Background and Objectives:Several studies have shown an increased risk of relapse after In Vitro Fertilization (IVF) in women with Multiple Sclerosis (MS), especially when a GnRH agonists stimulation protocol was used. Our objective was to investigate the risk of relapse after IVF in women with multiple sclerosis, overall and according to stimulation protocol (GnRH agonists vs antagonists), using data from the French national health insurance database.Methods:This retrospective cohort study included all women with MS who have benefited from IVF between January 1, 2010 and December 31, 2015 in France. Three-month exposed periods after IVF were compared to unexposed periods before IVF, each woman being her own control. Four outcomes were considered: annualized relapse rate (ARR), proportion of IVF with relapse, difference in the number of relapse “after – before” and the delay from IVF to the first relapse. Relapses were identified by an algorithm based on MS-related hospital admissions and use of corticosteroid therapy. Stimulation protocols and disease-modifying therapies (DMT) were identified using drugs claims. Zero-inflated Poisson regression models adjusted for age at IVF and presence of DMT were used. A random effect on the woman was included because women may have multiple IVF procedures. Subgroup analyses by stimulation protocol and IVF outcome (pregnancy or failure) were conducted.Results:A total of 225 women accounting for 338 IVF were included (mean age at first IVF 34.6 ± 4.5 years; 36% of women had at least two IVF during the period). No increase in the risk of relapse after IVF was found overall (before vs. after IVF: respectively 0.20 vs. 0.18 relapse per patient-year; resp. 7.7% vs. 7.1% of IVF with women having at least one relapse) and in subgroups. A lower ARR before and after IVF was observed among women who remained treated until IVF.Discussion:The maintenance of DMT until IVF appeared to be a determining factor in reducing the risk of relapse. Women with MS should be reassured as we did not show an increased risk of relapse requiring use of corticosteroids therapy after IVF neither with GnRH agonists nor with GnRH antagonists.