No Evidence of Elevated MS Relapse Risk Following Fertility Treatments

Edith Graham, MD, assistant professor of neurology, Northwestern University Feinberg School of Medicine

Using a cohort of patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS), investigators found no increased risk of relapse with fertility treatments (FT), including controlled ovarian stimulation (COS) followed by egg retrieval (ER), embryo transfer (ET), and in vitro fertilization (IVF).

In total, 5 relapses in 4 unique patients occurred within 3 months post-FT after observing 110 cycles of FT in 55 individuals with either MS (n = 48) or CIS (n = 7). Presented at the 2022 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, October 26-28, in Amsterdam, Netherlands, the mean annualized relapse rate (ARR) was 0.18 post-FT compared with 0.23 pre-FT (P = .14).

Lead investigator Edith Graham, MD, assistant professor of neurology, Northwestern University Feinberg School of Medicine, and colleagues included patients ages 18 to 45 years with at least one FT cycle from 1/1/10 to 9/14/21 who were retrospectively identified at 4 large US academic centers. ARR 12 months pre-FT and 3 months post-FT was compared using Wilcoxon signed-rank test for paired samples and mixed Poisson regression models with random effects for repeated patient cycles.

IVF, which included COS, ER, and ET together, was the most common FT, used in 56% (n = 61) of the cycles. ET only and COS only accounted for 27% (n = 30) and 17% (n = 19) of the remaining cycles, respectively. Before and after FT treatment, the incidence rate ratio for the ARR was 0.80 (95% CI, 0.44-1.44; P = .46). Although there was an ARR of 0.17 pre-FT, Graham et al observed no cycles while on a therapeutic disease-modifying therapy that led to 3-month relapse (P = .01). Among the cycles without therapeutic DMT, ARR was 0.30 post-FT compared with 0.26 pre-FT (P = .81).

IRR was elevated for those who underwent cycles of treatment with ER without ET (IRR, 1.71; 95% CI, 0.68-4.35; P = .26) and those with at least 2 stimulations within 3 months (IRR, 4.0; 95% CI, 0.85-18.8; P = .08). There was no significant difference in relapse rates for those on COS protocol cycles. Additionally, ARR decreased from 0.26 to 0.09 in cycles that achieved pregnancy (n = 43), equating to an IRR of 0.36 (95% CI, 0.12-1.14; P = .08).

Previous studies have shown that some types of fertility treatment may increase the risk of relapses in women with MS, with relapse rates increasing in the first 3 months after IVF; however, a recent 2019 study led by Riley Bove, MD—the senior author for this new research—did not find an increase in relapses with the use of FT. In her other study, she and her colleagues evaluated the risk of relapses after assistant reproductive technologies (ART) in an unpublished cohort (Boston: 22 ART cycles), data pooled from Boston and 5 published studies (164 cycles) and a meta-analysis of all case series published by 2017 (220 cycles).²

In the Boston cohort, mean ARR was not higher after ART than before (mean, 0.18 [±0.85] vs 0.27 [±0.55]; P = .58). In the pooled analysis, ARR was significantly higher after ART for all clinical scenarios, including varying ART protocols (P <.01 for each). Furthermore, the meta-analysis confirmed an increased ARR after ART (mean difference, 0.92; 95% CI, 0.33-1.51; P = .01).

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REFERENCES
1. Graham E, Bakkensen J, Anderson A, et al. Relapse risk after fertility treatments in women with MS: a multicenter analysis of inflammatory activity. Presented at: 2022 ECTRIMS annual meeting; October 26-28; Amsterdam, Netherlands. Abstract O040
2. Bove R, Rankin K, Lin C, et al. Effect of assisted reproductive technology on multiple sclerosis relapse: case series and meta-analysis. Mult Scler. 2020;26(11):1410-1419. doi:10.1177/1352458519865118.