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AROPE : Early Ovarian Reserve Decreased : Impact of Exposure to Persistent Endocrine Disruptors and Organic Solvents (AROPE)

Primary Purpose

Female Infertility

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Self-administered questionnaire and blood and urine samples
Sponsored by
Rennes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Female Infertility focused on measuring Early ovarian reserve decreased

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria :

The cases will be:

  • women among couples consulting for infertility in 4 centers for medically assisted procreation (AMP) performing in vitro fertilization in the Brittany Pays de Loire region: the university hospital (CHU) of BREST, the CHU of RENNES, the La Sagesse clinic in RENNES and the CHU de NANTES,
  • having at least one characteristic of alteration of the ovarian reserve: a total number of antral follicles (left ovary + right ovary) less than 7 and / or a blood level of anti-Müllerian hormone (AMH) less than or equal to 1 , 1 ng / ml,
  • age between 18 and 40 years old,
  • with, in the event of past stimulation, at least one month since the last stimulation at the time of the blood and urine samples,
  • having signed a free and informed consent.

For each case, two controls will be included with a pairing on the center and on the age group of 5 years (frequency pairing). It will be :

  • women among couples consulting for infertility in 4 centers for medically assisted procreation (AMP) performing in vitro fertilization in the Brittany Pays de Loire region: the university hospital (CHU) of BREST, the CHU of RENNES, the La Sagesse clinic in RENNES and the CHU de NANTES,
  • whose infertility assessment is strictly normal (AMH between 1.5 and 5 ng / ml, without genital malformation and with a menstrual cycle between 26 and 35 days),
  • age between 18 and 40 years old,
  • with, in the event of past stimulation, at least one month since the last stimulation at the time of the blood and urine samples,
  • having signed a free and informed consent.

The non-inclusion criteria for cases and witnesses will be:

  • ovarian endometriosis,
  • polycystic ovary syndrome,
  • a history of adnexal surgery,
  • a history of cancer with chemotherapy or radiotherapy,
  • morbid obesity (BMI ≥ 35 kg / m²),
  • a chromosomal genetic syndrome (Turner and Fragile X)
  • adults who are the subject of legal protection (safeguard of justice, curatorship, guardianship) and persons deprived of their liberty.

Sites / Locations

  • Brest university hospital
  • Nantes university hospital
  • Cabinet de Gynécologie Malakoff
  • Clinique Mutualiste de La Sagesse
  • Rennes university hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Cases

Controls

Arm Description

Cases and controls will benefit, as usual in France concerning infertility etiology examinations, of a follicle antral count by transvaginal ultrasound and AMH measurement. At baseline, physicians will complete a short questionnaire to check the inclusion criterion, the results of the measurement of follicle count and hormone measurement (including AMH). Cases and controls will respond to self-administered questionnaire at inclusion with information about their medical history, their demographics, their tobacco and alcohol consumption, their occupation and products handled in the workplace. Blood samples (for measure of persistent organic pollutants and heavy metals) and urine (for measure of metabolites of glycol ethers) will be collect at baseline. Occupational exposures to solvents will be defined using job exposures matrices. The risk of decreased ovarian reserve will be analyzed using logistic regressions for each exposure of interest adjusting for potential confounders.

Cases and controls will benefit, as usual in France concerning infertility etiology examinations, of a follicle antral count by transvaginal ultrasound and AMH measurement. At baseline, physicians will complete a short questionnaire to check the inclusion criterion, the results of the measurement of follicle count and hormone measurement (including AMH). Cases and controls will respond to self-administered questionnaire at inclusion with information about their medical history, their demographics, their tobacco and alcohol consumption, their occupation and products handled in the workplace. Blood samples (for measure of persistent organic pollutants and heavy metals) and urine (for measure of metabolites of glycol ethers) will be collect at baseline. Occupational exposures to solvents will be defined using job exposures matrices. The risk of decreased ovarian reserve will be analyzed using logistic regressions for each exposure of interest adjusting for potential confounders.

