Effect of COVID-19 on Platelet Mitochondrial Bioenergetic, Antioxidants and Oxidative Stress in Infertile Men. (COVInfertility)

June 16, 2022 updated by: Comenius University

Effect of COVID-19 on Spermiogram, Platelet Mitochondrial Bioenergetic, Antioxidants and Oxidative Stress in Infertile Men

To verify the hypothesis that infertility and the effect of SARS-CoV-2 on infertility may damage platelet mitochondrial bioenergetics and endogenous coenzyme Q10 levels in infertile men.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Infertility is defined as the failure of the reproductive system to achieve pregnancy after 12 months of unprotected sex life. The pathobiochemical mechanisms of male fertility disorders include reduced sperm motility and quality, oxidative stress, reduced antioxidant capacity, mtDNA fragmentation, and sperm mitochondrial dysfunction.

Sperm contain a number of mitochondria that are spirally arranged around the middle part of the axomen. The main role of mitochondria in spermatozoa is to generate the energy needed for their motility (1, 2). Endogenous sources - coenzyme Q10 and carnitine - are key for energy production (ATP) in sperm mitochondria. Physiological functions of sperm require a minimal amount of reactive oxygen species (ROS), but uncontrolled ROS production contributes to reduced motility and sperm count, fragmentation of mtDNA (3).

In recent years, blood cells (platelets, lymphocytes and monocytes) have been used to diagnose mitochondrial disorders. Isolated peripheral blood platelets are an available source of mitochondria to assess mitochondrial health. Platelets receive energy mainly through glycolysis and oxidative phosphorylation. Platelet mitochondrial dysfunction has been demonstrated in patients with chronic kidney disease (4, 5), in patients with rheumatoid arthritis (6), in patients with acute COVID-19 (7). An O2k-respirometer (Oroboros, Austria) (8, 9) is used for respirometric analysis of platelet mitochondrial bioenergetics.

None information is available on the effect of infertility on platelet mitochondrial function, none on the effect of SARS-CoV-2 on platelet mitochondrial function in infertile patients, or the effect of vaccination on sperm function. Testicular damage and subsequent infertility due to SARS-CoV infection is expected. -2, directly via SARS-CoV-2 binding to ACE2 receptors or secondarily, in relation to the immunological and inflammatory response (10). SARS-CoV-2 virus induces excessive production of pro-inflammatory cytokines, mainly interleukin 6 (IL6), interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα). Cytokines can impair sperm movement and reduce sperm count. High levels of pro-inflammatory cytokines have been found in infertile men (with oligozoospermia, asthenozoospermia, teratozoospermia) (11).

SARS-CoV-2 virus can manipulate mitochondrial function in patients with post-COVID-19 syndrome, which may persist for a long time (12). In previous our study the investigators found modulation of platelet mitochondrial respiration, reduction ATP production via oxidative phosphorylation, reduces endogenous coenzyme Q10 production, reprogramming of cellular metabolism patients after 4-7 weeks overcoming acute COVID-19, SARS-CoV-2 (7). In another studies the investigators confirmed platelet mitochondrial bioenergetic deficiency, reduced endogenous coenzyme Q10 production in patients with post-COVID-19 syndrome, 3-6 months after overcoming COVID-19 (13, 14, 15). Results of this study contribute to the understanding of the pathobiochemical mechanisms of infertility on subcellular level and to verify the hypothesis that infertility and the effect of SARS-CoV-2 on infertility may affect platelet mitochondrial bioenergetics and endogenous coenzyme Q10 levels.

Study Type

Interventional

Enrollment (Actual)

45

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 Locations

  • Slovakia
      • Bratislava, Slovakia, 81108
        • Pharmacobiochemical Laboratory of Third Department of Internal Medicine, Faculty of Medicine Comenius University in Bratislava

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

18 years to 40 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Infertile patients without COVID-19
  • Infertile patients after COVID-19 Control group: healthy volunteers

Exclusion Criteria:

  • disagreement with informed consent

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: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: infertile men with post-COVID-19 (vaccinated or without vaccination)
15 infertile men with post-COVID-19 (vaccinated or without vaccination)
Other: diagnostic test and sperm analysis

Diagnostic Test: 2x14 ml of peripheral blood collected in the tube with anticoagulant, for platelet isolation, respirometry mitochondrial analysis, antioxidants (coenzyme Q10, vitamin E, gamma-tocopherol, beta-carotene) and TBARS estimation.

Sperm analysis: standard spermiogram examination (volume, pH, number, motility and pathology) in the broker chamber, as well as extended examinations: mioxsys for redox potential, Vitalsperm (eosin-nigrosine staining) for sperm vitality and anti-sperm antibody (IgG) test.
ACTIVE_COMPARATOR: infertile men without post-COVID-19 (vaccinated or without vaccination)
15 infertile men without post-COVID-19 (vaccinated or without vaccination)
Other: diagnostic test and sperm analysis

Diagnostic Test: 2x14 ml of peripheral blood collected in the tube with anticoagulant, for platelet isolation, respirometry mitochondrial analysis, antioxidants (coenzyme Q10, vitamin E, gamma-tocopherol, beta-carotene) and TBARS estimation.

