Clinical trial NCT02310087: Oral Astaxanthin and Semen Quality, Fertilization and Embryo Development in Assisted Reproduction Techniques Procedures
Official title: Effect of Oral Administration of Astaxanthin on Semen Quality, Fertilization and Embryo Development in Assisted Reproduction Techniques Procedures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility, Male
Keywords: male infertility
spermatogenesis
antioxidants
DNA damage
mitochondrial membrane potential
apoptosis
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2014-12-05
Enrollment: 80
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: semen quality
timeFrame: three months
Secondary outcomes:
measure: follicle stimulating hormone (FSH)
timeFrame: three months
measure: fertilization and embryo development in Assisted Reproduction Techniques (ART)
timeFrame: six months
measure: pregnancy rates and miscarriage rates in 1st trimester after ART
timeFrame: nine months
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: Division of Ob/Gyn, University Medical Centre Ljubljana
Study officials:
affiliation: Division of Ob/Gyn, University Medical Centre Ljubljana, Slovenia
name: Bojana Pinter, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Yuan 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.
citation: Agarwal 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.
citation: Higuera-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.
citation: Comhaire 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.
citation: Franco 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.
citation: Chemes 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.
citation: Virro 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.
citation: Marchetti 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.