COVID 19SEM-COV-19NCT06703723
Impact of Cryopreservation Methods on Post-Thaw SARS-CoV-2 in Semen Samples
An observational study of COVID 19, run by Istituto Clinico Humanitas at 1 site in Italy.
Trial summary
Cryopreservation of seminal fluid or spermatozoa from epididymary and testicular retrieval represents a crucial tool in managing conditions of permanent or temporary infertility, as well as in cases of secretory and excretory azoospermia. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- COVID 19
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- 14 Jan 2021to 16 Apr 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Study population: To analyze the effect of the two cryopreservation methods (slow freezing in two stages and vitrification) on semen samples, we propose to include 20 patients who have been exposed to SARS-CoV-2 infection and 20 control subjects.
Who may be able to join
- Patient population inclusion criteria:
- • Male subjects, aged 18-50 requiring a semen fluid evaluation.
- Positive IgG serological test result performed not more than 3 months before recruitment
- Signed informed consent
- Anamnestic test compilation
- Control subject inclusion criteria:
Show all 10Show fewer
- Male subjects, aged 18-50 requiring a semen fluid evaluation.
- Negative IgG serological test result performed within the last month
- Signed informed consent
- Anamnestic test compilation
Who cannot join
- Patient population exclusion criteria:
- Severe male Factor (azoospermia and <200,00 sperm per ejaculate)
- Fever (>38.5 C) in the 60 days before enrollment
- Treated with antibiotic at the time of enrolment or two months before enrolment
- Treated with cortisone at the time of enrolment or two months before enrolment
- Control subject population exclusion criteria:
Show all 11Show fewer
- Severe male Factor (azoospermia and <200,00 sperm per ejaculate)
- Fever (>38.5 C) in the 60 days before enrolment
- Known history of SARS-CoV-2 infection
- Treated with antibiotic at the time of enrolment or two months before enrolment
- Treated with cortisone at the time of enrolment or two months before enrolment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Cryopreservation on SARS-CoV-2 Semen Samples: Influence of Two Different Cryopreservation Procedures Evaluated After Thawing
Cryopreservation of seminal fluid or spermatozoa from epididymary and testicular retrieval represents a crucial tool in managing conditions of permanent or temporary infertility, as well as in cases of secretory and excretory azoospermia. These pathologies often affect young men and children, making it essential to maintain fertility through cryopreservation methods such as vitrification or two-step cryopreservation of human semen.
The burden of the SARS-CoV-2 virus has rapidly evolved. SARS-CoV-2 causes respiratory, cardiovascular, digestive, and urinary infections, yet no studies have explored its effects on the reproductive system. Recent findings confirm the expression of the virus receptor (ACE2) on certain testicular cells, including Sertoli cells, Leydig cells, and spermatogonia, which could significantly impact fertility and cryopreservation practices.
This study aims to utilize semen samples from individuals exposed to SARS-CoV-2 infection to perform two different cryopreservation procedures, evaluating virus behavior and effects. The objective is to determine whether it is safer to cryopreserve the entire volume of the sample or perform gradient separation to isolate the virus from spermatozoa, potentially establishing a new cryopreservation protocol specific to SARS-CoV-2.
Read the detailed description
The pandemic caused by SARS-CoV-2 ranks among the most devastating events in recent history. Limited knowledge exists regarding the characteristics and behavior of this beta coronavirus, particularly its potential impact on reproductive medicine. Questions remain about the presence of the virus in seminal fluid and whether male semen could serve as a transmission route. Additionally, concerns exist about the virus impairing male reproductive potential through fever or the "cytokine storm" triggered by the immune response.
No current evidence confirms whether SARS-CoV-2 can survive semen cryopreservation, though other viruses, such as influenza, have demonstrated survival in liquid nitrogen freezing. Semen cryopreservation is a critical fertility preservation strategy for conditions like cancers, autoimmune diseases, or cryptorchidism. The contamination of cryopreserved semen by SARS-CoV-2 could turn such samples into hazardous viral reservoirs.
The study aims to investigate the presence of the virus in semen, identify cells expressing viral receptors ACE2 and TMPRSS2, and evaluate the virus's direct and indirect effects on male reproductive capacity. Objectives include determining if SARS-CoV-2 survives cryopreservation procedures and identifying optimal methods to ensure virus-free cryopreserved semen while separating infected material from male gametes.
