Exposure to Toxins from SmokingNCT03414567
Presence of Toxins from Smoking in the Follicular Fluid of Women Undergoing Intracytoplasmic Sperm Injection Treatment
An observational study of Exposure to Toxins from Smoking and Female Infertility, run by Infertility Treatment Center Dortmund at 1 site in Germany.
Trial summary
Smoking is associated with many adverse health effects like circulatory disorders, pulmonary diseases or heart diseases. It was also shown that smoking correlates with a significantly higher risk for miscarriage, preterm birth or a significantly decreased implantation rate or life birth rate, thus affects the chance… Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Exposure to Toxins from Smoking, Female Infertility
- How many people
- 320 participants
- Where
- 1 siteGermany
- Study dates
- 1 Mar 2018to 28 May 2024
- 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 40 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: female patients seeking ICSI treatment because of male subfertility
Who may be able to join
- healthy females without sterility factors
Who cannot join
- Endometriosis
- Polycystic ovary syndrome (PCO)
- Neoplasia (ovary, Uterus, breast)
- Anti-Müllerian hormone (AMH) <1 ng/ml
Trial locations and contacts
1 site in 1 country.
Germany1 site
Infertility treatment center Dortmund
Dortmund, North Rhine-Westphalia, 44135
About this study
Official title: Presence of Toxins from Smoking in the Follicular Fluid of Women with the Desire to Have Children Undergoing Intracytoplasmic Sperm Injection Treatment
Smoking is associated with many adverse health effects like circulatory disorders, pulmonary diseases or heart diseases. It was also shown that smoking correlates with a significantly higher risk for miscarriage, preterm birth or a significantly decreased implantation rate or life birth rate, thus affects the chance to have children.
Combustion of tobacco products results in more than 4.000 toxic and/or carcinogenic substances. Examples of such substances are the carcinogenic substance Benzo(a)pyrene or nicotine and its main degradation product cotinine. Although the adverse effects of these substances were analyzed in many biological systems (e.g. cell culture, mouse model systems), less is known about the bio-accumulation in human tissue, especially in ovarian tissue or the follicular fluid (FF).
The aim of this study is therefore to analyze the bio-accumulation of nicotine, cotinine and Benzo(a)pyrene in the follicular fluid of women with the unfulfilled desire to have children undergoing an intracytoplasmic sperm injection (ICSI) treatment. The analysis will be performed using a sensitive gas chromatography-mass spectroscopy (GC) in a control group (non-smoker) and a study group (smoker). For each group, a correlation analysis between the amount of toxic and/or carcinogenic substances and the clinical outcome (e.g. clinical pregnancy rate, fertilization rate) will be performed. In combination with a patient questionnaire, it will be possible to analyze the risk of smoking, the bio-accumulation of toxic substances in the follicular fluid, and the chance to have children.
Read the detailed description
The desire to have children can be influenced by a number of factors. Besides hormonal factors, age and body weight, or genetic disorders, smoking may play an important role. It was shown that cigarette smoking correlates with a significantly decreased implantation and life birth rate, and a significantly higher risk for miscarriage or preterm birth. Moreover, limitations of the oocyte quality, a decreased thickness of the Zona Pellucida, or spindle disorders were reported. Overall, smokers are much less likely to succeed in pregnancy as published by the American Society for Reproductive Medicine (ASRM) in 2012. Although general tobacco consumption in Germany is declining, about 30% of women of childbearing age (between 18 and 45 years) smoke (German Federal Office of Statistics, 2013).
Combustion of tobacco products (and additives like glycerin, menthol or sorbic acid) results in the formation of more than 4.000 toxic and/or carcinogenic substances. Two of these substances are nicotine and its main degradation product cotinine, another example is the carcinogenic substance Benzo(a)pyrene. The nicotine clearance in the human body is relatively fast - the half-life of nicotine is less than 2 hours in the human body. However, cotinine with a half-life of more than 16 hours is an appropriate biomarker to study the bio-accumulation of nicotine/cotinine. The effect of nicotine, cotinine or Benzo(a)pyrene on the reproductive system has already been investigated in various animal model systems and some clinical trials. For example, nicotine limits progesterone and estrogen biosynthesis, reduces peripheral blood flow, and reduces contractility of the fallopian tubes and uterus. Benzo(a)pyrene impairs cell proliferation as well as estrogen biosynthesis. It has also been implicated in DNA damaging mechanisms.
