Administration of Antioxidants to Infertile Men and Sperm Quality

April 17, 2024 updated by: E.M. Kolibianakis, Aristotle University Of Thessaloniki

Does Antioxidant Administration Improve Sperm Quality in Infertile Men

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 variable: motility.

Secondary outcomes:

WHO Sperm analysis variables: concentration, morphology. 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.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Greece
    • Central Makedonia
      • Thessaloníki, Central Makedonia, Greece, 56403
        • Unit of Assisted Reproduction, 1st Department of Obstetrics-Gynecology -Papageorgiou General Hospital, Thessaloniki, Greece

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 48 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria

  1. Men, 18-50 years old

  2. 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.
  3. No treatment for infertility in the last three (3) months
  4. Normal hormone profile (TSH, FSH, LH, total testosterone, prolactin)
  5. Negative culture for mycoplasma or ureaplasma
  6. Physiological scrotal ultrasound

Exclusion criteria

  1. Genetic cause of infertility
  2. History of cryptorchidism
  3. History of orchectomy
  4. History of testicular cancer
  5. History of severe heart, liver or kidney disease
  6. History of endocrine disease (primary or secondary hypogonadism, hyperprolactinemia, thyroid, pituitary or adrenal disease)
  7. History of systemic disease or treatment in the last three (3) months
  8. BMI > 30 kg/m2
  9. Participation in another study and the possibility of the patient not being available for follow-up

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention Group
Other: Spermotrend
oral administration of antioxidants for three months
Placebo Comparator: Control Group
Other: Spermotrend
oral administration of antioxidants for three months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sperm parameters
Time Frame: immediately before treatment initiation
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)
immediately before treatment initiation
Sperm parameters
Time Frame: immediately after the end of a 3 month treatment
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)
immediately after the end of a 3 month treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sperm parameters
Time Frame: immediately before treatment initiation
Sperm concentration (ml, normal values > 1.5 ml)
immediately before treatment initiation
Sperm parameters
Time Frame: immediately after the end of a 3 month treatment
Sperm concentration (ml, normal values > 1.5 ml)
immediately after the end of a 3 month treatment
Sperm parameters
Time Frame: immediately before treatment initiation
Sperm morphology(Tygerberg Strict Criteria were used for the evaluation of human sperm morphology, normal form per 100 sperm, normal values >4%)
immediately before treatment initiation
Sperm parameters
Time Frame: immediately after the end of a 3 month treatment
Sperm morphology(Tygerberg Strict Criteria were used for the evaluation of human sperm morphology, normal form per 100 sperm, normal values >4%)
immediately after the end of a 3 month treatment
Reactive Oxygen Species (ROS)
Time Frame: immediately before treatment initiation
ROS (8-hydroxy-2-deoxy-quanosine%, normal values < 3% on sperm)
immediately before treatment initiation
Reactive Oxygen Species (ROS)
Time Frame: immediately after the end of a 3 month treatment
ROS (8-hydroxy-2-deoxy-quanosine%, normal values < 3% on sperm)
immediately after the end of a 3 month treatment
DNA fragmentation Index (DFI)
Time Frame: immediately before treatment initiation
DFI (%DFI: % sperm cells containing damaged DNA)
immediately before treatment initiation
DNA fragmentation Index (DFI)
Time Frame: immediately after the end of a 3 month treatment
DFI (%DFI: % sperm cells containing damaged DNA)
immediately after the end of a 3 month treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aristotle University Of Thessaloniki

Collaborators

Andrology lab Zeginiadou
Armatura

Investigators

  • Principal Investigator: Stratis Kolibianakis, Professor, Aristotle University Thessaloniki

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 28, 2020

Primary Completion (Actual)

April 29, 2022

Study Completion (Actual)

April 29, 2022

Study Registration Dates

First Submitted

December 19, 2019

First Submitted That Met QC Criteria

February 3, 2020

First Posted (Actual)

February 5, 2020

Study Record Updates

Last Update Posted (Actual)

April 19, 2024

Last Update Submitted That Met QC Criteria

April 17, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UHR-15

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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