The study will recruit 20 men exposed to SARS-CoV-2 and 20 control subjects, all treated at the Humanitas Fertility Center, Department of Gynecology, at the Humanitas Research Hospital. Each participant will provide a semen sample for evaluation. This observational study will not involve clinical interventions or alter regular diagnostic procedures.
Participants undergoing routine tests for medically assisted reproduction and deemed eligible after completing an anamnesis questionnaire will be included. Samples will be processed in the Mucosal Immunology and Microbiota Unit at the Humanitas Clinical Institute.
Using cell biology, molecular biology, and flow cytometry techniques, the study will assess viral contamination, receptor expression in spermatozoa, and inflammatory cytokine levels in seminal fluid after two cryopreservation methods: slow two-step freezing and vitrification. Analyses will cover unprocessed semen and samples exposed in vitro to SARS-CoV-2 under BSL3 conditions.
Additionally, the cellular fraction of semen, including granulocytes, lymphocytes, round cells, and spermatozoa, will undergo phenotype and activation state characterization. The study will evaluate viral contamination in cryopreserved semen and assess the effectiveness of protocols designed to separate infected material from male gametes.
- Conditions
- COVID 19
- Keywords
- sars-cov-2, semen cryopreservation, male reproductive health, viral contamination, inflammation
- Medical subject headings
- COVID-19, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Male subjects, aged 18-50 requiring a semen fluid evaluation. • Positive IgG serological test result | Not described | |
| Healthy | Healthy |
What is being measured
The primary outcome is the main question the study is designed to answer.
nvestigation of ACE2 and TMPRSS2 mRNA Expression on Spermatozoa in SARS-CoV-2 Infected Semen Samples
investigate the presence of the mRNA encoding ACE2 and TMPRSS2 on spermatozoa of SARS-CoV-2 semen samples
Measured: through study completion, an average of 1 year
Secondary outcomes (3)
Impact of Cryopreservation Methods on the Presence of Viral RNA in SARS-CoV-2 Infected Semen: A Comparison of Two-Step Cryogenic Freezing and Vitrification
The primary outcome of the study will be to investigate the presence of viral RNA in semen samples after cryopreservation using two-step cryogenic freezing and vitrification methods.
Measured: through study completion, an average of 1 year
valuation of the Presence of the SARS-CoV-2 Viral Genome in Semen Samples"
evaluating the presence of the viral genome
Measured: through study completion, an average of 1 year
Immune profiling
Immune activation compared to controls
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2024
- Study start14 Jan 2021
- Primary completion16 Apr 2021
- Study completion16 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID 19Studies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06703723
- Sponsor's protocol ID
- 230879
- Acronym
- SEM-COV-19
- Status last verified
- Nov 2024
- First submitted
- 19 Nov 2024
- Last updated
- 25 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Cryopreservation on SARS-CoV-2 Semen Samples: Influence of Two Different Cryopreservation Procedures Evaluated After Thawing
- ClinicalTrials.gov ID
- NCT06703723
- Acronym / sponsor ID
- SEM-COV-19 / 230879
- Conditions
- COVID 19
- Keywords
- sars-cov-2, semen cryopreservation, male reproductive health, viral contamination, inflammation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Study start
- 14 Jan 2021 (actual)
- Primary completion
- 16 Apr 2021 (actual)
- Study completion
- 16 Apr 2021 (actual)
- First posted
- 25 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cryopreservation of seminal fluid or spermatozoa from epididymary and testicular retrieval represents a crucial tool in managing conditions of permanent or temporary infertility, as well as in cases of secretory and excretory azoospermia. These pathologies often affect young men and children, making it essential to maintain fertility through cryopreservation methods such as vitrification or two-step cryopreservation of human semen.
The burden of the SARS-CoV-2 virus has rapidly evolved. SARS-CoV-2 causes respiratory, cardiovascular, digestive, and urinary infections, yet no studies have explored its effects on the reproductive system. Recent findings confirm the expression of the virus receptor (ACE2) on certain testicular cells, including Sertoli cells, Leydig cells, and spermatogonia, which could significantly impact fertility and cryopreservation practices.
This study aims to utilize semen samples from individuals exposed to SARS-CoV-2 infection to perform two different cryopreservation procedures, evaluating virus behavior and effects. The objective is to determine whether it is safer to cryopreserve the entire volume of the sample or perform gradient separation to isolate the virus from spermatozoa, potentially establishing a new cryopreservation protocol specific to SARS-CoV-2.
