Evaluation of the Impact of Multiple Sclerosis and Its Treatments on Women Fertility

NCT07164924 | Completed

• 1 other identifier: 2024-CF243
• Study Type: observational
• Target: 800
• Locations: 2 countries
• Sites: 27

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.

Conditions

Multiple Sclerosis; Neuromyelitis Optica Spectrum Disorders; Fertility

Keywords

Fertility; Anti-Mullerian Hormone (AMH); Multiple sclerosis (MS); Female; Disease activity

Outcome Measures

Primary Outcomes (1)

• the evaluation of MS/NMOSD inflammatory activity on the serum AMH level (ng/ml)

  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

  period of 2 years before blood samples

Secondary Outcomes (1)

• Evaluation of the potential impact of previous treatments used on AMH level

  period before the collection of AMH level

Study Arms (1)

MS / NMOSD female patients

MS / NMOSD female patients , aged between 18 and 35, with or without MS treatment

Biological: blood sample to analyse AMH level on the serum

Interventions

blood sample to analyse AMH level on the serum BIOLOGICAL

Evaluation of MS/NMOSD inflammatory activity on the serum AMH level (ng/ml)

MS / NMOSD female patients

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• Female
• Diagnosis of MS (including CIS) or NMOSD
• Aged 18 to 35 years old at blood sample collection

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead
• Observatoire Français de la sclérose en plaques (OFSEP): collaborator
• Roche Diagnostic Ltd.: collaborator
• ARSEP foundation: collaborator

Study Sites (27)

CHU Amiens

Amiens, France

Location

CHU Besancon

Besançon, France

Location

CHU Bordeaux

Bordeaux, France

Location

CHU Caen

Caen, France

Location

CHU Clermont-Ferrand

Clermont-Ferrand, 63000, France

Location

AP-HP - Créteil

Créteil, France

Location

CHU Dijon

Dijon, France

Location

CHU Grenoble

Grenoble, France

Location

CHU Lille

Lille, France

Location

CHU Limoges

Limoges, France

Location

Hospices Civils de Lyon

Lyon, France

Location

AP-HM

Marseille, France

Location

CHU Montpellier

Montpellier, France

Location

CHU Nancy

Nancy, France

Location

CHU Nantes

Nantes, France

Location

CHU Nice

Nice, France

Location

CHU Nîmes

Nîmes, France

Location

Hôpital de la Pitié-Salpêtrière

Paris, France

Location

Hôpital Fondation Rothschild

Paris, France

Location

Hôpital Saint Antoine

Paris, France

Location

CHI Poissy- Saint-Germain-en-Laye

Poissy, France

Location

CHU Poitiers

Poitiers, France

Location

CHU Rennes

Rennes, France

Location

CHU Strasbourg

Strasbourg, France

Location

CHU Toulouse

Toulouse, France

Location

CHU Tours

Tours, France

Location

CHU Fort-de-France

Fort-de-France, Martinique

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

serum for antimüllerian l(AMH) level

MeSH Terms

Conditions

Multiple Sclerosis; Neuromyelitis Optica

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases

Study Officials

• Pierre Clavelou

  CHU de Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2025
• First Posted: September 10, 2025
• Study Start: January 1, 2018
• Primary Completion: December 8, 2024
• Study Completion: December 8, 2024
• Last Updated: September 10, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (26); MA (1)