Outcomes

Primary Outcome Measures

Persistant organic pollutants dosage
Persistant organic pollutants levels

Secondary Outcome Measures

Organic solvents dosage
Occupational exposure to organic solvents
Glycol ethers métabolites dosage
Occupational exposure to glycol ethers metabolites.
Heavy metals dosage
Occupational exposure to heavy metals.

Full Information

First Posted
May 17, 2016
Last Updated
May 22, 2023
Sponsor
Rennes University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02802397
Brief Title
AROPE : Early Ovarian Reserve Decreased : Impact of Exposure to Persistent Endocrine Disruptors and Organic Solvents
Acronym
AROPE
Official Title
AROPE : Early Ovarian Reserve Decreased : Impact of Exposure to Persistent Endocrine Disruptors and Organic Solvents
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
December 6, 2016 (Actual)
Primary Completion Date
February 6, 2020 (Actual)
Study Completion Date
November 2, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rennes University Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Early ovarian reserve decreased is one of the main causes of infertility for women after 35 years. The relationship between this decreased and exposure to chemicals, including persistent endocrine disruptors or organic solvents, has been little studied. However, several in vivo or in vitro experimental studies suggested that these chemicals may impaired ovarian function. The main objective is to study the relationship between early ovarian reserve decreased and exposure to persistent organic pollutants. The secondary objectives are to study the relationship between early ovarian reserve decreased and exposure to organic solvents and heavy metals. Multicenter case-control study. This project will permit to increase the knowledge concerning the etiology of early decreased ovarian reserve. Considering that exposure of interest are frequent, the results may be important in a public health perspective. If associations are observed in this study, the results may encouraged prevention strategy.
Detailed Description
Cases and controls will benefit, as usual in France concerning infertility etiology examinations, of a follicle antral count by transvaginal ultrasound and AMH measurement. At baseline, physicians will complete a short questionnaire to check the inclusion criterion, the results of the measurement of follicle count and hormone measurement (including AMH). Cases and controls will respond to self-administered questionnaire at inclusion with information about their medical history, their demographics, their tobacco and alcohol consumption, their occupation and products handled in the workplace. Blood samples (for measure of persistent organic pollutants and heavy metals) and urine (for measure of metabolites of glycol ethers) will be collect at baseline. Occupational exposures to solvents will be defined using job exposures matrices. The risk of decreased ovarian reserve will be analyzed using logistic regressions for each exposure of interest adjusting for potential confounders.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Female Infertility
Keywords
Early ovarian reserve decreased

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
335 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cases
Arm Type
Other
Arm Description
Cases and controls will benefit, as usual in France concerning infertility etiology examinations, of a follicle antral count by transvaginal ultrasound and AMH measurement. At baseline, physicians will complete a short questionnaire to check the inclusion criterion, the results of the measurement of follicle count and hormone measurement (including AMH). Cases and controls will respond to self-administered questionnaire at inclusion with information about their medical history, their demographics, their tobacco and alcohol consumption, their occupation and products handled in the workplace. Blood samples (for measure of persistent organic pollutants and heavy metals) and urine (for measure of metabolites of glycol ethers) will be collect at baseline. Occupational exposures to solvents will be defined using job exposures matrices. The risk of decreased ovarian reserve will be analyzed using logistic regressions for each exposure of interest adjusting for potential confounders.
Arm Title
Controls
Arm Type
Other
Arm Description
Cases and controls will benefit, as usual in France concerning infertility etiology examinations, of a follicle antral count by transvaginal ultrasound and AMH measurement. At baseline, physicians will complete a short questionnaire to check the inclusion criterion, the results of the measurement of follicle count and hormone measurement (including AMH). Cases and controls will respond to self-administered questionnaire at inclusion with information about their medical history, their demographics, their tobacco and alcohol consumption, their occupation and products handled in the workplace. Blood samples (for measure of persistent organic pollutants and heavy metals) and urine (for measure of metabolites of glycol ethers) will be collect at baseline. Occupational exposures to solvents will be defined using job exposures matrices. The risk of decreased ovarian reserve will be analyzed using logistic regressions for each exposure of interest adjusting for potential confounders.
Intervention Type
Other
Intervention Name(s)
Self-administered questionnaire and blood and urine samples
Intervention Description
Self-administered questionnaire and blood and urine samples
Primary Outcome Measure Information:
Title
Persistant organic pollutants dosage
Description
Persistant organic pollutants levels
Time Frame
Day 1
Secondary Outcome Measure Information:
Title
Organic solvents dosage
Description
Occupational exposure to organic solvents
Time Frame
Day 1
Title
Glycol ethers métabolites dosage
Description
Occupational exposure to glycol ethers metabolites.
Time Frame
Day 1
Title
Heavy metals dosage
Description
Occupational exposure to heavy metals.
Time Frame
Day 1

