Infertility, MaleAstax-ARTNCT02310087
Oral Astaxanthin and Semen Quality, Fertilization and Embryo Development in Assisted Reproduction Techniques Procedures
A study testing astaxanthin with vitamin E in people with Infertility, Male, run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Infertility, Male
- What is being tested?
- astaxanthin with vitamin E
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteSlovenia
- Study dates
- Nov 2014to Jan 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Slovenia1 site
Division of Ob/Gyn, University Medical Centre Ljubljana
Ljubljana, 1000
About this study
Official title: Effect of Oral Administration of Astaxanthin on Semen Quality, Fertilization and Embryo Development in Assisted Reproduction Techniques Procedures
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.
Read the 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.
- Conditions
- Infertility, Male
- Being tested
- astaxanthin with vitamin E, Placebo
- Keywords
- male infertility, spermatogenesis, antioxidants, DNA damage, mitochondrial membrane potential, apoptosis
- Medical subject headings
- Infertility, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
astaxanthin with vitamin EDietary supplement
Also called Astasan, Sensilab, Slovenia
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.
PlaceboOther
Four tablets of placebo daily, taken at once. Continuously for three months.
| Study group | Role | What they receive |
|---|---|---|
| astaxanthin with vitamin E | Active comparator | 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. Receives: Dietary Supplement: astaxanthin with vitamin E |
| placebo | Placebo comparator | 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: three months
Secondary outcomes (3)
follicle stimulating hormone (FSH)
FSH levels in before and after the intervention will be evaluated in infertile men with oligoasthenozoospermia.
Measured: 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.
Measured: 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.
Measured: nine months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2014 (estimated)
- Study startNov 2014
- Primary completionJan 2019
- Study completionJan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Infertility, MaleStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bojana Pinter, University Medical Centre Ljubljana
- Investigators
- Bojana Pinter, MD, PhD, Principal investigator, Division of Ob/Gyn, University Medical Centre Ljubljana, Slovenia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02310087
- Sponsor's protocol ID
- UMCLjubljana-20140041
- Acronym
- Astax-ART
- Status last verified
- Mar 2019
- First submitted
- 3 Dec 2014
- Last updated
- 29 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: The datasets generated and analysed during the current study could not be publicly available because they are in the Slovene language. Unauthorised translation may lead to data misunderstanding or misinterpretation.
Publications
Imamovic Kumalic S, Pinter B. Review of clinical trials on effects of oral antioxidants on basic semen and other parameters in idiopathic oligoasthenoteratozoospermia. Biomed Res Int. 2014;2014:426951. doi: 10.1155/2014/426951. Epub 2014 Mar 31.
PubMed 24800224Yuan JP, Peng J, Yin K, Wang JH. Potential health-promoting effects of astaxanthin: a high-value carotenoid mostly from microalgae. Mol Nutr Food Res. 2011 Jan;55(1):150-65. doi: 10.1002/mnfr.201000414. Epub 2010 Nov 18.
PubMed 21207519Agarwal A, Nallella KP, Allamaneni SS, Said TM. Role of antioxidants in treatment of male infertility: an overview of the literature. Reprod Biomed Online. 2004 Jun;8(6):616-27. doi: 10.1016/s1472-6483(10)61641-0.
PubMed 15169573Higuera-Ciapara I, Felix-Valenzuela L, Goycoolea FM. Astaxanthin: a review of its chemistry and applications. Crit Rev Food Sci Nutr. 2006;46(2):185-96. doi: 10.1080/10408690590957188.
PubMed 16431409Comhaire FH, El Garem Y, Mahmoud A, Eertmans F, Schoonjans F. Combined conventional/antioxidant "Astaxanthin" treatment for male infertility: a double blind, randomized trial. Asian J Androl. 2005 Sep;7(3):257-62. doi: 10.1111/j.1745-7262.2005.00047.x.
PubMed 16110353Franco JG Jr, Baruffi RL, Mauri AL, Petersen CG, Oliveira JB, Vagnini L. Significance of large nuclear vacuoles in human spermatozoa: implications for ICSI. Reprod Biomed Online. 2008 Jul;17(1):42-5. doi: 10.1016/s1472-6483(10)60291-x.
PubMed 18616888Chemes EH, Rawe YV. Sperm pathology: a step beyond descriptive morphology. Origin, characterization and fertility potential of abnormal sperm phenotypes in infertile men. Hum Reprod Update. 2003 Sep-Oct;9(5):405-28. doi: 10.1093/humupd/dmg034.
PubMed 14640375Virro MR, Larson-Cook KL, Evenson DP. Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles. Fertil Steril. 2004 May;81(5):1289-95. doi: 10.1016/j.fertnstert.2003.09.063.
PubMed 15136092Marchetti C, Obert G, Deffosez A, Formstecher P, Marchetti P. Study of mitochondrial membrane potential, reactive oxygen species, DNA fragmentation and cell viability by flow cytometry in human sperm. Hum Reprod. 2002 May;17(5):1257-65. doi: 10.1093/humrep/17.5.1257.
