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.

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)

Women, with age between 18 at 35, with a diagnosis of MS or NMOSD , present in EDMUS database, which has a blood sample in the OFSEP cohort