Astax-ART: Oral Astaxanthin and Semen Quality, Fertilization and Embryo Development in Assisted Reproduction Techniques Procedures

Sponsor

University Medical Centre Ljubljana (Other)

Overall Status

Completed

CT.gov ID

NCT02310087

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Infertility, Male	Dietary Supplement: astaxanthin with vitamin E Other: Placebo	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Participant, Care Provider, Investigator)

Masking Description:

no other masking

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 1, 2014

Actual Primary Completion Date :

Jan 1, 2019

Actual Study Completion Date :

Jan 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: astaxanthin with vitamin E 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 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. Other Names: Astasan, Sensilab, Slovenia
Placebo Comparator: placebo 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 Four tablets of placebo daily, taken at once. Continuously for three months.

Arm

Intervention/Treatment

Active Comparator: astaxanthin with vitamin E

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

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.

Other Names:

Astasan, Sensilab, Slovenia

Placebo Comparator: placebo

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

Four tablets of placebo daily, taken at once. Continuously for three months.

Outcome Measures

Primary Outcome Measures

semen quality [three months]
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.

Secondary Outcome Measures

follicle stimulating hormone (FSH) [three months]
FSH levels in before and after the intervention will be evaluated in infertile men with oligoasthenozoospermia.
fertilization and embryo development in Assisted Reproduction Techniques (ART) [six months]
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.
pregnancy rates and miscarriage rates in 1st trimester after ART [nine months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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