral blood cells into the central nervous system, an effect mediated by the induction of the molecules IL-8, VEGF and CXCL-12.
“Our findings indicate a significant increase in multiple sclerosis disease activity following infertility treatment,” concluded Correale. “Neurologists should be aware of possible disease exacerbation so they may discuss the benefits and risks of ART with multiple sclerosis patients.”