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Presence of Toxins From Smoking in the Follicular Fluid of Women Undergoing Intracytoplasmic Sperm Injection Treatment

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ClinicalTrials.gov Identifier: NCT03414567
Recruitment Status : Recruiting
First Posted : January 30, 2018
Last Update Posted : March 14, 2018
Sponsor:
Collaborators:
TU Dortmund University
Ferring Pharmaceuticals
Information provided by (Responsible Party):
Infertility Treatment Center Dortmund

Brief Summary:

Smoking is associated with many adverse health effects like circulatory disorders, pulmonary diseases or heart diseases. It was also shown that smoking correlates with a significantly higher risk for miscarriage, preterm birth or a significantly decreased implantation rate or life birth rate, thus affects the chance to have children.

Combustion of tobacco products results in more than 4.000 toxic and/or carcinogenic substances. Examples of such substances are the carcinogenic substance Benzo(a)pyrene or nicotine and its main degradation product cotinine. Although the adverse effects of these substances were analyzed in many biological systems (e.g. cell culture, mouse model systems), less is known about the bio-accumulation in human tissue, especially in ovarian tissue or the follicular fluid (FF).

The aim of this study is therefore to analyze the bio-accumulation of nicotine, cotinine and Benzo(a)pyrene in the follicular fluid of women with the unfulfilled desire to have children undergoing an intracytoplasmic sperm injection (ICSI) treatment. The analysis will be performed using a sensitive gas chromatography-mass spectroscopy (GC) in a control group (non-smoker) and a study group (smoker). For each group, a correlation analysis between the amount of toxic and/or carcinogenic substances and the clinical outcome (e.g. clinical pregnancy rate, fertilization rate) will be performed. In combination with a patient questionnaire, it will be possible to analyze the risk of smoking, the bio-accumulation of toxic substances in the follicular fluid, and the chance to have children.


Condition or disease
Exposure to Toxins From Smoking Female Infertility

Detailed Description:

The desire to have children can be influenced by a number of factors. Besides hormonal factors, age and body weight, or genetic disorders, smoking may play an important role. It was shown that cigarette smoking correlates with a significantly decreased implantation and life birth rate, and a significantly higher risk for miscarriage or preterm birth. Moreover, limitations of the oocyte quality, a decreased thickness of the Zona Pellucida, or spindle disorders were reported. Overall, smokers are much less likely to succeed in pregnancy as published by the American Society for Reproductive Medicine (ASRM) in 2012. Although general tobacco consumption in Germany is declining, about 30% of women of childbearing age (between 18 and 45 years) smoke (German Federal Office of Statistics, 2013).

Combustion of tobacco products (and additives like glycerin, menthol or sorbic acid) results in the formation of more than 4.000 toxic and/or carcinogenic substances. Two of these substances are nicotine and its main degradation product cotinine, another example is the carcinogenic substance Benzo(a)pyrene. The nicotine clearance in the human body is relatively fast - the half-life of nicotine is less than 2 hours in the human body. However, cotinine with a half-life of more than 16 hours is an appropriate biomarker to study the bio-accumulation of nicotine/cotinine. The effect of nicotine, cotinine or Benzo(a)pyrene on the reproductive system has already been investigated in various animal model systems and some clinical trials. For example, nicotine limits progesterone and estrogen biosynthesis, reduces peripheral blood flow, and reduces contractility of the fallopian tubes and uterus. Benzo(a)pyrene impairs cell proliferation as well as estrogen biosynthesis. It has also been implicated in DNA damaging mechanisms.

Nevertheless, little is known about the bio-accumulation of these toxic substances in human tissue, especially in the reproductive system (e.g. ovarian tissue or the follicular fluid). Some published studies were additionally limited because of their limited sample size (n<50) or non-sensitive analyzing tools (e.g. enzyme-linked immunosorbent assay (ELISA) analysis). The aim of this study is therefore to analyze the bio-accumulation of nicotine, cotinine and Benzo(a)pyrene in the follicular fluid of women with the unfulfilled desire to have children undergoing an intracytoplasmic sperm injection treatment using an ultra-sensitive gas chromatography-mass spectroscopy in a control group (non-smoker) and a study group (smoker). For each group, a sample size of n=150 will be included. This makes it possible to perform a statistical analysis regarding the presence of smoking pollutants in the follicular fluid and the associated clinical parameters (e.g. clinical pregnancy outcome, oocyte count, fertilization rate) between the study and control group. In combination with a patient questionnaire, it will be possible to identify the risk of smoking, the bio-accumulation of toxic substances in the follicular fluid and the desire to have children.


Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Other
Time Perspective: Other
Official Title: Presence of Toxins From Smoking in the Follicular Fluid of Women With the Desire to Have Children Undergoing Intracytoplasmic Sperm Injection Treatment
Actual Study Start Date : March 1, 2018
Estimated Primary Completion Date : August 30, 2019
Estimated Study Completion Date : December 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Infertility Smoking

Group/Cohort
Control Group
Non-smoker
Study Group
Smoker



Primary Outcome Measures :
  1. Clinical pregnancy rate [ Time Frame: 28 days after ICSI treatment ]
    Presence of amniotic cavity and heartbeat after embryo transfer


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 40 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 subfertility
Criteria

Inclusion Criteria:

- healthy females without sterility factors

Exclusion Criteria:

  • Endometriosis
  • Polycystic ovary syndrome (PCO)
  • Neoplasia (ovary, Uterus, breast)
  • Anti-Müllerian hormone (AMH) <1 ng/ml

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 ClinicalTrials.gov identifier (NCT number): NCT03414567


Contacts
Contact: Stefan Dieterle, MD 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, MD Infertility Treatment Center Dortmund

Responsible Party: Infertility Treatment Center Dortmund
ClinicalTrials.gov Identifier: NCT03414567     History of Changes
Other Study ID Numbers: Nicotine Folicular Fluid 2018
First Posted: January 30, 2018    Key Record Dates
Last Update Posted: March 14, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Infertility Treatment Center Dortmund:
Follicular fluid
nicotine
cotinine
Benzo(a)pyrene

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