Ovarian Reserve and Semen Parameters Evolution During Adjuvant Therapy in Melanoma

Study Overview
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Brief Summary
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Prospective multicentric study including women aged 18 to 35 and men aged 18 to 45 during their visit to centers for the study and storage of human sperm and eggs (CECOS). Subjects will be included before adjuvant treatment initiation (T0) and immediately after treatment (approximately 1 year after initiation, T1), and, in late post treatment (1 year after treatment cessation, T2). Expected results: This study will evaluate the evolution of AMH, AFC, and semen parameters in our cohort of melanoma patients treated with anti-PD-1 and targeted therapy in an adjuvant settings.

Detailed Description
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To the best of our knowledge, no data is available in humans on the impact of anti-PD-1 immunotherapies and therapies targeting the MAP kinase pathway, in adjuvant settings, on ovarian reserve and semen quality. Main objective: to measure pre-treatment (T0) and immediate post-treatment (T1) evolution of anti-Müllerian hormone (AMH) levels reflecting the ovarian reserve in women, and of the total motile sperm count per ejaculate in men, in patients of childbearing age treated with anti-PD-1 immunotherapy or targeted therapies in an adjuvant situation for melanoma at high risk of recurrence. Method: Prospective multicentric study including women aged 18 to 35 and men aged 18 to 45 during their visit to centers for the study and storage of human sperm and eggs (CECOS). Subjects will be included before adjuvant treatment initiation (T0) and immediately after treatment (approximately 1 year after initiation, T1), and, in late post treatment (1 year after treatment cessation, T2). At each of their visit to CECOS (T0, T1 and T2), the women will have an AMH assay and an antral follicle count (AFC) by ultrasound while the men will perform a semen analysis (count, spermocytogram and staining with aniline blue for analysis of chromatin condensation). A standardized questionnaire aimed at collecting data about factors that may alter fertility will be submitted at each of these visits. Expected results: This study will evaluate the evolution of AMH, AFC, and semen parameters in our cohort of melanoma patients treated with anti-PD-1 and targeted therapy in an adjuvant settings.

Official Title
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Ovarian Reserve and Semen Parameters Evolution During Adjuvant Therapy in Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Other: biological sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have provided a signed, dated and written consent prior to any specific procedures, sampling and analyses Patients with valide Health Inssurance Scheme Female between 18 and 35 years old and male between 18 and 45 years old During the 2 months before the introduction of an approved regimen of adjuvant anti-PD-1 immunotherapy or targeted therapy for an high-risk of reccurence melanoma Exclusion Criteria: Individuals deprived of liberty or placed under the authority of a tutor Patients unable to understand, read and/or sign an informed consent History of cytotoxic treatment before T0 that can alterate the studied parameters In male, totale motile sperm count per ejaculate inferior to 39 millions at T0 In women, an age-specific AMH level inferior to the 10th percentile at T0 Any condition which in the Investigator's opinion would jeopardize compliance with the protocol of the study Patients that will received an investigational treatment during the study timeframe (an observational research is allowed)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Immunotherapy cohort<br>Patient that received adjuvant immunotherapy | Other: biological sampling<br>* Biological sampling: blood and semen<br>|
| Targeted therapy<br>Patient that received adjuvant targeted therapy | Other: biological sampling<br>* Biological sampling: blood and semen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| measurement of biological parameters : Anti-Müllerian hormone (AMH) levels in women | change in Anti-Müllerian hormone (AMH) levels in women | T1 (=Day0 + 12 months) | 
| measurement of biological parameters : Change in sperm motility count in men | Change in sperm motility count per ejaculate in men | T1 (=Day0 + 12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| measurement of biological parameters : Antral follicle count in women | change in antral follicle count in women | T0 = Day 0 = treatment initiation; T1 = Day0 + 12 months; T2 = T1 + 12 months. | 
| measurement of biological parameters : levels of spermatozoids with sperm chromatin abnormalities | change of rate of spermatozoids with sperm chromatin abnormalities | T0 = Day 0 = treatment initiation; T1 = Day0 + 12 months; T2 = T1 + 12 months. | 
| measurement of biological parameters : Change in sperm count | Change in sperm count (spermogram) during time | T0 = Day 0 = treatment initiation; T1 = Day0 + 12 months; T2 = T1 + 12 months. | 
| measurement of biological parameters : Change in sperm motility count | Change in sperm motility count (spermogram) | T0 = Day 0 = treatment initiation; T1 = Day0 + 12 months; T2 = T1 + 12 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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melanoma, ovarian reserv, semen parameters, fertility, adjuvant