Male InfertilityNCT06210568
Oxidative Stress and Male Infertility.
An observational study of Male Infertility, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
Study Aims: To evaluate the impact of oxidative and nitrosative stress, as well as DNA methylation, on male reproductive health. This is achieved by analyzing urinary biomarkers: 8-oxoGua, 8-oxoGuo, 8-oxodGuo, 3-nitrotyrosine (3-NO2Tyr), 5-methylcytidine (5-MeCyt), and cotinine in infertile and fertile males. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men only
- Conditions the study is for
- Male Infertility
- How many people
- 800 participants
- Where
- 1 siteItaly
- Study dates
- 27 Jun 2023to 30 Jun 2025
- 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
- Adult
Study population: The study includes 800 males in two groups. Group 1: 400 males from the Center for Reproductive Sciences, aged 18-50, diagnosed with infertility after over 12 months of unsuccessful conception (ART criteria, law 40/2004). Exclusions: clear infertility diagnoses (endocrinological disorders, testicular trauma, vasectomy, epididymitis, orchitis, cryptorchidism, varicocele, azoospermia), past genital radiological treatments, abnormal WHO creatinuria (0.3-3 grams). Group 2: 400 healthy males from Obstetrics and Gynecology, aged 18-50, who fathered a child naturally within 12 months. Exclusions: ART conception, over 12 months for conception, abnormal WHO creatinuria levels. This diverse population enables analyzing oxidative stress's role in male infertility, comparing infertile and fertile males' biological markers and health profiles.
Who may be able to join
- Infertile Male Patients: a diagnosis of couple infertility due to no conception for over 12 months (as per the access criteria for Assisted Reproductive Technology defined by law 40/2004), aged between 18 and 50 years, and having signed informed consent.
- Fertile Males:Inclusion criteria are having fathered at least one child, aged between 18 and 50 years, and having signed informed consent.
Who cannot join
- Infertile Male Patients: Exclusion criteria include a clear diagnosis of infertility due to established clinical evidence (evident endocrinological disorders, previous testicular trauma, vasectomy, epididymitis, orchitis, cryptorchidism, varicocele), inability to produce a useful semen sample for analysis (azoospermia), past diseases that involved radiological therapies in the genital area, and creatinuria levels outside the WHO normal range (0.3-3 grams).
- Fertile Males:conception using assisted reproductive techniques and a waiting time of more than 12 months for conception, as well as creatinuria levels outside the WHO normal range (0.3-3 grams).
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
IRCCS San Raffaele
Milan, MI, 20132
Luca Pagliardini, +39 02 2643 4834, pagliardini.luca@hsr.it
About this study
Official title: Role of Oxidative Stress in Male Infertility: an Observational Case-control Study
Study Aims:
To evaluate the impact of oxidative and nitrosative stress, as well as DNA methylation, on male reproductive health. This is achieved by analyzing urinary biomarkers: 8-oxoGua, 8-oxoGuo, 8-oxodGuo, 3-nitrotyrosine (3-NO2Tyr), 5-methylcytidine (5-MeCyt), and cotinine in infertile and fertile males.
Study Design:
A prospective observational case-control study comparing infertile male patients (cases) from a reproductive sciences center with fertile male volunteers (controls) from a gynecology and obstetrics department. The study focuses on understanding the role of oxidative stress in male infertility and its implications for assisted reproductive techniques.
Read the detailed description
Infertility affects approximately 15% of couples in their reproductive age. Male factors contribute to 45-50% of infertility cases, with 7% of the global male population diagnosed as infertile. Oxidative stress, defined as an imbalance between reactive oxygen species (ROS) and antioxidants, plays a significant role in semen quality degradation. High levels of ROS, unbalanced by antioxidant mechanisms, damage spermatozoa, affecting motility and morphology, and compromising their fertilizing ability. Excessive ROS production, antioxidant depletion, and inactivation or reduced production of antioxidant enzymes contribute to this imbalance. Oxidative stress not only induces lipid peroxidation in sperm membranes but also impacts DNA integrity and increases apoptosis rates. It is estimated to be a significant factor in 30-80% of male infertility cases. Oxidative and nitrosative stress are interrelated; increased ROS levels can interact with nitrogen species, causing further reproductive function damage. Urinary oxidized nucleic acid bases, particularly 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), serve as biomarkers of oxidative stress. Additionally, DNA methylation plays a crucial role in biological processes, with 5-methylcytidine (5-MeCyt) acting as an epigenetic biomarker.
