- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04866329
Female Fertility, Environmental Agents and Stress Oxidant (FERTENOX)
FERTilité féminine, Agents ENvironnementaux et Stress OXydant
Synthetic products used in industrial, pharmaceutical, agro-alimentary or agricultural fields are found in our environment. Thus, humans could be simultaneously exposed to several of these pollutants. Furthermore, these environmental agents exert or could exert adverse actions on fertility, by altering gamete and embryo quality through endocrine disruptor effects or through increase in oxidative stress in gonads (cellular pathway known to be involved in several human reproductive pathologies).
In this context, the objectives of the present project are to obtain descriptive and analytical data on woman and oocyte exposure to several environmental agents (bisphenols, ethynylestradiol and glyphosate). The relation between these pollutant measures in follicular fluid and urine (from women receiving follow-up of in vitro fertilization (IVF) protocol in the University hospital of Tours, France) and the oocyte quality, the IVF and pregnancy successes will be studied. Several oxidative stress biomarkers in blood and follicular fluid will be also measured for these women, who will complete a questionnaire on their lifestyles. Finally, thanks to in vitro approaches, the effects and the mechanisms of action (including oxidative stress) of these pollutants (alone or in cocktails) will be studied on granulosa cells from these patients.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
After being informed about the project Fertenox during a meeting describing about the Fecondation In Vitro protocol, all women patients not opposing to participate in the study and to use individual information will be included in the research during the usual bacteriological exam performed 1-2 months before oocyte pick up in the University hospital. They will receive the questionnaire on their lifestyle during this exam.
On the eve of the oocyte pick up (at the end of ovarian stimulation) during the usual blood collection, three additional tubes of blood will be collected for each patient in the University hospital. Women will also receive the screw-top container for morning-after urine sample and the completion of the lifestyle questionnaire will be checked (some advices will be done if necessary to help patients to fill out the questionnaire). Samples will be treated, aliquoted and stored according to requirements the same day.
The day of the oocyte pick up, the first morning urine will be collected by patients at home (or otherwise in the hospital). The completed questionnaire will be recovered and follicular fluid and granulosa cells will be collected for each woman. Samples will be aliquoted and stored according to requirements the same day. Granulosa cells will be cultured for in vitro approaches in research labs the same day.
Tubes of blood, urine and follicular fluid will be coded and kept at -80°C in the University hospital until their shipment to laboratories, where analyses of pollutants (bisphenols, ethynylestradiol and glyphosate) and analyses of oxidative stress biomarkers (antioxidant vitamins, FRAP), activity of several enzymes (catalase, superoxide dismutase, glutathione peroxidase) and oxidized lipids) will be performed.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Fabrice GUERIF, MD-PhD
- Phone Number: +33 02.47.47.84.76
- Email: fabrice.guerif@univ-tours.fr
Study Contact Backup
- Name: Virginie MAILLARD, PhD
- Phone Number: +33 02.47.42.79.71
- Email: virginie.maillard@inrae.fr
Study Locations
-
-
-
Tours, France, 37044
- Recruiting
- Department of Reproductive Medicine and Biology, Univesity Hospital, Tours
-
Contact:
- Fabrice GUERIF, MD-PhD
-
Contact:
- Claire VIGNAULT, MD
-
Principal Investigator:
- Fabrice GUERIF, MD-PhD
-
Sub-Investigator:
- Claire VIGNAULT, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Woman aged 18 to 43 years old
- First oocyte puncture (IVF rank = 1)
Exclusion Criteria:
- Opposition to data processing
- IVF rank equal or greater than 2
- Egg donation
- Intracytoplasmic Sperm Injection with testicular biopsy
