Clinical trial NCT05421234: Effect of COVID-19 on Platelet Mitochondrial Bioenergetic, Antioxidants and Oxidative Stress in Infertile Men.
Official title: Effect of COVID-19 on Spermiogram, Platelet Mitochondrial Bioenergetic, Antioxidants and Oxidative Stress in Infertile Men
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Infertility, Male
COVID-19
Keywords: men infertility
after-COVID-19
platelets
mitochondrial bioenergetics
coenzyme Q10
oxidative stress
Lead sponsor: Comenius University
Sponsor class: OTHER
Collaborators: name: GYN-FIV
First posted: 2022-06-16
Enrollment: 45
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* disagreement with informed consent

Primary outcomes:
measure: Clinical symptoms
timeFrame: 15 minutes
measure: Damaged platelet mitochondrial bioenergetics 1
timeFrame: 1 day
measure: Damaged platelet mitochondrial bioenergetics 2
timeFrame: 1 day
measure: Damaged platelet mitochondrial bioenergetics 3
timeFrame: 1 day
measure: Damaged platelet mitochondrial bioenergetics 4
timeFrame: 1 day
measure: Damaged platelet mitochondrial bioenergetics 5
timeFrame: 1 day
measure: Damaged platelet mitochondrial bioenergetics 6
timeFrame: 1 day
measure: Endogenous coenzyme Q10-TOTAL 1
timeFrame: 1 day
measure: Endogenous coenzyme Q10-TOTAL 2
timeFrame: 1 day
measure: Endogenous coenzyme Q10-TOTAL 3
timeFrame: 1 day
measure: Endogenous coenzyme TBARS
timeFrame: 1 day
measure: Sperm analysis 1
timeFrame: 1 day
measure: Sperm analysis 2
timeFrame: 1 day
measure: Sperm analysis 3
timeFrame: 1 day
measure: Sperm analysis 4
timeFrame: 1 day
Secondary outcomes:
Other outcomes:
Locations:
city: Bratislava
country: Slovakia
facility: Pharmacobiochemical Laboratory of Third Department of Internal Medicine, Faculty of Medicine Comenius University in Bratislava
Study officials:
affiliation: CU in Bratislava, Faculty of Medicine, Pharmacobiochemical Laboratory of 3rd department of Medicine
name: Anna Gvozdjáková, Prof.Dr.DSc.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sheweita SA, Tilmisany AM, Al-Sawaf H. Mechanisms of male infertility: role of antioxidants. Curr Drug Metab. 2005 Oct;6(5):495-501. doi: 10.2174/138920005774330594.
citation: Gvozdjakova A, Kucharska J, Dubravicky J, Mojto V, Singh RB. Coenzyme Q(1)(0), alpha-tocopherol, and oxidative stress could be important metabolic biomarkers of male infertility. Dis Markers. 2015;2015:827941. doi: 10.1155/2015/827941. Epub 2015 Feb 25.
citation: Gvozdjakova A, Sumbalova Z, Kucharska J, Chladekova A, Rausova Z, Vancova O, Komlosi M, Ulicna O, Mojto V. Platelet mitochondrial bioenergetic analysis in patients with nephropathies and non-communicable diseases: a new method. Bratisl Lek Listy. 2019;120(9):630-635. doi: 10.4149/BLL_2019_104.
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citation: Gvozdjakova A, Sumbalova Z, Kucharska J, Szamosova M, Capova L, Rausova Z, Vancova O, Mojto V, Langsjoen P, Palacka P. Platelet mitochondrial respiration and coenzyme Q10 could be used as new diagnostic strategy for mitochondrial dysfunction in rheumatoid diseases. PLoS One. 2021 Sep 28;16(9):e0256135. doi: 10.1371/journal.pone.0256135. eCollection 2021.
citation: Sumbalova Z, Kucharska J, Palacka P, Rausova Z, Langsjoen PH, Langsjoen AM, Gvozdjakova A. Platelet mitochondrial function and endogenous coenzyme Q10 levels are reduced in patients after COVID-19. Bratisl Lek Listy. 2022;123(1):9-15. doi: 10.4149/BLL_2022_002.
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