Inflammatory Activity After Diverse Fertility Treatments: A Multicenter Analysis in the Modern Multiple Sclerosis Treatment Era

Abstract

Background and objectives: Patients with multiple sclerosis (MS) may seek fertility treatment (FT)-including in vitro fertilization (IVF). Variable relapse risk after IVF has been reported in small historical cohorts, with more recent studies suggesting no change in annualized relapse rate (ARR). The objective of this study was to evaluate ARR 12 months pre-FT and 3 months post-FT in a multicenter cohort and identify factors associated with an increased risk of relapse.

Methods: Patients with clinically isolated syndrome (CIS) or MS aged 18-45 years with at least 1 FT from January 1, 2010, to October 14, 2021, were retrospectively identified at 4 large academic MS centers. The exposed period of 3 months after FT was compared with the unexposed period of 12 months before FT. FTs included controlled ovarian stimulation followed by fresh embryo transfer (COS-ET), COS alone, embryo transfer (ET) alone, and oral ovulation induction (OI). The Wilcoxon signed rank test and mixed Poisson regression models with random effects were used to compare ARR pre-FT vs post-FT, with the incidence rate ratio (IRR) and 95% CI reported.

Results: One hundred twenty-four FT cycles among 65 patients with MS (n = 56) or CIS (n = 9) were included: 61 COS-ET, 19 COS alone, 30 ET alone, and 14 OI. The mean age at FT was 36.5 ± 3.8 years, and the mean disease duration was 8.2 ± 5.0 years. Across 80 cycles with COS, only 5 relapses occurred among 4 unique patients within 3 months of treatment. The mean ARR after COS and before was not different (0.26 vs 0.25, p = 0.37), and the IRR was 0.95 (95% CI: 0.52-1.76, p = 0.88). No cycles with therapeutic disease-modifying therapies (DMTs) during COS had 3 months relapse (ARR 0 post-COS vs 0.18 pre-COS, p = 0.02, n = 34). Relapse rates did not vary by COS protocol. Among COS-ET cycles that achieved pregnancy (n = 43), ARR decreased from 0.26 to 0.09 (p = 0.04) within the first trimester of pregnancy. There were no relapses 3 months after ET alone and 1 relapse after OI.

Discussion: In this modern multicenter cohort of patients with MS undergoing diverse FTs, which included 43% on DMTs, we did not observe an elevated relapse risk after FT.

Figure 1. Overview of Common Fertility Treatments, Organized Based on Hypothetical Risk of MS Inflammatory Activity

MS = multiple sclerosis.

Figure 2. Annualized Relapse Rate 3 Months Post-COS vs 12 Months Pre-COS for All Cycles (n = 80)

COS = controlled ovarian stimulation.

Figure 3. Annualized Relapse Rate 3 Months Post-COS vs 12 Months Pre-COS

Forest plot shows incidence rate ratio (IRR) overall and by subgroups. If IRR <1, rate of relapse was lower 3 months after FT. If IRR >1, rate is higher 3 months after FT. If IRR is 1, or close to 1, no difference. IRR was unable to be calculated for the following due to no relapses in these groups: age 37 years or older (n = 32), Black or Hispanic (n = 8), disease duration ≥2 years (n = 32), and patients on therapeutic DMT (n = 34). COS = controlled ovarian stimulation; FTs = fertility treatments.