Environmental Exposure to Harmful Algae and ToxinsNCT01385605
Analysis of Toxins in Follicle Fluid
An observational study of Environmental Exposure to Harmful Algae and Toxins and Female Subfertility, run by Infertility Treatment Center Dortmund at 1 site in Germany.
Trial summary
Environmental pollutants might be jointly responsible for increase of infertility among women. Especially endocrin active substances seem to be of particular importance. These substances are chemicals which interfere with the physiological system of humans and animals. Read more about this study
- Who is it for?
- Ages 18 to 39 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Environmental Exposure to Harmful Algae and Toxins, Female Subfertility
- How many people
- 210 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2015to 23 Feb 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 39 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: female patients seeking ICSI treatment because of male subfertiliy
Who may be able to join
- healthy females without sterility factors
Who cannot join
- job-related exposition to pollutants
- low responder
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: Analysis of Toxins in Follicle Fluid From Women With Unfulfilled Pregnancy
Environmental pollutants might be jointly responsible for increase of infertility among women. Especially endocrin active substances seem to be of particular importance. These substances are chemicals which interfere with the physiological system of humans and animals. They have a negative impact on the endocrine system and disturb the functions of organs whose hormones regulate the male and female reproductive system.
It is known that exposition to these chemicals lead to subfertility, infertility, raised abortions, birth defects and ovarian malfunction.
Read more
Additionally it was shown that human embryos have a decreased cleavage rate after IVF when developing from oocytes with elevated concentrations of environmental pollutants.
In this study the main focus concentrates on Nonylphenols (NP). Follicular fluids of women with subfertility will be analyzed by a newly developed principle including HPLC and NMR-Spectroscopy. This enables quantitative and qualitative analysis of enantiomers of NP.
The results will allow risk estimations for several endocrine active substances, especially NP.
Additionally conclusions concerning the correlation between thes substances and subfertility can be drawn.
Read the detailed description
Exposure to environmental toxins may be responsible for female infertility. In particular substances known as endocrine disrupting chemicals (EDCs) may play a crucial role. These environmental toxins are either synthetic chemicals used in industry, agriculture or pharmacy, or natural chemicals found in food. Thus, exposure to EDCs can occur at different ways, e.g. drinking of contaminated water, breathing of contaminated air, or simple food intake. Despite most EDCs exhibit a long half-life, continuous accumulation of endocrine active substances will occur globally. In addition, low water-solubility and extremely high lipid-solubility promoted the accumulation within the human organism.
Consequently, EDCs may harm human health. It is known that EDCs lead to the disruption of the physiological system and that endocrine active substances interfere with the endocrine homeostasis. Moreover, EDCs alter organs that regulate male and female hormonal regulation crucial for reproduction fitness. Sterility and infertility, dysfunctional ovaries and an increased risk of abortions are discussed as critical consequences of EDC exposure.
It was shown that some endocrine active substances are present in the follicle fluid of women with unfilled pregnancy. Oocytes from follicles with an increased concentration of environmental toxins exhibit a reduced developmental potential. Additionally, women with an increased level of the EDC Bisphenol A tend to exhibit an increased risk of aborts.
Nonylphenol (NP) belongs to the class of endocrine active substances and are of special importance due to their high longevity and toxic characteristics. Nonylphenol is a multi-compound mixture that becomes generated as a by-product after degeneration of nonylphenol-ethoxylates (NPE) due to biological wastewater treatment. NPE are components of several cleaning agents, emulsifiers, dispersing agents and pesticides. NP is a mixture that consists mainly of para-substituted mono-alkylphenols with different isomeric nonyl-groups. Despite their high persistence and toxicity, exposure to NP induces alterations of the endocrine homeostasis in water organism, bird and mammals. NP can potentially bind to different hormone receptors (e.g. estrogen receptors, progesteron receptors and androgen receptors) and induce or modulate hormone-dependent downstream pathways. The influence regarding the reproductive fitness is much higher in females compared to males.
