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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Folic acid | Experimental | tablets of 5 mg of folic acid |
|
| Placebo | Placebo Comparator | Tablets of placebo of folic acid |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Folic acid | Drug | Taking of folic acid 15 mg per day by hanging oral route during 3 at 4 months |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Emmanuelle MATHIEU - D'ARGENT, MD | TENON Hospital - APHP | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Service of gynaecology-obstetrics and medicine of the reproduction, Tenon Hospital - APHP | Paris | 75020 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8405528 | Background | Bentivoglio G, Melica F, Cristoforoni P. Folinic acid in the treatment of human male infertility. Fertil Steril. 1993 Oct;60(4):698-701. doi: 10.1016/s0015-0282(16)56225-6. | |
| 11302150 | Background | Bezold G, Lange M, Peter RU. Homozygous methylenetetrahydrofolate reductase C677T mutation and male infertility. N Engl J Med. 2001 Apr 12;344(15):1172-3. doi: 10.1056/NEJM200104123441517. No abstract available. |
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| ID | Term |
|---|---|
| D007248 | Infertility, Male |
| ID | Term |
|---|---|
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007246 | Infertility |
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Not provided
| ID | Term |
|---|---|
| D005492 | Folic Acid |
| ID | Term |
|---|---|
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| placebo of folic acid | Drug | Taking of placebo of folic acid by hanging oral route during 3 at 4 months |
|
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 |
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| 11872201 | Background | Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA, Steegers-Theunissen RP. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2002 Mar;77(3):491-8. doi: 10.1016/s0015-0282(01)03229-0. |
| 35506389 | Derived | de Ligny W, Smits RM, Mackenzie-Proctor R, Jordan V, Fleischer K, de Bruin JP, Showell MG. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2022 May 4;5(5):CD007411. doi: 10.1002/14651858.CD007411.pub5. |
| D052801 |
| Male Urogenital Diseases |
| D006571 | Heterocyclic Compounds |