- Intracytoplasmic Sperm Injection with self-preservation straw
- Sperm donation
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
In Vitro Fertilisation protocol
Women followed in the department for an in vitro fertilisation protocol
|
Additional blood sampling at the end of ovarian stimulation monitoring (the eve of the oocyte pick-up)
Collection of the first urine in the morning on the day of the oocyte pick-up
Collection of follicular fluid and granulosa cells during oocyte pick-up.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Presence or absence of ethinylestradiol in follicular fluid
Time Frame: Baseline
|
Assessed by measure of ethinylestradiol in follicular fluid by Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)
|
Baseline
|
Presence or absence of ethinylestradiol in urine
Time Frame: Baseline
|
Assessed by measure of ethinylestradiol in urine by Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)
|
Baseline
|
Presence or absence of bisphenols in follicular fluid
Time Frame: Baseline
|
Assessed by measure of bisphenols in follicular fluid by Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)
|
Baseline
|
Presence or absence of bisphenols in urine
Time Frame: Baseline
|
Assessed by measure of bisphenols in urine by Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)
|
Baseline
|
Presence or absence of glyphosate in follicular fluid
Time Frame: baseline
|
Assessed by measure of glyphosate in follicular fluid by Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)
|
baseline
|
Presence or absence of glyphosate in urine
Time Frame: baseline
|
Assessed by measure of glyphosate in urine by Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)
|
baseline
|
Concentration of ethinylestradiol in follicular fluid
Time Frame: baseline
|
Assessed by concentration of ethinylestradiol in follicular fluid by Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)
|
baseline
|
Concentration of ethinylestradiol in urine
Time Frame: baseline
|
Assessed by concentration of ethinylestradiol in urine by Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)
|
baseline
|
Concentration of bisphenols in follicular fluid
Time Frame: baseline
|
Assessed by concentration of bisphenols in follicular fluid by Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)
|
baseline
|
Concentration of bisphenols in urine
Time Frame: baseline
|
Assessed by concentration of bisphenols in urine by Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)
|
baseline
|
Concentration of glyphosate in follicular fluid
Time Frame: baseline
|
Assessed by concentration of glyphosate in follicular fluid by Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)
|
baseline
|
Concentration of glyphosate in urine
Time Frame: baseline
|
Assessed by concentration of glyphosate in urine by Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)
|
baseline
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Oocyte quality
Time Frame: baseline
|
Assessed by nuclear maturity of each collected punctured oocyte
|
baseline
|
Embryo quality
Time Frame: Day 2 and day 5/6 after oocyte pick up
|
Assessed by in vitro early embryo developmental competence of each punctured oocyte (Day 2 embryo morphology, ability to reach the blastocyst stage, Day 5/6 blastocyst morphology, blastocyst outcome (transfer, freezing, discarding)
|
Day 2 and day 5/6 after oocyte pick up
|
Embryo implantation success (pregnancy success)
Time Frame: From day 7 after embryo transfer for beta hCG assay, at 8 weeks of amenorrhea for foetus cardiac activity and after birth
|
Assessed by confirmation of a clinical pregnancy (blood beta human chorionic gonadotropin assay: > 1000 Unity Intenational /L), by confirmation of on-going pregnancy (ultrasound measure of foetus cardiac activity) and by confirmation delivery of live and healthy birth
|
From day 7 after embryo transfer for beta hCG assay, at 8 weeks of amenorrhea for foetus cardiac activity and after birth
|
Oxidative stress biomarkers in follicular fluid
Time Frame: baseline
|
Assessed by measure of antioxidant vitamins (carotenoids, vitamin E, retinol) by High Performance Liquid Chromatography
|
baseline
|
Oxidative stress biomarkers in follicular fluid