In the planned study, the follicle fluid will be analyzed in particular for the appearance of NP. Analysis will be done at the Institute of environmental research (Dortmund) in the group of Prof. Spiteller. Basis of this analysis is a chiral gas chromatography - mass spectroscopy that is optimized for the qualitative and quantitative assessment of NP isomers. For further details, see trial design and research setting.
Until now, two preliminary test series were done with at all 34 test persons. Within the first series of measurement, four patients exhibited an increased NP concentration in the follicle fluid (13.7 to 20.9 ng/g compared to 2.1 to 9 ng/g). In the second test series, the NP concentration was less prominent in all analyzed patients (average about 1 ng/ml), but detection of NP was still possible. Thus, NP was detected in all of the analyzed follicle fluid samples. However, the different NP concentration among all tested patients claims certainly the question, whether and how different concentration induce biological effects. The analysis of a large proband cohort regarding the appearance of NP within the follicle fluid facilitates the possibility to estimate a risk appraisal in patients with an unfilled pregnancy. Several parameters will be included for the evaluation: number of MII oocytes, fertilization rate, embryo quality, pregnancy rate, implantation rate and rate of abortions. Despite the duration of infertility and the number of previous IVF cycles will be considered, it is feasible to determine a correlation between the appearance of NP within the follicle fluid and the unfilled desire to have children.
- 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 |
|---|---|---|
| female patients | ICSI treatment because of male subfertility |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pregnancy
Measured: 14 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 Jun 2011 (estimated)
- Study startAug 2015
- Primary completion30 Jun 2020
- Study completion23 Feb 2021
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 Environmental Exposure to Harmful Algae and ToxinsStudies 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
- 210 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, Principal investigator, Infertility Treatment Center Dortmund
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01385605
- Sponsor's protocol ID
- Toxins FF 2015
- Status last verified
- Mar 2021
- First submitted
- 29 Jun 2011
- Last updated
- 8 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Bullach A, Trapphoff T, Zuhlke S, Spiteller M, Dieterle S. Impact of Nonylphenols and Polyhalogenated Compounds in Follicular Fluid on the Outcome of Intracytoplasmic Sperm Injection. Reprod Sci. 2021 Aug;28(8):2118-2128. doi: 10.1007/s43032-021-00472-y. Epub 2021 Feb 23.
PubMed 33620705
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of Toxins in Follicle Fluid From Women With Unfulfilled Pregnancy
- ClinicalTrials.gov ID
- NCT01385605
- Acronym / sponsor ID
- Toxins FF 2015
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 210 participants (actual)
- Lead sponsor
- Infertility Treatment Center DortmundUniversity, hospital or other
- Collaborators
- TU Dortmund University, Ferring Pharmaceuticals
- Study start
- Aug 2015
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 23 Feb 2021 (actual)
- First posted
- 30 Jun 2011 (estimated)
- 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.
Environmental pollutants might be jointly responsible for increase of infertility among women. Especially endocrin active substances seem to be of particular importance. These substances are chemicals which interfere with the physiological system of humans and animals. They have a negative impact on the endocrine system and disturb the functions of organs whose hormones regulate the male and female reproductive system.
It is known that exposition to these chemicals lead to subfertility, infertility, raised abortions, birth defects and ovarian malfunction.
Additionally it was shown that human embryos have a decreased cleavage rate after IVF when developing from oocytes with elevated concentrations of environmental pollutants.
In this study the main focus concentrates on Nonylphenols (NP). Follicular fluids of women with subfertility will be analyzed by a newly developed principle including HPLC and NMR-Spectroscopy. This enables quantitative and qualitative analysis of enantiomers of NP.
The results will allow risk estimations for several endocrine active substances, especially NP.
Additionally conclusions concerning the correlation between thes substances and subfertility can be drawn.
Detailed description
Exposure to environmental toxins may be responsible for female infertility. In particular substances known as endocrine disrupting chemicals (EDCs) may play a crucial role. These environmental toxins are either synthetic chemicals used in industry, agriculture or pharmacy, or natural chemicals found in food. Thus, exposure to EDCs can occur at different ways, e.g. drinking of contaminated water, breathing of contaminated air, or simple food intake. Despite most EDCs exhibit a long half-life, continuous accumulation of endocrine active substances will occur globally. In addition, low water-solubility and extremely high lipid-solubility promoted the accumulation within the human organism.
