Administration of Antioxidants to Infertile Men and Sperm Quality
Primary Purpose
Male Infertility
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Spermotrend
Sponsored by
About this trial
This is an interventional treatment trial for Male Infertility focused on measuring sperm, infertility, asthenospermia, oligospermia, teratozoospermia, antioxidants
Eligibility Criteria
Inclusion criteria
- Men, 18-50 years old
Infertility defined as follows:
- Failure to obtain a pregnancy after at least twelve (12) months of regular sexual intercourse without the use of contraceptives or six (6) months if the woman is> 35 years old AND
- At least one previous abnormal spermiogram, with at least one pathological parameter (concentration, motility, morphology), according to the WHO 2010 criteria.
- No treatment for infertility in the last three (3) months
- Normal hormone profile (TSH, FSH, LH, total testosterone, prolactin)
- Negative culture for mycoplasma or ureaplasma
- Physiological scrotal ultrasound
Exclusion criteria
- Genetic cause of infertility
- History of cryptorchidism
- History of orchectomy
- History of testicular cancer
- History of severe heart, liver or kidney disease
- History of endocrine disease (primary or secondary hypogonadism, hyperprolactinemia, thyroid, pituitary or adrenal disease)
- History of systemic disease or treatment in the last three (3) months
- BMI > 30 kg/m2
- Participation in another study and the possibility of the patient not being available for follow-up
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Intervention Group
Control Group
Arm Description
Outcomes
Primary Outcome Measures
Sperm parameters
Sperm motility(Sperm motility was classified using a four-category scheme: A:rapid progressive, B:slow progressive, C:non-progressive, and D:immotile , %A+B, normal values >32% A+B)
Sperm parameters
Sperm motility(Sperm motility was classified using a four-category scheme: A:rapid progressive, B:slow progressive, C:non-progressive, and D:immotile , %A+B, normal values >32% A+B)
Sperm parameters
Sperm concentration (ml, normal values > 1.5 ml)
Sperm parameters
Sperm concentration (ml, normal values > 1.5 ml)
Sperm parameters
Sperm vitality (%, normal values > 58%)
Sperm parameters
Sperm vitality (%, normal values > 58%)
Sperm parameters
Sperm morphology(Tygerberg Strict Criteria were used for the evaluation of human sperm morphology, normal form per 100 sperm, normal values >4%)
Sperm parameters
Sperm morphology(Tygerberg Strict Criteria were used for the evaluation of human sperm morphology, normal form per 100 sperm, normal values >4%)
Secondary Outcome Measures
Reactive Oxygen Species (ROS)
ROS (8-hydroxy-2-deoxy-quanosine%, normal values < 3% on sperm)
Reactive Oxygen Species (ROS)
ROS (8-hydroxy-2-deoxy-quanosine%, normal values < 3% on sperm)
DNA fragmentation Index (DFI)
DFI (%DFI: % sperm cells containing damaged DNA)
DNA fragmentation Index (DFI)
DFI (%DFI: % sperm cells containing damaged DNA)
Full Information
NCT ID
NCT04256278
First Posted
December 19, 2019
Last Updated
March 27, 2020
Sponsor
Aristotle University Of Thessaloniki
Collaborators
Andrology lab Zeginiadou, Armatura
1. Study Identification
Unique Protocol Identification Number
NCT04256278
Brief Title
Administration of Antioxidants to Infertile Men and Sperm Quality
Official Title
Does Antioxidant Administration Improve Sperm Quality in Infertile Men
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Unknown status
Study Start Date
March 30, 2020 (Anticipated)
Primary Completion Date
January 30, 2021 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Aristotle University Of Thessaloniki
Collaborators
Andrology lab Zeginiadou, Armatura
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this randomized clinical trial is to assess the effect of oral antioxidant administration to infertile men, by evaluating semen variables, sperm DFI and levels of ROS. Oral antioxidants or placebo will be given for 3 consecutive months.
The study will recruit infertile men, who have one previous abnormal spermiogram, with at least one pathological variable (concentration, motility, morphology), according to WHO 2010 criteria. Participants will be recruited in the outpatient clinic of the Unit of Human Reproduction and of the Unit of Reproductive Endocrinology at the 1st Ob/Gyn Dept.
Detailed Description
Infertility affects up to 15% of couples trying to conceive with the male factor contributing in about 50% of cases. Oxidative stress (OS) has been found as one of the many factors causing male infertility, by inducing sperm damage. OS causes cell damage due to the raised production of reactive oxygen species (ROS), that overcome the antioxidant mechanisms of the human body. ROS are oxidizing agents that are produced as a by-product of oxygen metabolism, having at least one free electron. Due to this free electrone in their outer layer, the form very active or unstable substances. While small amounts of ROS are necessary for the proper function of sperm, increased amounts have a negative effect on sperm quality and can harm its fertility potential, thus inducing male infertility.