PubMed 11980749
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Oral Administration of Astaxanthin on Semen Quality, Fertilization and Embryo Development in Assisted Reproduction Techniques Procedures
- ClinicalTrials.gov ID
- NCT02310087
- Acronym / sponsor ID
- Astax-ART / UMCLjubljana-20140041
- Conditions
- Infertility, Male
- Keywords
- male infertility, spermatogenesis, antioxidants, DNA damage, mitochondrial membrane potential, apoptosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Study start
- Nov 2014 (actual)
- Primary completion
- Jan 2019 (actual)
- Study completion
- Jan 2019 (actual)
- First posted
- 5 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| astaxanthin with vitamin E | Active comparator | Dietary Supplement: astaxanthin with vitamin EThe 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. |
| placebo | Placebo comparator | Other: PlaceboThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| astaxanthin with vitamin EAlso: Astasan, Sensilab, SloveniaFour 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. | Dietary supplement | astaxanthin with vitamin E |
| PlaceboFour tablets of placebo daily, taken at once. Continuously for three months. | Other | placebo |
Primary outcome
semen quality
Time frame: 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.
3 secondary outcomes
follicle stimulating hormone (FSH)
Time frame: three months
fertilization and embryo development in Assisted Reproduction Techniques (ART)
Time frame: six months
pregnancy rates and miscarriage rates in 1st trimester after ART
Time frame: nine months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2019.
- Background: PubMed 24800224Imamovic Kumalic S, Pinter B. Review of clinical trials on effects of oral antioxidants on basic semen and other parameters in idiopathic oligoasthenoteratozoospermia. Biomed Res Int. 2014;2014:426951. doi: 10.1155/2014/426951. Epub 2014 Mar 31.
- Background: PubMed 21207519Yuan JP, Peng J, Yin K, Wang JH. Potential health-promoting effects of astaxanthin: a high-value carotenoid mostly from microalgae. Mol Nutr Food Res. 2011 Jan;55(1):150-65. doi: 10.1002/mnfr.201000414. Epub 2010 Nov 18.
- Background: PubMed 15169573Agarwal A, Nallella KP, Allamaneni SS, Said TM. Role of antioxidants in treatment of male infertility: an overview of the literature. Reprod Biomed Online. 2004 Jun;8(6):616-27. doi: 10.1016/s1472-6483(10)61641-0.
- Background: PubMed 16431409Higuera-Ciapara I, Felix-Valenzuela L, Goycoolea FM. Astaxanthin: a review of its chemistry and applications. Crit Rev Food Sci Nutr. 2006;46(2):185-96. doi: 10.1080/10408690590957188.
- Background: PubMed 16110353Comhaire FH, El Garem Y, Mahmoud A, Eertmans F, Schoonjans F. Combined conventional/antioxidant "Astaxanthin" treatment for male infertility: a double blind, randomized trial. Asian J Androl. 2005 Sep;7(3):257-62. doi: 10.1111/j.1745-7262.2005.00047.x.
- Background: PubMed 18616888Franco JG Jr, Baruffi RL, Mauri AL, Petersen CG, Oliveira JB, Vagnini L. Significance of large nuclear vacuoles in human spermatozoa: implications for ICSI. Reprod Biomed Online. 2008 Jul;17(1):42-5. doi: 10.1016/s1472-6483(10)60291-x.
- Background: PubMed 14640375Chemes EH, Rawe YV. Sperm pathology: a step beyond descriptive morphology. Origin, characterization and fertility potential of abnormal sperm phenotypes in infertile men. Hum Reprod Update. 2003 Sep-Oct;9(5):405-28. doi: 10.1093/humupd/dmg034.
- Background: PubMed 15136092Virro MR, Larson-Cook KL, Evenson DP. Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles. Fertil Steril. 2004 May;81(5):1289-95. doi: 10.1016/j.fertnstert.2003.09.063.
- Background: PubMed 11980749Marchetti C, Obert G, Deffosez A, Formstecher P, Marchetti P. Study of mitochondrial membrane potential, reactive oxygen species, DNA fragmentation and cell viability by flow cytometry in human sperm. Hum Reprod. 2002 May;17(5):1257-65. doi: 10.1093/humrep/17.5.1257.
- Individual participant dataSharing planned: No. The datasets generated and analysed during the current study could not be publicly available because they are in the Slovene language. Unauthorised translation may lead to data misunderstanding or misinterpretation.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bojana Pinter, MD, PhD principal investigator
Division of Ob/Gyn, University Medical Centre Ljubljana, Slovenia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing astaxanthin with vitamin E in people with Infertility, Male, run by University Medical Centre Ljubljana at 1 site in Slovenia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
semen quality (time frame: three months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02310087, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2019.