From the Univ Rennes (M.M., E.L.), EHESP, CNRS, Inserm, ARENES-UMR, France; Univ Rennes (H.T.), Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR, Rennes, France; Pharmacovigilance (A.D., E.P.), Pharmacoepidemiology and Drug Information Centre, Department of Clinical Pharmacology, Rennes University Hospital, France; Neurology Department CRCSEP (E.L.P.), Rennes Clinical Investigation Centre CIC-P, Rennes University Hospital Rennes University INSERM, France; and Department of Gynecology Obstetric and Reproductive Medecine (C.M., S.D.), University Hospital, Rennes, France.
Neurology. 2022 Oct 24;99(17):e1916-e1925. doi: 10.1212/WNL.0000000000201027.
Several studies have shown an increased risk of relapse after in vitro fertilization (IVF) in women with multiple sclerosis (MS), especially when a gonadotrophin-releasing hormone (GnRH) agonist stimulation protocol was used. Our objective was to investigate the risk of relapse after IVF in women with MS, overall and according to stimulation protocol (GnRH agonists vs antagonists), using data from the French national health insurance database.
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 with 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 relapses "after-before," and the delay from IVF to the first relapse. Relapses were identified by an algorithm based on MS-related hospital admissions and the use of corticosteroid therapy. Stimulation protocols and disease-modifying therapies (DMTs) were identified using drug claims. Zero-inflated Poisson regression models adjusted for age at IVF and the presence of DMT were used. A random effect on women was included because women may undergo multiple IVF procedures. Subgroup analyses by stimulation protocol and IVF outcome (pregnancy or failure) were conducted.
A total of 225 women accounting for 338 IVF procedures were included (the mean age at the first IVF 34.6 ± 4.5 years; 36% of women underwent at least 2 IVF procedures during the period). No increase in the risk of relapse after IVF was found overall (before vs after IVF: 0.20 vs 0.18 relapse per patient-year; 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.
The maintenance of DMT until IVF seemed to be a determining factor in reducing the risk of relapse. Women with MS should be reassured because we did not show an increased risk of relapse requiring the use of corticosteroid therapy after IVF neither with GnRH agonists nor with GnRH antagonists.
多项研究表明,接受体外受精(IVF)的多发性硬化症(MS)女性,尤其是使用促性腺激素释放激素(GnRH)激动剂刺激方案的女性,其复发风险增加。我们的目的是使用法国国家健康保险数据库的数据,调查 MS 女性接受 IVF 后复发的风险,包括总体情况以及根据刺激方案(GnRH 激动剂与拮抗剂)。
这项回顾性队列研究纳入了 2010 年 1 月 1 日至 2015 年 12 月 31 日期间在法国接受 IVF 的所有 MS 女性。将 IVF 后 3 个月的暴露期与 IVF 前的未暴露期进行比较,每位女性自身为对照。共考虑了 4 种结局:年化复发率(ARR)、IVF 后复发的比例、“后-前”复发例数的差异,以及从 IVF 到首次复发的延迟。通过基于 MS 相关住院和皮质类固醇治疗使用的算法识别复发。刺激方案和疾病修饰疗法(DMT)使用药物索赔确定。使用调整了 IVF 年龄和 DMT 存在的零膨胀泊松回归模型。由于女性可能接受多次 IVF 手术,因此包含了对女性的随机效应。按刺激方案和 IVF 结局(妊娠或失败)进行了亚组分析。
共纳入了 225 名女性(首次 IVF 时的平均年龄为 34.6 ± 4.5 岁;36%的女性在研究期间至少接受了 2 次 IVF),共进行了 338 次 IVF。总体而言,IVF 后复发风险无增加(前 vs 后 IVF:0.20 vs 0.18 例/患者年;7.7% vs 7.1%的 IVF 女性至少有 1 例复发),且在各亚组中亦无增加。在一直接受 DMT 治疗直到 IVF 的女性中,前、后 IVF 的 ARR 均较低。
在 IVF 前维持 DMT 似乎是降低复发风险的决定因素。我们未发现使用 GnRH 激动剂或 GnRH 拮抗剂后 IVF 后需要使用皮质类固醇治疗的复发风险增加,这应使 MS 女性感到安心。