Oral Astaxanthin and Semen Quality, Fertilization and Embryo Development in Assisted Reproduction Techniques Procedures

Study Overview
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Brief Summary
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The purpose of the study is to determine whether administration of dietary supplement of astaxanthin with vitamin E improves the quality of sperm, fertilization and embryo development in Assisted Reproduction Techniques (ART) procedures.

Detailed Description
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In the study male patients diagnosed with oligoasthenozoospermia - with an abnormal sperm concentration and motility, irrespective of the morphology of spermatozoa - treated with their female partner with assisted reproduction techniques (ISCI) will be included. In the double blind study male patients will be given astaxanthin with vitamin E (study group, 40 patients) or placebo (control group, 40 patients) for three months prior to ART. In the study and the control group the quality of sperm (spermiogram), DNA fragmentation and mitochondrial membrane potential of semen before and after the dietary supplementation will be evaluated. In the ART procedure (ICSI) the fertilization rate, the quality of embryos, pregnancy rates and miscarriages rates in 1st trimester will be compared between the study and control group.

Official Title
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Effect of Oral Administration of Astaxanthin on Semen Quality, Fertilization and Embryo Development in Assisted Reproduction Techniques Procedures

Conditions
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Infertility, Male

Intervention / Treatment
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* Dietary Supplement: astaxanthin with vitamin E
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: oligoasthenozoospermia with of without teratozoospermia by WHO criteria from the year 2010 fresh semen female partner younger than 38 years idiopathic or tubal infertility in female partners at least 4 oocytes retrieved in previous ovarian punction in ART cycle, if previously performed 1st, 2nd or 3rd cycle of ART Exclusion Criteria: genetic indication for ART procedure donated semen polycystic ovary syndrome in female partner dietary supplementation intake of antioxidants (selenium, zink, vitamin E, vitamin C, vitamin A) in male participant in the last three months smoking in male participant >20 cigarettes per day

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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
Interventional Model Description: Eighty infertile men with OAT were randomly assigned to receive either daily 16 mg of astaxanthin and 40 mg of vitamin E in capsules or placebo. At baseline and after three months of treatment semen quality was assessed according to the WHO guidelines. The sperm concentration, motility and morphology were determined by standard microscopic analyses. Sperm DNA fragmentation was evaluated using a TUNEL assay . Mitochondrial membrane potential was measured by means of 3,3'-dihexyloxacarbocyanine iodide (DiOC6) staining as an indicator of mitochondrial membrane integrity and the mitochondrial potential capacity to generate ATP by oxidative phosphorylation. The serum level of FSH was measured by a solid-phase, two-site chemiluminescent immunometric assay.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: astaxanthin with vitamin E<br>The participants in the study group will be given perorally four tablets of 4 mg astaxanthin with 10 mg vitamin E (Astasan, Sensilab, Slovenia) daily, taken in single daily dose. The total daily dose will be 16 mg astaxanthin with 40 mg vitamin E. The product will be taken for three months continuously. | Dietary Supplement: astaxanthin with vitamin E<br>* Four tablets of 4 mg astaxanthin with 10 mg vitamin E daily, taken at once. Daily dose is 16 mg astaxanthin with 40 mg vitamin E. Continuously for three months.<br>* Other names: Astasan, Sensilab, Slovenia;|
| Placebo Comparator: placebo<br>The participants in the control group will be given perorally four tablets of placebo daily taken in single daily dose. The placebo tablets are of the same size and colour as the study tablets and were produced by manufacturer of Astasan, Sensilab, Slovenia. The placebo will be taken for three months continuously. | Other: Placebo<br>* Four tablets of placebo daily, taken at once. Continuously for three months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| semen quality | In semen quality the spermiogram, DNA fragmentation and mitochondrial membrane potential before and after the intervention will be evaluated. The DNA fragmentation will be evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL) method, and mitochondrial membrane potential with carbocyanine fluorochrome DiOC6. | three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| follicle stimulating hormone (FSH) | FSH levels in before and after the intervention will be evaluated in infertile men with oligoasthenozoospermia. | three months | 
| fertilization and embryo development in Assisted Reproduction Techniques (ART) | Fertilization rates and the quality of embryo development on day 3 in ICSI procedure in infertile couples will be determined after the three months of dietary supplementation of astaxanthin with vitamin E taken by infertile men with oligoasthenozoospermia. | six months | 
| pregnancy rates and miscarriage rates in 1st trimester after ART | Pregnancy rates and miscarriage rates in 1st trimester after ART will be determined after the three months of dietary supplementation of astaxanthin with vitamin E taken by infertile men with oligoasthenozoospermia. | nine months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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apoptosis, male infertility, spermatogenesis, antioxidants, DNA damage, mitochondrial membrane potential