Objectives:
The primary objective is to assess the role of oxidative, nitrosative stress, and DNA methylation on male reproductive health by evaluating urinary biomarkers: 8-oxoGua, 8-oxoGuo, 8-oxodGuo, 3-nitrotyrosine (3-NO2Tyr), 5-MeCyt, and cotinine. The secondary objectives include evaluating semen quality parameters impacted by oxidative stress and identifying potential environmental and lifestyle exposure sources contributing to oxidative stress.
Study Design:
This monocentric, prospective observational study will involve two patient groups: infertile male patients ("cases") attending the Center for Reproductive Sciences and fertile male volunteers ("controls") from the Department of Gynecology and Obstetrics. Procedures for patients and volunteers are additional to the study protocol and not experimental in nature. The study aims to provide a comprehensive understanding of oxidative stress in male infertility and its potential impact on assisted reproductive techniques.
- Conditions
- Male Infertility
- Being tested
- no intervention
- Medical subject headings
- Infertility, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
no interventionOther
no intervention
| Study group | Role | What they receive |
|---|---|---|
| Infertile Male Patients | Not described Receives: Other: no intervention | |
| Fertile males | Not described Receives: Other: no intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the impact of oxidative and nitrosative stress, as well as DNA methylation, on male reproductive health.
Analyze urinary biomarkers: 8-oxoGua, 8-oxoGuo, 8-oxodGuo, 3-nitrotyrosine (3-NO2Tyr), 5-methylcytidine (5-MeCyt), and cotinine in infertile and fertile males.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2024
- Study start27 Jun 2023
- Primary completion30 Jun 2024 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Male InfertilityStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe 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
- 800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Enrico Papaleo, IRCCS San Raffaele
- Investigators
- Enrico Papaleo, Study director, IRCCS San RaffaeleLuca Pagliardini, Principal investigator, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06210568
- Sponsor's protocol ID
- INAIL OSES2022
- Status last verified
- Jan 2024
- First submitted
- 8 Jan 2024
- Last updated
- 18 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Oxidative Stress in Male Infertility: an Observational Case-control Study
- ClinicalTrials.gov ID
- NCT06210568
- Acronym / sponsor ID
- INAIL OSES2022
- Conditions
- Male Infertility
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 27 Jun 2023 (actual)
- Primary completion
- 30 Jun 2024 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 18 Jan 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.
Study Aims:
To evaluate the impact of oxidative and nitrosative stress, as well as DNA methylation, on male reproductive health. This is achieved by analyzing urinary biomarkers: 8-oxoGua, 8-oxoGuo, 8-oxodGuo, 3-nitrotyrosine (3-NO2Tyr), 5-methylcytidine (5-MeCyt), and cotinine in infertile and fertile males.
Study Design:
A prospective observational case-control study comparing infertile male patients (cases) from a reproductive sciences center with fertile male volunteers (controls) from a gynecology and obstetrics department. The study focuses on understanding the role of oxidative stress in male infertility and its implications for assisted reproductive techniques.
Detailed description
Infertility affects approximately 15% of couples in their reproductive age. Male factors contribute to 45-50% of infertility cases, with 7% of the global male population diagnosed as infertile. Oxidative stress, defined as an imbalance between reactive oxygen species (ROS) and antioxidants, plays a significant role in semen quality degradation. High levels of ROS, unbalanced by antioxidant mechanisms, damage spermatozoa, affecting motility and morphology, and compromising their fertilizing ability. Excessive ROS production, antioxidant depletion, and inactivation or reduced production of antioxidant enzymes contribute to this imbalance. Oxidative stress not only induces lipid peroxidation in sperm membranes but also impacts DNA integrity and increases apoptosis rates. It is estimated to be a significant factor in 30-80% of male infertility cases. Oxidative and nitrosative stress are interrelated; increased ROS levels can interact with nitrogen species, causing further reproductive function damage. Urinary oxidized nucleic acid bases, particularly 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), serve as biomarkers of oxidative stress. Additionally, DNA methylation plays a crucial role in biological processes, with 5-methylcytidine (5-MeCyt) acting as an epigenetic biomarker.