Time Frame: Baseline
|
Assessed by measure of oxidized lipids (isoprostanoids) by LC-MS/MS
|
Baseline
|
Oxidative stress biomarkers in follicular fluid
Time Frame: Baseline
|
Assessed by measure of antioxidant power (FRAP: Ferric ion Reducing Antioxidant Power) by spectrophotometry
|
Baseline
|
Oxidative stress biomarkers in follicular fluid
Time Frame: Baseline
|
Assessed by measure of glutathione peroxidase activity by spectrophometry
|
Baseline
|
Oxidative stress biomarkers in blood
Time Frame: On the eve of baseline
|
Assessed by measure of plasma antioxidant vitamins (carotenoids, vitamin E, retinol) by HPLC
|
On the eve of baseline
|
Oxidative stress biomarkers in blood
Time Frame: On the eve of baseline
|
Assessed by measure of plasma oxidized lipids (isoprostanoids) by LC-MS/M
|
On the eve of baseline
|
Oxidative stress biomarkers in blood
Time Frame: On the eve of baseline
|
Assessed by measure of plasma antioxidant power (FRAP) by spectrophotometry
|
On the eve of baseline
|
Oxidative stress biomarkers in blood
Time Frame: On the eve of baseline
|
Assessed by measure of activities of glutathione peroxidase, catalase and superoxide dismutase in red blood cells by UV and visible spectrophometry
|
On the eve of baseline
|
Oxidative stress biomarkers in urine
Time Frame: baseline
|
Assessed by measure of oxidized lipids (isoprostanoids) by LC-MS/MS
|
baseline
|
Information on woman lifestyles
Time Frame: The 3 last months of lifestyles before baseline
|
Assessed by a questionnaire on sociodemographic characteristics, smoking, physical activity, professional and environmental expositions, consumption of dietary supplements (antioxidants), consumption of drinks (tap water, from plastic bottle, cans...), food reheating habit, consumption of food from tin box, use of hygiene and cosmetic products...
|
The 3 last months of lifestyles before baseline
|
Pollutant effects on patient granulosa cells in vitro
Time Frame: after 24 or 48h of exposure
|
Assessed on cellular viability (CCK8, live-dead assay)
|
after 24 or 48h of exposure
|
Pollutant effects on patient granulosa cells in vitro
Time Frame: after 24 or 48h of exposure
|
Assessed on proliferation (BrdU)
|
after 24 or 48h of exposure
|
Pollutant effects on patient granulosa cells in vitro
Time Frame: after 48 or 72h of exposure
|
Assessed on steroid production (ELISA, LC-MS)
|
after 48 or 72h of exposure
|
Pollutant effects on patient granulosa cells in vitro
Time Frame: after 1 or 24h of exposure
|
Assessed on energetic metabolism (mitochondrial and glycolytic activities by Seahorse and Omnilog assays)
|
after 1 or 24h of exposure
|
Pollutant effects on patient granulosa cells in vitro
Time Frame: after 5, 6 or 24h of exposure
|
Assessed on oxidative stress biomarkers (reactive oxygen production, Nrf2 nuclear translocation by confocal microscopy, cytometry and fluorimetry)
|
after 5, 6 or 24h of exposure
|
Pollutant effects on patient granulosa cells in vitro
Time Frame: after 24, 48 or 72h of exposure
|
Assessed on protein expression (Western Blotting) of several markers of the studied functions (including oxidative stress)
|
after 24, 48 or 72h of exposure
|
Pollutant effects on patient granulosa cells in vitro
Time Frame: after 6 or 24h of exposure
|
Assessed on gene expression (RNAseq and Quantitative Reverse Transcription-PCR) of several markers of the studied functions (including oxidative stress)
|
after 6 or 24h of exposure
|
Pollutant effects on patient granulosa cells in vitro
Time Frame: after 1, 5, 10, 30 and 60 min of exposure
|
Assessed on protein expression (Western Blotting ) of signaling pathways
|
after 1, 5, 10, 30 and 60 min of exposure
|
Pollutant effects on patient granulosa cells in vitro
Time Frame: after 6h of exposure
|
Assessed on gene expression (RNAseq and qRT-PCR) of signaling pathways
|
after 6h of exposure
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Fabrice GUERIF, MD-PhD, University Hospital, Tours
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- DR200209
- 2020-A03241-38 (Other Identifier: IdRCB)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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