Nevertheless, little is known about the bio-accumulation of these toxic substances in human tissue, especially in the reproductive system (e.g. ovarian tissue or the follicular fluid). Some published studies were additionally limited because of their limited sample size (n<50) or non-sensitive analyzing tools (e.g. enzyme-linked immunosorbent assay (ELISA) analysis). The aim of this study is therefore to analyze the bio-accumulation of nicotine, cotinine and Benzo(a)pyrene in the follicular fluid of women with the unfulfilled desire to have children undergoing an intracytoplasmic sperm injection treatment using an ultra-sensitive gas chromatography-mass spectroscopy in a control group (non-smoker) and a study group (smoker). For each group, a sample size of n=150 will be included. This makes it possible to perform a statistical analysis regarding the presence of smoking pollutants in the follicular fluid and the associated clinical parameters (e.g. clinical pregnancy outcome, oocyte count, fertilization rate) between the study and control group. In combination with a patient questionnaire, it will be possible to identify the risk of smoking, the bio-accumulation of toxic substances in the follicular fluid and the desire to have children.
- Keywords
- Follicular fluid, nicotine, cotinine, Benzo(a)pyrene
- Medical subject headings
- Infertility, Female
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 |
|---|---|---|
| Control Group | Non-smoker | |
| Study Group | Smoker |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical pregnancy rate
Presence of amniotic cavity and heartbeat after embryo transfer
Measured: 28 days after ICSI treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2018
- Study start1 Mar 2018
- Primary completion30 Dec 2023
- Study completion28 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Exposure to Toxins from SmokingStudies of the same condition, open and under way.
- 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
- Other
- Time perspective
- Other
- Enrolment
- 320 participants (actual)
Sponsor and investigators
- Lead sponsor
- Infertility Treatment Center Dortmund
- Sponsor type
- University, hospital or other
- Collaborators
- TU Dortmund University, Ferring Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Stefan Dieterle, MD, Principal investigator, Infertility Treatment Center Dortmund
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03414567
- Sponsor's protocol ID
- Nicotine Folicular Fluid 2018
- Status last verified
- Oct 2024
- First submitted
- 23 Jan 2018
- Last updated
- 4 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Trapphoff T, Ontrup C, Krug S, Dieterle S. Consumption of hookahs, e-cigarettes, and classic cigarettes and the impact on medically assisted reproduction treatment. Sci Rep. 2024 Apr 26;14(1):9597. doi: 10.1038/s41598-024-60251-y.
PubMed 38671174
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Presence of Toxins from Smoking in the Follicular Fluid of Women with the Desire to Have Children Undergoing Intracytoplasmic Sperm Injection Treatment
- ClinicalTrials.gov ID
- NCT03414567
- Acronym / sponsor ID
- Nicotine Folicular Fluid 2018
- Keywords
- Follicular fluid, nicotine, cotinine, Benzo(a)pyrene
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 320 participants (actual)
- Lead sponsor
- Infertility Treatment Center DortmundUniversity, hospital or other
- Collaborators
- TU Dortmund University, Ferring Pharmaceuticals
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 30 Dec 2023 (actual)
- Study completion
- 28 May 2024 (actual)
- First posted
- 30 Jan 2018 (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.
Smoking is associated with many adverse health effects like circulatory disorders, pulmonary diseases or heart diseases. It was also shown that smoking correlates with a significantly higher risk for miscarriage, preterm birth or a significantly decreased implantation rate or life birth rate, thus affects the chance to have children.
Combustion of tobacco products results in more than 4.000 toxic and/or carcinogenic substances. Examples of such substances are the carcinogenic substance Benzo(a)pyrene or nicotine and its main degradation product cotinine. Although the adverse effects of these substances were analyzed in many biological systems (e.g. cell culture, mouse model systems), less is known about the bio-accumulation in human tissue, especially in ovarian tissue or the follicular fluid (FF).
The aim of this study is therefore to analyze the bio-accumulation of nicotine, cotinine and Benzo(a)pyrene in the follicular fluid of women with the unfulfilled desire to have children undergoing an intracytoplasmic sperm injection (ICSI) treatment. The analysis will be performed using a sensitive gas chromatography-mass spectroscopy (GC) in a control group (non-smoker) and a study group (smoker). For each group, a correlation analysis between the amount of toxic and/or carcinogenic substances and the clinical outcome (e.g. clinical pregnancy rate, fertilization rate) will be performed. In combination with a patient questionnaire, it will be possible to analyze the risk of smoking, the bio-accumulation of toxic substances in the follicular fluid, and the chance to have children.