Spermatozoa were the first cells found to be sensitive to OS, as they lack the necessary repair cytoplasmic enzyme systems, thus being unable to repair damage. In addition, their cytoplasmic membranes are rich in polyunsaturated fatty acids (PUFAs), making them highly susceptible to oxygen-induced damage, such as lipid peroxidation (LPO). Rapid loss of intracellular adenosine triphosphate (ATP) by LPO, is responsible for axial damage, morphological damage to the sperm neck and reduced sperm motility; these events contribute to reduced sperm motility.
OS has also been associated with reduced fertilization, delayed intrauterine growth, miscarriages, birth defects (including autism) and childhood cancer. ROS found in semen come from a variety of endogenous and exogenous factors. Human sperm includes mature and immature sperm cells, leukocytes, and white blood cells. The leukocytes (mainly neutrophils and macrophages) and the immature spermatozoa are considered the major endogenous sources of ROS, whereas lifestyle, such as smoking, excessive alcohol consumption and other environmental factors such as radiation and toxins may contribute to the production of exogenous ROS.
As oxidative stress (OS) results from the imbalance of ROS overproduction and the reduced capacity of sperm antioxidant systems, many studies have aimed to improve sperm quality by administering antioxidant therapeutic regimens. In general, antioxidant therapy involves the administration of oral antioxidants, and the in vitro addition of antioxidants to culture media that are used for sample preparation in assisted reproduction techniques (ART). Many different antioxidants combinations have been studied. More and more studies have shown the beneficial effect of antioxidants on reducing sperm fragmentation and improving sperm quality. Agarwal & Sekhon's study showed a positive correlation between antioxidant therapy and various semen parameters. However, no firm conclusion regarding the beneficial effect of oral antioxidants can be made, as the majority of available studies had small sample size, used different antioxidant combinations, and the techniques that were used for the detection of ROS and DNA fragmentation index (DFI) were not standardized.
AIM OF THE STUDY The purpose of this randomized clinical trial is to assess the effect of oral antioxidant administration to infertile men, by evaluating semen variables, sperm DFI and levels of ROS.Oral antioxidants or placebo will be given for 3 consecutive months.
This study will take place at the Unit of Reproductive Endocrinology at the 1st Ob/Gyn Dept, Medical School, Aristotle University of Thessaloniki in collaboration with the private andrology diagnostic center of Mr Th. Zeginiadou.
PATIENTS The study will recruit infertile men, who have one previous abnormal spermiogram, with at least one pathological variable (concentration, motility, morphology), according to WHO 2010 criteria.
OUTCOMES
Main Outcome:
WHO Sperm analysis variables: concentration, motility, morphology.
Secondary outcomes:
Concentration of ROS in sperm and sperm DFI
STUDY DESIGN
Type of study:
Randomized clinical trial
The study will recruit infertile men, who have one previous abnormal spermiogram, with at least one pathological variable (concentration, motility, morphology), according to WHO 2010 criteria. Participants will be recruited in the outpatient clinic of the Unit of Human Reproduction and of the Unit of Reproductive Endocrinology at the 1st Ob/Gyn Dept. Selected participants will sign the consent form and will be asked to sample sperm at the private andrology diagnostic center of Mr Th. Zeginiadou. The sperm samples will be evaluated regarding the concentration, motility, morphology and vitality of spermatozoa, as well as the concentration of ROS, and DFI. Oral antioxidants or placebo will be given for 3 consecutive months. At the end of the 3 months period participants will be asked to re-sample their sperm in order to evaluate the same variables.
