Fertility, Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorders
Conditions
Keywords
Fertility, Anti-Mullerian Hormone (AMH), Multiple sclerosis (MS), Female, Disease activity
Brief summary
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.
Interventions
BIOLOGICALblood sample to analyse AMH level on the serum
Evaluation of MS/NMOSD inflammatory activity on the serum AMH level (ng/ml)
Sponsors
Observatoire Français de la sclérose en plaques (OFSEP)
Roche Diagnostic Ltd.
ARSEP foundation
University Hospital, Clermont-Ferrand
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Female * Diagnosis of MS (including CIS) or NMOSD * Aged 18 to 35 years old at blood sample collection
Exclusion criteria
* Diagnosis of radiologically isolated syndrome (RIS) * Age less than18 or more than 35. * 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the evaluation of MS/NMOSD inflammatory activity on the serum AMH level (ng/ml) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the potential impact of previous treatments used on AMH level | period before the collection of AMH level | The treatments used will be pooled in highly active treatments (NATALIZUMAB, FINGOLIMOD, PONESIMOD, OFATUMUMAB, ALEMTUZUMAB, CLADRIBINE, OCRELIZUMAB, RITUXIMAB), moderately active (INTERFERON BETA, ACETATE DE GLATIRAMERE, DIMETHYLFUMARATE, LAQUINIMOD, MYCOPHENOLATE MOFETIL, METHOTREXATE) or no treatment. |
Countries
France, Martinique
Outcome results
None listed