Objectives:
The primary objective is to assess the role of oxidative, nitrosative stress, and DNA methylation on male reproductive health by evaluating urinary biomarkers: 8-oxoGua, 8-oxoGuo, 8-oxodGuo, 3-nitrotyrosine (3-NO2Tyr), 5-MeCyt, and cotinine. The secondary objectives include evaluating semen quality parameters impacted by oxidative stress and identifying potential environmental and lifestyle exposure sources contributing to oxidative stress.
Study Design:
This monocentric, prospective observational study will involve two patient groups: infertile male patients ("cases") attending the Center for Reproductive Sciences and fertile male volunteers ("controls") from the Department of Gynecology and Obstetrics. Procedures for patients and volunteers are additional to the study protocol and not experimental in nature. The study aims to provide a comprehensive understanding of oxidative stress in male infertility and its potential impact on assisted reproductive techniques.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Infertile Male Patients | – | Other: no intervention |
| Fertile males | – | Other: no intervention |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Age groups
- Adult
- Study population
- The study includes 800 males in two groups. Group 1: 400 males from the Center for Reproductive Sciences, aged 18-50, diagnosed with infertility after over 12 months of unsuccessful conception (ART criteria, law 40/2004). Exclusions: clear infertility diagnoses (endocrinological disorders, testicular trauma, vasectomy, epididymitis, orchitis, cryptorchidism, varicocele, azoospermia), past genital radiological treatments, abnormal WHO creatinuria (0.3-3 grams). Group 2: 400 healthy males from Obstetrics and Gynecology, aged 18-50, who fathered a child naturally within 12 months. Exclusions: ART conception, over 12 months for conception, abnormal WHO creatinuria levels. This diverse population enables analyzing oxidative stress's role in male infertility, comparing infertile and fertile males' biological markers and health profiles.
Key inclusion criteria (2 listed)
- Infertile Male Patients: a diagnosis of couple infertility due to no conception for over 12 months (as per the access criteria for Assisted Reproductive Technology defined by law 40/2004), aged between 18 and 50 years, and having signed informed consent.
- Fertile Males:Inclusion criteria are having fathered at least one child, aged between 18 and 50 years, and having signed informed consent.
Key exclusion criteria (2 listed)
- Infertile Male Patients: Exclusion criteria include a clear diagnosis of infertility due to established clinical evidence (evident endocrinological disorders, previous testicular trauma, vasectomy, epididymitis, orchitis, cryptorchidism, varicocele), inability to produce a useful semen sample for analysis (azoospermia), past diseases that involved radiological therapies in the genital area, and creatinuria levels outside the WHO normal range (0.3-3 grams).
- Fertile Males:conception using assisted reproductive techniques and a waiting time of more than 12 months for conception, as well as creatinuria levels outside the WHO normal range (0.3-3 grams).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| no interventionno intervention | Other | Fertile males, Infertile Male Patients |
Primary outcome
To evaluate the impact of oxidative and nitrosative stress, as well as DNA methylation, on male reproductive health.
Time frame: 2 years
Analyze urinary biomarkers: 8-oxoGua, 8-oxoGuo, 8-oxodGuo, 3-nitrotyrosine (3-NO2Tyr), 5-methylcytidine (5-MeCyt), and cotinine in infertile and fertile males.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2024.
- Individual participant dataSharing planned: No
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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.
Enrico Papaleo study director
IRCCS San Raffaele
Luca Pagliardini principal investigator
IRCCS San Raffaele
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 Male Infertility, run by IRCCS San Raffaele 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 2 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 18 Jan 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Luca Pagliardini (+39 02 2643 4834, pagliardini.luca@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the impact of oxidative and nitrosative stress, as well as DNA methylation, on male reproductive health. (time frame: 2 years). 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 18 Jan 2024; AzTrials last refreshed its copy on 6 Nov 2026.