Clinical trial NCT04866329: Female Fertility, Environmental Agents and Stress Oxidant
Official title: FERTilité féminine, Agents ENvironnementaux et Stress OXydant
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Female Infertility
Keywords: Environmental pollutants
Bisphenols
Ethynylestradiol
Glyphosate
Oxidative stress
Oocyte and embryo quality
In vitro fertilization
Pregnancy
Follicular fluid and urine biomarkers
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2021-04-29
Enrollment: 500
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 43
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women followed in the department for an in vitro fertilisation procedure

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Presence or absence of ethinylestradiol in follicular fluid
timeFrame: Baseline
measure: Presence or absence of ethinylestradiol in urine
timeFrame: Baseline
measure: Presence or absence of bisphenols in follicular fluid
timeFrame: Baseline
measure: Presence or absence of bisphenols in urine
timeFrame: Baseline
measure: Presence or absence of glyphosate in follicular fluid
timeFrame: baseline
measure: Presence or absence of glyphosate in urine
timeFrame: baseline
measure: Concentration of ethinylestradiol in follicular fluid
timeFrame: baseline
measure: Concentration of ethinylestradiol in urine
timeFrame: baseline
measure: Concentration of bisphenols in follicular fluid
timeFrame: baseline
measure: Concentration of bisphenols in urine
timeFrame: baseline
measure: Concentration of glyphosate in follicular fluid
timeFrame: baseline
measure: Concentration of glyphosate in urine
timeFrame: baseline
Secondary outcomes:
measure: Oocyte quality
timeFrame: baseline
measure: Embryo quality
timeFrame: Day 2 and day 5/6 after oocyte pick up
measure: Embryo implantation success (pregnancy success)
timeFrame: From day 7 after embryo transfer for beta hCG assay, at 8 weeks of amenorrhea for foetus cardiac activity and after birth
measure: Oxidative stress biomarkers in follicular fluid
timeFrame: baseline
measure: Oxidative stress biomarkers in follicular fluid
timeFrame: Baseline
measure: Oxidative stress biomarkers in follicular fluid
timeFrame: Baseline
measure: Oxidative stress biomarkers in follicular fluid
timeFrame: Baseline
measure: Oxidative stress biomarkers in blood
timeFrame: On the eve of baseline
measure: Oxidative stress biomarkers in blood
timeFrame: On the eve of baseline
measure: Oxidative stress biomarkers in blood
timeFrame: On the eve of baseline
measure: Oxidative stress biomarkers in blood
timeFrame: On the eve of baseline
measure: Oxidative stress biomarkers in urine
timeFrame: baseline
measure: Information on woman lifestyles
timeFrame: The 3 last months of lifestyles before baseline
measure: Pollutant effects on patient granulosa cells in vitro
timeFrame: after 24 or 48h of exposure
measure: Pollutant effects on patient granulosa cells in vitro
timeFrame: after 24 or 48h of exposure
measure: Pollutant effects on patient granulosa cells in vitro
timeFrame: after 48 or 72h of exposure
measure: Pollutant effects on patient granulosa cells in vitro
timeFrame: after 1 or 24h of exposure
measure: Pollutant effects on patient granulosa cells in vitro
timeFrame: after 5, 6 or 24h of exposure
measure: Pollutant effects on patient granulosa cells in vitro
timeFrame: after 24, 48 or 72h of exposure
measure: Pollutant effects on patient granulosa cells in vitro
timeFrame: after 6 or 24h of exposure
measure: Pollutant effects on patient granulosa cells in vitro
timeFrame: after 1, 5, 10, 30 and 60 min of exposure
measure: Pollutant effects on patient granulosa cells in vitro
timeFrame: after 6h of exposure
Other outcomes:
Locations:
city: Tours
country: France
facility: Department of Reproductive Medicine and Biology, Univesity Hospital, Tours
Study officials:
affiliation: University Hospital, Tours
name: Fabrice GUERIF, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References: