Impact of Folates in the Care of the Male Infertility

Study Overview
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Brief Summary
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Unexplained male infertility is increasing, and, nowadays, the investigators only can propose palliative treatment, as In VITRO Fertilization (IVF). The folate metabolism is a key for the maintenance of genome integrity. A dysfunction in this pathway can be responsible of spermatogenesis defects, and further, of infertility. Few assays have shown that folate treatment can improve sperm parameters and fertility, till 30% in some of theses studies. The purpose of the investigators study is to demonstrate the impact of folates treatment on improvement of sperm parameters and on the rate of success of in VITRO fertilization procedures.

Detailed Description
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The folate impact in the treatment of male infertility will be reviewed by this large multicentric randomized controlled double-blind study comparing 2 parallel groups of 184 patients. In each group: folic acid 15mg/day versus placebo, orally for at least 3 months (duration of a cycle of spermatogenesis). This assay will evaluate the effectiveness of treatment with folic acid compared to its placebo in infertile men with the outcome of IVF+/-ICSI techniques (pregnancy rate). It will also assess the impact of folate therapy on sperm parameters, and further, the impact on abnormal sperm DNA methylation profiles.

Official Title
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Impact of Folates in the Care of the Male Infertility

Conditions
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Male Infertility

Intervention / Treatment
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* Drug: Folic acid
* Drug: placebo of folic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Couple whose man is from 18 to 60 years old Couple whose man presents an infertility indicating a care in VITRO fertilization with or without intracytoplasmic sperm injection (IVF +/- ICSI) Couple whose spouse is from 18 to 38 years old Couple whose spouse do not present particular factors of infertility Couple Taken care in IVF +/- ICSI Couple with social insurance 2 members of the couple having signed the consent Exclusion Criteria: Etiology of not genetic known male infertility : infertility of neoplastic origine, infertility of definitive obstructive origin Presence of a factor of feminine infertility : A definitive infertility tubal, Turned out ovarian incapacity (FSH > 9 and/or CFA <= 8) Male infertility requiring the appeal to some sperm testicular or in some frozen sperm- Men or women attend of HIV or hepatitis B or C Epileptic men Men under anti-folic treatment Men presenting a big sensibility to the folic acid or to one of the constituents of the drug Couple of which one of the partners refuses to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Folic acid<br>tablets of 5 mg of folic acid | Drug: Folic acid<br>* Taking of folic acid 15 mg per day by hanging oral route during 3 at 4 months<br>|
| Placebo Comparator: Placebo<br>Tablets of placebo of folic acid | Drug: placebo of folic acid<br>* Taking of placebo of folic acid by hanging oral route during 3 at 4 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rates of pregnancy in IVF +/- ICSI and spontaneous pregnancy according to the arm of treatment | Estimate the efficiency of the treatment by folic acid at infertile men on the improvement of improvement of the pregnancy rates in IVF +/- ICSI and spontaneous pregnancy before IVF +/- ICSI | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of improvement of the sperm parameters with acid folic treatment | Estimate the efficiency of the treatment by folic acid on the sperm parameters | 3 months | 
| The rate of improvement of the nuclear quality of gametes with acid folic treatment | Estimate the efficiency of the treatment by folic acid on the nuclear quality of gametes | 3 months | 
| The rate of pregnancy of couple with infertile men treated by folic acid according to the methylene-tetrahydrofolate reductase (MTHFR) genotype | Estimate the impact of the methylene-tetrahydrofolate reductase (MTHFR) genotype of the patients on the rates of pregnancy according to the arm of treatment | 3 months | 
| The difference between the methylene-tetrahydrofolate reductase (MTHFR) genotype of the patients on sperm parameters according to the arm of treatment | Estimate the impact of methylene-tetrahydrofolate reductase (MTHFR) genotype of the patients on sperm parameters according to the arm of treatment | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MTHFR genotype, Male infertility, folic acid, in VITRO fertilization, sperm parameters