Sperm analysis: standard spermiogram examination (volume, pH, number, motility and pathology) in the broker chamber, as well as extended examinations: mioxsys for redox potential, Vitalsperm (eosin-nigrosine staining) for sperm vitality and anti-sperm antibody (IgG) test.
ACTIVE_COMPARATOR: Control: 15 healthy men volunteers (no COVID-19, no other pathologies)
15 healthy men volunteers (no COVID-19, no other pathologies) as control group
Other: diagnostic test and sperm analysis

Diagnostic Test: 2x14 ml of peripheral blood collected in the tube with anticoagulant, for platelet isolation, respirometry mitochondrial analysis, antioxidants (coenzyme Q10, vitamin E, gamma-tocopherol, beta-carotene) and TBARS estimation.

Sperm analysis: standard spermiogram examination (volume, pH, number, motility and pathology) in the broker chamber, as well as extended examinations: mioxsys for redox potential, Vitalsperm (eosin-nigrosine staining) for sperm vitality and anti-sperm antibody (IgG) test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical symptoms
Time Frame: 15 minutes
Clinical symptoms: infertile patients without COVID-19 (vaccinated, or none vaccinated) Clinical symptoms patients after COVID-19
15 minutes
Damaged platelet mitochondrial bioenergetics 1
Time Frame: 1 day
Basal oxygen consumption rate in intact platelets (ce)
1 day
Damaged platelet mitochondrial bioenergetics 2
Time Frame: 1 day
rate of mitochondria LEAK respiration with CI-linked substrates (1PM - state 4)
1 day
Damaged platelet mitochondrial bioenergetics 3
Time Frame: 1 day
CI-linked respiration coupled with ATPproduction (2D-CI-linked oxidative phosphorylation capacity), respiration after addition of cytochrome c (2C).
1 day
Damaged platelet mitochondrial bioenergetics 4
Time Frame: 1 day
Maximal oxidative capacity (the electron transfer capacity -ET), after uncoupler titration (3U).
1 day
Damaged platelet mitochondrial bioenergetics 5
Time Frame: 1 day
After addition of exogenous substrate glutamate (4G) non-coupled mitochondrial oxygen consumption.
1 day
Damaged platelet mitochondrial bioenergetics 6
Time Frame: 1 day
Non-coupled oxygen consumption with CI&CII-linked substrate (5S) improvement of mitochondrial parameters representing OXPHOS- and electron tranport capacity (ET-capacity).
1 day
Endogenous coenzyme Q10-TOTAL 1
Time Frame: 1 day
CoQ10-TOTAL in: Platelets (pmol.10-9 cells)
1 day
Endogenous coenzyme Q10-TOTAL 2
Time Frame: 1 day
CoQ10-TOTAL in: Blood (µmol.L-1)
1 day
Endogenous coenzyme Q10-TOTAL 3
Time Frame: 1 day
CoQ10-TOTAL in: Plasma (µmol.L-1)
1 day
Endogenous coenzyme TBARS
Time Frame: 1 day
Endogenous concentration of CoQ10-TOTAL (ubiquinone + ubiquinol) in platelets, blood and plasma CoQ10-TOTAL in: TBARS in plasma (µmol.L-1).
1 day
Sperm analysis 1
Time Frame: 1 day
standard spermiogram examination (volume, pH, number, motility and pathology) in the broker chamber
1 day
Sperm analysis 2
Time Frame: 1 day
mioxsys for redox potential
1 day
Sperm analysis 3
Time Frame: 1 day
Vitalsperm (eosin-nigrosine staining) for sperm vitality
1 day
Sperm analysis 4
Time Frame: 1 day
anti-sperm antibody (IgG) test
1 day

Collaborators and Investigators

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

Sponsor

Comenius University

Collaborators

GYN-FIV

Investigators

  • Principal Investigator: Anna Gvozdjáková, Prof.Dr.DSc., CU in Bratislava, Faculty of Medicine, Pharmacobiochemical Laboratory of 3rd department of Medicine

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)

April 1, 2022

Primary Completion (ANTICIPATED)

December 31, 2022

Study Completion (ANTICIPATED)

March 30, 2023

Study Registration Dates

First Submitted

June 15, 2022

First Submitted That Met QC Criteria

June 15, 2022

First Posted (ACTUAL)

June 16, 2022

Study Record Updates

Last Update Posted (ACTUAL)

June 22, 2022

Last Update Submitted That Met QC Criteria

June 16, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COVID-19-INFERTILITY-SK01/2022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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