Multiple sclerosis and related disorders · 2026
Challenging historical associations and reassuring women: an updated meta-analysis of multiple sclerosis relapse risk following assisted reproductive technology.
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Mohamed Mohamed I, Thabet Monica Youssef, Nasr Nada, Nada Mona Af
Аннотация
BACKGROUND: Historical studies suggested that assisted reproductive technologies (ARTs) may increase relapse rates in women with multiple sclerosis (WwMS). We conducted an updated systematic review and meta-analysis to clarify the effects of ART on MS relapse risk and assess whether ART is associated with incident MS in previously healthy women.
METHODS: Following PRISMA guidelines, we searched four databases until May 2026. Cohorts, case-controls, and case series (>5 participants) evaluating relapse risk after ART or incident MS following ART were eligible. Random-effects meta-analyses pooled adjusted rate ratios (aRRs), with prespecified subgroup and sensitivity analyses. Risk-of-bias was assessed using the Newcastle-Ottawa Scale.
RESULTS: Twelve studies (11 of good quality), including four nationwide cohorts, met the criteria. Ten assessed relapse risk (n = 680); 2 assessed incident MS risk (n = 586,656). We found an insignificant relapse risk with minimal heterogeneity (95% CI 0.85-1.39; I²=4.6%). No significant increase in risk was observed among women not receiving disease-modifying therapies (DMTs) during fertility treatment, with gonadotropin-releasing hormone (GnRH) agonist or GnRH antagonist protocols. Women achieving pregnancy following ART experienced significantly fewer relapses (aRR 0.50, 95% CI 0.29-0.84); failed ART showed a nonsignificant trend towards increased relapse risk (aRR 1.31, 95% CI 0.96-1.79). ART was not associated with an increased risk of incident MS in 2 studies.
INTERPRETATION: Contemporary evidence suggests that ART does not independently increase relapse risk in WwMS or the risk of developing de novo MS. These findings support individualized fertility counselling focused on optimizing disease control rather than discouraging ART. Prospective studies are warranted.
METHODS: Following PRISMA guidelines, we searched four databases until May 2026. Cohorts, case-controls, and case series (>5 participants) evaluating relapse risk after ART or incident MS following ART were eligible. Random-effects meta-analyses pooled adjusted rate ratios (aRRs), with prespecified subgroup and sensitivity analyses. Risk-of-bias was assessed using the Newcastle-Ottawa Scale.
RESULTS: Twelve studies (11 of good quality), including four nationwide cohorts, met the criteria. Ten assessed relapse risk (n = 680); 2 assessed incident MS risk (n = 586,656). We found an insignificant relapse risk with minimal heterogeneity (95% CI 0.85-1.39; I²=4.6%). No significant increase in risk was observed among women not receiving disease-modifying therapies (DMTs) during fertility treatment, with gonadotropin-releasing hormone (GnRH) agonist or GnRH antagonist protocols. Women achieving pregnancy following ART experienced significantly fewer relapses (aRR 0.50, 95% CI 0.29-0.84); failed ART showed a nonsignificant trend towards increased relapse risk (aRR 1.31, 95% CI 0.96-1.79). ART was not associated with an increased risk of incident MS in 2 studies.
INTERPRETATION: Contemporary evidence suggests that ART does not independently increase relapse risk in WwMS or the risk of developing de novo MS. These findings support individualized fertility counselling focused on optimizing disease control rather than discouraging ART. Prospective studies are warranted.