Effect of assisted reproductive technology on multiple sclerosis relapses: Case series and meta-analysis

Abstract

Background: Five case series reported increased relapse risk after assisted reproductive technologies (ART) in women with multiple sclerosis (MS), but small numbers and heterogeneous study design limit broader conclusions. Objective: To evaluate the risk of relapses after ART in an independent case series and in aggregated analyses of existing studies. Methods: We compared annualized relapse rate (ARR) in the 3 months after, and 12 months before, ART in (1) an unpublished cohort (Boston: prospectively collected relapses; 22 ART cycles), (2i) data pooled from Boston and five published studies (164 cycles), and (2ii) a meta-analysis of all case series published by 2017 (220 cycles; PRISMA and MOOSE guidelines). Results: In the Boston cohort, mean ARR was not higher after ART than before (mean: 0.18 ± 0.85 vs 0.27 ± 0.55, p = 0.58). In the pooled analyses, ARR was significantly higher after ART for all clinical scenarios, including varying ART protocols ( p ⩽ 0.01 for each). The meta-analysis confirmed an increased ARR after ART (mean difference (MD) = 0.92, 95% confidence interval (CI) = [0.33, 1.51], p = 0.01). Conclusion: These pooled data support an increase in ARR following ART. Reasons for local variation in ARR after ART, and consideration of MS treatments during conception attempts, will be pursued.

Sex effects across the lifespan in women with multiple sclerosis

“…51–55 Whereas the Boston case series did not have higher ARR after ART compared with before, the overall meta-analysis including this cohort confirmed increased ARR after ART, with a mean ARR increase of 0.92 [95% confidence interval (CI) 0.33–1.51]. 50 On the other hand, Guzman-Soto et al reported that leuprolide acetate, a synthetic analogue of GnRH used in IVF, has a neurotrophic effect on neurofilament, myelin basic protein expression, and axonal morphometry in EAE, thus opening horizons for studying protocols of ART in MS. 56…”

“…52 Similarly, another study, wherein women with MS received GnRH agonist or antagonist, followed by FSH, found that the annualized relapse rate (ARR) increased during 3 months following ART, with correlation to GnRH agonist use and IVF failure. 53 A recent meta-analysis by Bove et al 50 combined five published studies and reported a case series (n = 12). [51][52][53][54][55] Whereas the Boston case series did not have higher ARR after ART compared with before, the overall meta-analysis including this cohort confirmed increased ARR after ART, with a mean ARR increase of 0.92 [95% confidence interval (CI) 0.33-1.51].…”

The road to conception for women with multiple sclerosis

“…28,29 It is important to consider that counseling should be given about the possibility of an increased risk for MS relapse after ART. 29,30 As with most research, CANPREG-MS has benefits and limitations. As previously stated, this is a real world scenario with no restrictions on a woman's age, disability, MS duration, therapy, etc.…”

Pharmacotherapeutic considerations in women with multiple sclerosis

“…Observational studies and clinical reports have provided evidence that ART increases the risk of relapse, number of new or enlarging T2 lesions and gadolinium-enhancing lesions -particularly in the first three months if the ART has been unsuccessful [26,27]. Gonadotropin-releasing hormone (GnRH) agonists stimulate immune cell proliferation; cytokine, chemokine and endothelial growth factor production; and estrogen levels.…”