Detailed description
The desire to have children can be influenced by a number of factors. Besides hormonal factors, age and body weight, or genetic disorders, smoking may play an important role. It was shown that cigarette smoking correlates with a significantly decreased implantation and life birth rate, and a significantly higher risk for miscarriage or preterm birth. Moreover, limitations of the oocyte quality, a decreased thickness of the Zona Pellucida, or spindle disorders were reported. Overall, smokers are much less likely to succeed in pregnancy as published by the American Society for Reproductive Medicine (ASRM) in 2012. Although general tobacco consumption in Germany is declining, about 30% of women of childbearing age (between 18 and 45 years) smoke (German Federal Office of Statistics, 2013).
Combustion of tobacco products (and additives like glycerin, menthol or sorbic acid) results in the formation of more than 4.000 toxic and/or carcinogenic substances. Two of these substances are nicotine and its main degradation product cotinine, another example is the carcinogenic substance Benzo(a)pyrene. The nicotine clearance in the human body is relatively fast - the half-life of nicotine is less than 2 hours in the human body. However, cotinine with a half-life of more than 16 hours is an appropriate biomarker to study the bio-accumulation of nicotine/cotinine. The effect of nicotine, cotinine or Benzo(a)pyrene on the reproductive system has already been investigated in various animal model systems and some clinical trials. For example, nicotine limits progesterone and estrogen biosynthesis, reduces peripheral blood flow, and reduces contractility of the fallopian tubes and uterus. Benzo(a)pyrene impairs cell proliferation as well as estrogen biosynthesis. It has also been implicated in DNA damaging mechanisms.
Nevertheless, little is known about the bio-accumulation of these toxic substances in human tissue, especially in the reproductive system (e.g. ovarian tissue or the follicular fluid). Some published studies were additionally limited because of their limited sample size (n<50) or non-sensitive analyzing tools (e.g. enzyme-linked immunosorbent assay (ELISA) analysis). The aim of this study is therefore to analyze the bio-accumulation of nicotine, cotinine and Benzo(a)pyrene in the follicular fluid of women with the unfulfilled desire to have children undergoing an intracytoplasmic sperm injection treatment using an ultra-sensitive gas chromatography-mass spectroscopy in a control group (non-smoker) and a study group (smoker). For each group, a sample size of n=150 will be included. This makes it possible to perform a statistical analysis regarding the presence of smoking pollutants in the follicular fluid and the associated clinical parameters (e.g. clinical pregnancy outcome, oocyte count, fertilization rate) between the study and control group. In combination with a patient questionnaire, it will be possible to identify the risk of smoking, the bio-accumulation of toxic substances in the follicular fluid and the desire to have children.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | – | –Non-smoker |
| Study Group | – | –Smoker |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- female patients seeking ICSI treatment because of male subfertility
Key inclusion criteria (1 listed)
- healthy females without sterility factors
Key exclusion criteria (4 listed)
- Endometriosis
- Polycystic ovary syndrome (PCO)
- Neoplasia (ovary, Uterus, breast)
- Anti-Müllerian hormone (AMH) <1 ng/ml
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
Clinical pregnancy rate
Time frame: 28 days after ICSI treatment
Presence of amniotic cavity and heartbeat after embryo transfer
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 4 Nov 2024.
- Derived from this study: PubMed 38671174Trapphoff T, Ontrup C, Krug S, Dieterle S. Consumption of hookahs, e-cigarettes, and classic cigarettes and the impact on medically assisted reproduction treatment. Sci Rep. 2024 Apr 26;14(1):9597. doi: 10.1038/s41598-024-60251-y.
- Trapphoff et al., 2024 (Consumption of hookahs, e-cigarettes, and classic cigarettes and the impact on medically assisted reproduction treatment)Link provided by the sponsor.
- Individual participant dataSharing planned: No
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.
Stefan Dieterle, MD principal investigator
Infertility Treatment Center Dortmund
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 Exposure to Toxins from Smoking and Female Infertility, run by Infertility Treatment Center Dortmund at 1 site in Germany.
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 1 inclusion and 4 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 4 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 Germany. 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?
Clinical pregnancy rate (time frame: 28 days after ICSI treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03414567, which also lists 1 linked publication.
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 4 Nov 2024.