Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01385605 |
| Other study ID # |
Toxins FF 2015 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 2015 |
| Est. completion date |
February 23, 2021 |
Study information
| Verified date |
March 2021 |
| Source |
Infertility Treatment Center Dortmund |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical 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.
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.
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.
