Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03414567 |
| Other study ID # |
Nicotine Folicular Fluid 2018 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2018 |
| Est. completion date |
May 28, 2024 |
Study information
| Verified date |
May 2024 |
| Source |
Infertility Treatment Center Dortmund |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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.
