Analysis of Toxins in Follicle Fluid
Condition: Environmental Exposure to Harmful Algae and Toxins; Female Subfertility
MeSH terms: Infertility; Infertility, Female
Study type: Observational

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.
    

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.
    

Observational model: Other
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        female patients seeking ICSI treatment because of male subfertiliy
      
Biospecimen description: 
      follicular fluid