Sample size calculation Estimated sample size for two-sample means test, assuming and common standard deviation of 15 and a mean motility of 20 in the control group and 30 in the antioxidant group results in calculated sample size of 74. To allow for dropouts 80 patients will be recruited.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Male Infertility
Keywords
sperm, infertility, asthenospermia, oligospermia, teratozoospermia, antioxidants
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
quadruple-blind study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
use of placebo, masked randomization list
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention Group
Arm Type
Experimental
Arm Title
Control Group
Arm Type
Placebo Comparator
Intervention Type
Other
Intervention Name(s)
Spermotrend
Intervention Description
oral administration of antioxidants for three months
Primary Outcome Measure Information:
Title
Sperm parameters
Description
Sperm motility(Sperm motility was classified using a four-category scheme: A:rapid progressive, B:slow progressive, C:non-progressive, and D:immotile , %A+B, normal values >32% A+B)
Time Frame
immediately before treatment initiation
Title
Sperm parameters
Description
Sperm motility(Sperm motility was classified using a four-category scheme: A:rapid progressive, B:slow progressive, C:non-progressive, and D:immotile , %A+B, normal values >32% A+B)
Time Frame
immediately after the end of a 3 month treatment
Title
Sperm parameters
Description
Sperm concentration (ml, normal values > 1.5 ml)
Time Frame
immediately before treatment initiation
Title
Sperm parameters
Description
Sperm concentration (ml, normal values > 1.5 ml)
Time Frame
immediately after the end of a 3 month treatment
Title
Sperm parameters
Description
Sperm vitality (%, normal values > 58%)
Time Frame
immediately before treatment initiation
Title
Sperm parameters
Description
Sperm vitality (%, normal values > 58%)
Time Frame
immediately after the end of a 3 month treatment
Title
Sperm parameters
Description
Sperm morphology(Tygerberg Strict Criteria were used for the evaluation of human sperm morphology, normal form per 100 sperm, normal values >4%)
Time Frame
immediately before treatment initiation
Title
Sperm parameters
Description
Sperm morphology(Tygerberg Strict Criteria were used for the evaluation of human sperm morphology, normal form per 100 sperm, normal values >4%)
Time Frame
immediately after the end of a 3 month treatment
Secondary Outcome Measure Information:
Title
Reactive Oxygen Species (ROS)
Description
ROS (8-hydroxy-2-deoxy-quanosine%, normal values < 3% on sperm)
Time Frame
immediately before treatment initiation
Title
Reactive Oxygen Species (ROS)
Description
ROS (8-hydroxy-2-deoxy-quanosine%, normal values < 3% on sperm)
Time Frame
immediately after the end of a 3 month treatment
Title
DNA fragmentation Index (DFI)
Description
DFI (%DFI: % sperm cells containing damaged DNA)
Time Frame
immediately before treatment initiation
Title
DNA fragmentation Index (DFI)
Description
DFI (%DFI: % sperm cells containing damaged DNA)
Time Frame
immediately after the end of a 3 month treatment
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria
Men, 18-50 years old
Infertility defined as follows:
Failure to obtain a pregnancy after at least twelve (12) months of regular sexual intercourse without the use of contraceptives or six (6) months if the woman is> 35 years old AND
At least one previous abnormal spermiogram, with at least one pathological parameter (concentration, motility, morphology), according to the WHO 2010 criteria.
No treatment for infertility in the last three (3) months
Normal hormone profile (TSH, FSH, LH, total testosterone, prolactin)
Negative culture for mycoplasma or ureaplasma
Physiological scrotal ultrasound
Exclusion criteria
Genetic cause of infertility
History of cryptorchidism
History of orchectomy
History of testicular cancer
History of severe heart, liver or kidney disease
History of endocrine disease (primary or secondary hypogonadism, hyperprolactinemia, thyroid, pituitary or adrenal disease)
History of systemic disease or treatment in the last three (3) months
BMI > 30 kg/m2
Participation in another study and the possibility of the patient not being available for follow-up
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Stratis Kolibianakis, Professor
Phone
2313323374
Email
stratis.kolibianakis@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Pinelopi Ioannidou, MD
Phone
6986707120
Email
pinioannidou@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stratis Kolibianakis, Professor
Organizational Affiliation
Aristotle University Thessaloniki
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
29713542
Citation
Majzoub A, Agarwal A. Systematic review of antioxidant types and doses in male infertility: Benefits on semen parameters, advanced sperm function, assisted reproduction and live-birth rate. Arab J Urol. 2018 Jan 2;16(1):113-124. doi: 10.1016/j.aju.2017.11.013. eCollection 2018 Mar.
Results Reference
result
PubMed Identifier
24872947
Citation
Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. World J Mens Health. 2014 Apr;32(1):1-17. doi: 10.5534/wjmh.2014.32.1.1. Epub 2014 Apr 25.
Results Reference
result
PubMed Identifier
23543240
Citation
Chen SJ, Allam JP, Duan YG, Haidl G. Influence of reactive oxygen species on human sperm functions and fertilizing capacity including therapeutical approaches. Arch Gynecol Obstet. 2013 Jul;288(1):191-9. doi: 10.1007/s00404-013-2801-4. Epub 2013 Mar 30.
Results Reference
result
PubMed Identifier
18281241
Citation
Tremellen K. Oxidative stress and male infertility--a clinical perspective. Hum Reprod Update. 2008 May-Jun;14(3):243-58. doi: 10.1093/humupd/dmn004. Epub 2008 Feb 14.
Results Reference
result
PubMed Identifier
19768529
Citation
Zini A, San Gabriel M, Baazeem A. Antioxidants and sperm DNA damage: a clinical perspective. J Assist Reprod Genet. 2009 Aug;26(8):427-32. doi: 10.1007/s10815-009-9343-5. Epub 2009 Sep 19.
Results Reference
result
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Administration of Antioxidants to Infertile Men and Sperm Quality
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