Analysis of Toxins in Follicle Fluid

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Infertility Treatment Center Dortmund
Sponsor:
Collaborators:
TU Dortmund University
Ferring Pharmaceuticals
Information provided by (Responsible Party):
Infertility Treatment Center Dortmund
ClinicalTrials.gov Identifier:
NCT01385605
First received: June 29, 2011
Last updated: August 28, 2015
Last verified: August 2015
  Purpose

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
Environmental Exposure to Harmful Algae and Toxins
Female Subfertility

Study Type: Observational
Official Title: Analysis of Toxins in Follicle Fluid From Women With Unfulfilled Pregnancy

Resource links provided by NLM:


Further study details as provided by Infertility Treatment Center Dortmund:

Primary Outcome Measures:
  • Pregnancy [ Time Frame: 14 days after ICSI treatment ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

follicular fluid


Estimated Enrollment: 250
Study Start Date: August 2015
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
female patients
ICSI treatment because of male 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.

  Eligibility

Ages Eligible for Study:   18 Years to 39 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

female patients seeking ICSI treatment because of male subfertiliy

Criteria

Inclusion Criteria:

  • healthy females without sterility factors

Exclusion Criteria:

  • job-related exposition to pollutants
  • low responder
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01385605

Contacts
Contact: Stefan Dieterle 00492315575450 dieterle@ivf-dortmund.de

Locations
Germany
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
Investigators
Principal Investigator: Stefan Dieterle Infertility Treatment Center Dortmund
  More Information

No publications provided

Responsible Party: Infertility Treatment Center Dortmund
ClinicalTrials.gov Identifier: NCT01385605     History of Changes
Other Study ID Numbers: Toxins FF 2015
Study First Received: June 29, 2011
Last Updated: August 28, 2015
Health Authority: Germany: Ethics Commission

ClinicalTrials.gov processed this record on August 31, 2015