Consequently, EDCs may harm human health. It is known that EDCs lead to the disruption of the physiological system and that endocrine active substances interfere with the endocrine homeostasis. Moreover, EDCs alter organs that regulate male and female hormonal regulation crucial for reproduction fitness. Sterility and infertility, dysfunctional ovaries and an increased risk of abortions are discussed as critical consequences of EDC exposure.
It was shown that some endocrine active substances are present in the follicle fluid of women with unfilled pregnancy. Oocytes from follicles with an increased concentration of environmental toxins exhibit a reduced developmental potential. Additionally, women with an increased level of the EDC Bisphenol A tend to exhibit an increased risk of aborts.
Nonylphenol (NP) belongs to the class of endocrine active substances and are of special importance due to their high longevity and toxic characteristics. Nonylphenol is a multi-compound mixture that becomes generated as a by-product after degeneration of nonylphenol-ethoxylates (NPE) due to biological wastewater treatment. NPE are components of several cleaning agents, emulsifiers, dispersing agents and pesticides. NP is a mixture that consists mainly of para-substituted mono-alkylphenols with different isomeric nonyl-groups. Despite their high persistence and toxicity, exposure to NP induces alterations of the endocrine homeostasis in water organism, bird and mammals. NP can potentially bind to different hormone receptors (e.g. estrogen receptors, progesteron receptors and androgen receptors) and induce or modulate hormone-dependent downstream pathways. The influence regarding the reproductive fitness is much higher in females compared to males.
In the planned study, the follicle fluid will be analyzed in particular for the appearance of NP. Analysis will be done at the Institute of environmental research (Dortmund) in the group of Prof. Spiteller. Basis of this analysis is a chiral gas chromatography - mass spectroscopy that is optimized for the qualitative and quantitative assessment of NP isomers. For further details, see trial design and research setting.
Until now, two preliminary test series were done with at all 34 test persons. Within the first series of measurement, four patients exhibited an increased NP concentration in the follicle fluid (13.7 to 20.9 ng/g compared to 2.1 to 9 ng/g). In the second test series, the NP concentration was less prominent in all analyzed patients (average about 1 ng/ml), but detection of NP was still possible. Thus, NP was detected in all of the analyzed follicle fluid samples. However, the different NP concentration among all tested patients claims certainly the question, whether and how different concentration induce biological effects. The analysis of a large proband cohort regarding the appearance of NP within the follicle fluid facilitates the possibility to estimate a risk appraisal in patients with an unfilled pregnancy. Several parameters will be included for the evaluation: number of MII oocytes, fertilization rate, embryo quality, pregnancy rate, implantation rate and rate of abortions. Despite the duration of infertility and the number of previous IVF cycles will be considered, it is feasible to determine a correlation between the appearance of NP within the follicle fluid and the unfilled desire to have children.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| female patients | – | –ICSI treatment because of male subfertility |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- female patients seeking ICSI treatment because of male subfertiliy
Key inclusion criteria (1 listed)
- healthy females without sterility factors
Key exclusion criteria (2 listed)
- job-related exposition to pollutants
- low responder
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
Pregnancy
Time frame: 14 days after ICSI treatment
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 8 Mar 2021.
- Derived from this study: PubMed 33620705Bullach A, Trapphoff T, Zuhlke S, Spiteller M, Dieterle S. Impact of Nonylphenols and Polyhalogenated Compounds in Follicular Fluid on the Outcome of Intracytoplasmic Sperm Injection. Reprod Sci. 2021 Aug;28(8):2118-2128. doi: 10.1007/s43032-021-00472-y. Epub 2021 Feb 23.
- 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 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 Environmental Exposure to Harmful Algae and Toxins and Female Subfertility, 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 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: finished, as of the sponsor's last update on 8 Mar 2021. 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?
Pregnancy (time frame: 14 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 NCT01385605, 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 8 Mar 2021.