Analysis of Toxins in Follicle Fluid

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01385605
Recruitment Status : Recruiting
First Posted : June 30, 2011
Last Update Posted : March 20, 2018
TU Dortmund University
Ferring Pharmaceuticals
Information provided by (Responsible Party):
Infertility Treatment Center Dortmund

Brief 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. 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.

Condition or disease
Environmental Exposure to Harmful Algae and Toxins Female Subfertility

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 Type : Observational
Estimated Enrollment : 250 participants
Observational Model: Other
Time Perspective: Other
Official Title: Analysis of Toxins in Follicle Fluid From Women With Unfulfilled Pregnancy
Study Start Date : August 2015
Actual Primary Completion Date : February 28, 2018
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Infertility

female patients
ICSI treatment because of male subfertility

Primary Outcome Measures :
  1. Pregnancy [ Time Frame: 14 days after ICSI treatment ]

Biospecimen Retention:   Samples Without DNA
follicular fluid

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 39 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
female patients seeking ICSI treatment because of male subfertiliy

Inclusion Criteria:

  • healthy females without sterility factors

Exclusion Criteria:

  • job-related exposition to pollutants
  • low responder

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01385605

Contact: Stefan Dieterle 00492315575450

Infertility treatment center Dortmund Recruiting
Dortmund, NRW, Germany, 44135
Contact: Stefan Dieterle    00492315575450      
Principal Investigator: Stefan Dieterle         
Sponsors and Collaborators
Infertility Treatment Center Dortmund
TU Dortmund University
Ferring Pharmaceuticals
Principal Investigator: Stefan Dieterle Infertility Treatment Center Dortmund

Responsible Party: Infertility Treatment Center Dortmund Identifier: NCT01385605     History of Changes
Other Study ID Numbers: Toxins FF 2015
First Posted: June 30, 2011    Key Record Dates
Last Update Posted: March 20, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Infertility, Female
Genital Diseases, Male
Genital Diseases, Female