Evaluation of the Impact of Multiple Sclerosis and Its Treatments on Women Fertility
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 800
- 试验地点
- 27
- 主要终点
- the evaluation of MS/NMOSD inflammatory activity on the serum AMH level (ng/ml)
研究概览
简要总结
CONTEXT A desire for pregnancy is common in young patients with multiple sclerosis (MS). The impact of MS on women fertility is debated, and the impact of disease-modifying therapies (DMTs) on fertility is not well known. Antimüllerian hormone (AMH) is a representative biomarker of ovarian reserve that can be used to explore this issue.
OBJECTIVES To examine the impact of MS activity and related DMTs on ovarian reserve measured by serum AMH level.
METHODOLOGY Retrospective multicentre study based on clinical and blood samples from patients included in the OFSEP cohort. A serum sample from more than 800 MS and 96 NMOSD women aged 18-35 will be available for AMH dosing. The results obtained will be interpreted taking into account the age, the inflammatory activity of the disease, the disability (EDSS) and the previous and current DMTs used.
STATISTICAL ANALYSIS Spearman correlation coefficient will be calculated in univariate analysis between serum AMH level and number of relapses that occurred during the 2 years before blood sample collection. For multivariable analysis, multiple mixed linear regression will be performed with AMH level as dependant outcome and number of relapses, age, DMTs (highly active, moderately active or no treatment), disease duration and disability (measured using EDSS) as independent variables. The center will be considered as random-effect. For AMH level categorized as normal or not, mixed logistic regression will be performed with aforementioned covariates. These analyses will be completed by a mediation analysis between AMH level, number of relapses and DMTs with age, EDSS and disease duration as adjustments covariates.
EXPECTED RESULTS :
Evaluation of the potential relationship between AMH levels and MS or NMOSD activity at the first years of the illness.
Evaluation of the potential impact of MS and NMOSD treatments on ovarian reserve.
Optimization of the indications of fertility preservation for MS and NMOSD female patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of MS (including CIS) or NMOSD
- •Aged 18 to 35 years old at blood sample collection
排除标准
- •Diagnosis of radiologically isolated syndrome (RIS)
- •Age less than18 or more than
- •History of ovarian surgery
- •Endometriosis
- •Hypergonadotropin amenohrrea
- •Any associated known autoimmune disease other than MS
- •Previous MS treatment with immunosuppressive agents such as azathioprine, cyclophosphamide, mitoxantrone, bone marrow transplantation
- •Previous treatment with gonadotoxic drugs (eg chemotherapy)
研究组 & 干预措施
MS / NMOSD female patients
MS / NMOSD female patients , aged between 18 and 35, with or without MS treatment
干预措施: blood sample to analyse AMH level on the serum (Biological)
结局指标
主要结局
the evaluation of MS/NMOSD inflammatory activity on the serum AMH level (ng/ml)
时间窗: period of 2 years before blood samples
Disease activity will be evaluated on the number of relapses that occurred during the 2 years before blood sample collection and total number of relapses, taking disease duration into account. The measurement of AMH level will be performed using the electrochemiluminescence method with a Cobas® e411 analyzer (Roche Diagnostics, Meylan, France). This immunoassay is based on a sandwich format between the analyte and the two antibodies: a biotinylated AMH-specific mouse monoclonal capture antibody and a second ruthenium-labeled AMH mouse monoclonal antibody. This assay is a fully automated, robust and precise method. Repeatability and intermediate precision calculated on serum samples range from 1.1% to 1.8% and 3.3% to 4.4%, respectively. The assay time is 18 minutes and the measuring range is from 0.01 to 23 ng/ml. The threshold of inf at1 ng/ml will be considered to be a proof of severe decrease in ovarian reserve
次要结局
- Evaluation of the potential impact of previous treatments used on AMH level(period before the collection of AMH level)