Detailed description
The pandemic caused by SARS-CoV-2 ranks among the most devastating events in recent history. Limited knowledge exists regarding the characteristics and behavior of this beta coronavirus, particularly its potential impact on reproductive medicine. Questions remain about the presence of the virus in seminal fluid and whether male semen could serve as a transmission route. Additionally, concerns exist about the virus impairing male reproductive potential through fever or the "cytokine storm" triggered by the immune response.
No current evidence confirms whether SARS-CoV-2 can survive semen cryopreservation, though other viruses, such as influenza, have demonstrated survival in liquid nitrogen freezing. Semen cryopreservation is a critical fertility preservation strategy for conditions like cancers, autoimmune diseases, or cryptorchidism. The contamination of cryopreserved semen by SARS-CoV-2 could turn such samples into hazardous viral reservoirs.
The study aims to investigate the presence of the virus in semen, identify cells expressing viral receptors ACE2 and TMPRSS2, and evaluate the virus's direct and indirect effects on male reproductive capacity. Objectives include determining if SARS-CoV-2 survives cryopreservation procedures and identifying optimal methods to ensure virus-free cryopreserved semen while separating infected material from male gametes.
The study will recruit 20 men exposed to SARS-CoV-2 and 20 control subjects, all treated at the Humanitas Fertility Center, Department of Gynecology, at the Humanitas Research Hospital. Each participant will provide a semen sample for evaluation. This observational study will not involve clinical interventions or alter regular diagnostic procedures.
Participants undergoing routine tests for medically assisted reproduction and deemed eligible after completing an anamnesis questionnaire will be included. Samples will be processed in the Mucosal Immunology and Microbiota Unit at the Humanitas Clinical Institute.
Using cell biology, molecular biology, and flow cytometry techniques, the study will assess viral contamination, receptor expression in spermatozoa, and inflammatory cytokine levels in seminal fluid after two cryopreservation methods: slow two-step freezing and vitrification. Analyses will cover unprocessed semen and samples exposed in vitro to SARS-CoV-2 under BSL3 conditions.
Additionally, the cellular fraction of semen, including granulocytes, lymphocytes, round cells, and spermatozoa, will undergo phenotype and activation state characterization. The study will evaluate viral contamination in cryopreserved semen and assess the effectiveness of protocols designed to separate infected material from male gametes.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Male subjects, aged 18-50 requiring a semen fluid evaluation. • Positive IgG serological test result | – | – |
| Healthy | – | –Healthy |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- To analyze the effect of the two cryopreservation methods (slow freezing in two stages and vitrification) on semen samples, we propose to include 20 patients who have been exposed to SARS-CoV-2 infection and 20 control subjects.
Key inclusion criteria (10 listed)
- • Male subjects, aged 18-50 requiring a semen fluid evaluation.
- Male subjects, aged 18-50 requiring a semen fluid evaluation.
- Negative IgG serological test result performed within the last month
- Signed informed consent
- Anamnestic test compilation
Key exclusion criteria (11 listed)
- Patient population exclusion criteria:
- Severe male Factor (azoospermia and <200,00 sperm per ejaculate)
- Fever (>38.5 C) in the 60 days before enrolment
- Known history of SARS-CoV-2 infection
- Treated with antibiotic at the time of enrolment or two months before enrolment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
nvestigation of ACE2 and TMPRSS2 mRNA Expression on Spermatozoa in SARS-CoV-2 Infected Semen Samples
Time frame: through study completion, an average of 1 year
investigate the presence of the mRNA encoding ACE2 and TMPRSS2 on spermatozoa of SARS-CoV-2 semen samples
3 secondary outcomes
Impact of Cryopreservation Methods on the Presence of Viral RNA in SARS-CoV-2 Infected Semen: A Comparison of Two-Step Cryogenic Freezing and Vitrification
Time frame: through study completion, an average of 1 year
valuation of the Presence of the SARS-CoV-2 Viral Genome in Semen Samples"
Time frame: through study completion, an average of 1 year
Immune profiling
Time frame: through study completion, an average of 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID 19, run by Istituto Clinico Humanitas at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
nvestigation of ACE2 and TMPRSS2 mRNA Expression on Spermatozoa in SARS-CoV-2 Infected Semen Samples (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2024.