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria : The cases will be: women among couples consulting for infertility in 4 centers for medically assisted procreation (AMP) performing in vitro fertilization in the Brittany Pays de Loire region: the university hospital (CHU) of BREST, the CHU of RENNES, the La Sagesse clinic in RENNES and the CHU de NANTES, having at least one characteristic of alteration of the ovarian reserve: a total number of antral follicles (left ovary + right ovary) less than 7 and / or a blood level of anti-Müllerian hormone (AMH) less than or equal to 1 , 1 ng / ml, age between 18 and 40 years old, with, in the event of past stimulation, at least one month since the last stimulation at the time of the blood and urine samples, having signed a free and informed consent. For each case, two controls will be included with a pairing on the center and on the age group of 5 years (frequency pairing). It will be : women among couples consulting for infertility in 4 centers for medically assisted procreation (AMP) performing in vitro fertilization in the Brittany Pays de Loire region: the university hospital (CHU) of BREST, the CHU of RENNES, the La Sagesse clinic in RENNES and the CHU de NANTES, whose infertility assessment is strictly normal (AMH between 1.5 and 5 ng / ml, without genital malformation and with a menstrual cycle between 26 and 35 days), age between 18 and 40 years old, with, in the event of past stimulation, at least one month since the last stimulation at the time of the blood and urine samples, having signed a free and informed consent. The non-inclusion criteria for cases and witnesses will be: ovarian endometriosis, polycystic ovary syndrome, a history of adnexal surgery, a history of cancer with chemotherapy or radiotherapy, morbid obesity (BMI ≥ 35 kg / m²), a chromosomal genetic syndrome (Turner and Fragile X) adults who are the subject of legal protection (safeguard of justice, curatorship, guardianship) and persons deprived of their liberty.
Facility Information:
Facility Name
Brest university hospital
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
Nantes university hospital
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Cabinet de Gynécologie Malakoff
City
Rennes
ZIP/Postal Code
35000
Country
France
Facility Name
Clinique Mutualiste de La Sagesse
City
Rennes
ZIP/Postal Code
35000
Country
France
Facility Name
Rennes university hospital
City
Rennes
ZIP/Postal Code
35200
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
36881900
Citation
Genard-Walton M, Warembourg C, Duros S, Mercier F, Lefebvre T, Guivarc'h-Leveque A, Le Martelot MT, Le Bot B, Jacquemin B, Chevrier C, Cordier S, Costet N, Multigner L, Garlantezec R. Serum persistent organic pollutants and diminished ovarian reserve: a single-exposure and mixture exposure approach from a French case-control study. Hum Reprod. 2023 Apr 3;38(4):701-715. doi: 10.1093/humrep/dead028.
Results Reference
result

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AROPE : Early Ovarian Reserve Decreased : Impact of Exposure to Persistent Endocrine Disruptors and Organic Solvents

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