Analysis of the Composition of the Vaginal Microbiota During IVF Treatment and Correlation With Serum Progesterone Level on the Day of Embryo Transfer (MICROFIV)

Analyse de la Composition du Microbiote Vaginal à différents Temps de la Prise en Charge en FIV et corrélation Avec le Taux de progestérone sérique le Jour du Transfert d'Embryon

The composition of the vaginal microbiota varies throughout a woman's life and is sensitive to hormonal and environmental factors. Specifically, hormonal treatments necessary in the medically assisted procreation (MAP) processes can influence the vaginal microbiota. New sequencing techniques have been used to characterize the vaginal microbiota, demonstrating that the microbiota could be divided into 5 classes. The composition of the vaginal microbiota seems to have an implication in the evolution of a pregnancy after IVF. It is therefore essential to have more data on the evolution of the vaginal microbiota at the different stages of IVF treatment and to analyze whether this evolution can be predictive of the success of embryo implantation. Good endometrial progesterone impregnation is an essential prerequisite for ensuring embryo implantation. Indeed, supporting the luteal phase through vaginal progesterone is an essential step in IVF protocols to ensure synchronization between endometrial maturation and embryonic age. However, the serum progesterone level on the day of embryo transfer varies widely between patients. Several factors such as age, vaginal mucosa trophicity, estrogen impregnation and sexual activity are known to affect the vaginal absorption of progesterone. The treatments and vaginal examinations performed during the IVF procedure could also have an impact on the constitution of the vaginal microbiota. The hypothesis of this research is that there is an alteration in the vaginal microbiota during the IVF process which may alter the absorption of vaginal progesterone, with an impact on the failure or success of embryo implantation.

Study Overview

• Status: Completed
• Conditions: IVF
• Intervention / Treatment: Other: Vaginal swab; Other: Blood test

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• France
  • Nîmes, France, 30029
    • CHU de Nîmes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 18 to 40 inclusive, Round1 or 2 of IVF or IVF-ICSI with fresh embryo transfer, without taking antibiotics in the 3 months preceding the first sample treated in the AMP center of the CHU de Nîmes.

Description

Inclusion Criteria:

• Patient in round 1 or 2 of IVF or IVF-ICSI with transfer of a fresh embryo with a normal preimplantation assessment, without antibiotic treatment in the 3 months preceding the sample.
• The patient must have given their free and informed consent and signed the consent form
• The patient must be a member or beneficiary of a health insurance plan

Exclusion Criteria:

• Use of antibiotics in the 3 months preceding the sample.
• Patient presenting an anomaly in the implantation assessment.
• Presence of uterine malformation, hydrosalpinx, chronic vaginosis.
• Patient undergoing a protocol to study endometrial receptivity.
• Patient of African American, African or Latin American origin (patients born to two parents of Hispanic origin) as people of African and Hispanic origin have a type IV flora vs people of Caucasian origins who have type I, II, III and V of the Ravel classification .
• Cancellation of the procedure for various reasons (stimulation failure, collection failure, fertilization failure or embryonic segmentation).
• Patient taking a freeze-all approach (freezing of the embryos) for various causes (risk of ovarian hyperstimulation, increase in progesterone, too thin endometrium, etc.).
• The subject is participating in a category 1 interventional study, or is in a period of exclusion determined by a previous study
• The subject refuses to sign the consent
• It is impossible to give the subject informed information
• The patient is under safeguard of justice or state guardianship

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Women undergoing IVF	Other: Vaginal swab; Vaginal flora swab 3 months before stimulation, at oocyte puncture, embryo transfer and beta-human chorionic gonadotropin dosing; Other: Blood test; Blood sample to measure plasma dose of progesterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Class of vaginal flora according to community state type	Classified into 5 classes of vaginal flora described according to Smith & Ravel 2017	3 Months before ovarian stimulation
Microbiota richness of vaginal flora	Measured by operational taxonomic unit	3 Months before ovarian stimulation
Microbiota alpha diversity of vaginal flora	Shannon Index	3 Months before ovarian stimulation
Microbiota beta diversity of vaginal flora	Bray Curtis index	3 Months before ovarian stimulation
Plasma progesterone level on the day of embryo transfer	Measured by chemiluminescence (nmol/L)	Day of embryo transfer (Day 0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Class of vaginal flora according to community state type	Classified into 5 classes of vaginal flora described according to Smith & Ravel 2017	Day of oocyte puncture (Month 3)
Class of vaginal flora according to community state type	Classified into 5 classes of vaginal flora described according to Smith & Ravel 2017	Day of embryo transfer (Day 93)
Class of vaginal flora according to community state type	Classified into 5 classes of vaginal flora described according to Smith & Ravel 2017	Day of beta-human chorionic gonadotropin dosage (Day 108)
Microbiota richness of vaginal flora	Measured by operational taxonomic unit	Day of oocyte puncture (Month 3)
Microbiota richness of vaginal flora	Measured by operational taxonomic unit	Day of embryo transfer (Day 93)
Microbiota richness of vaginal flora	Measured by operational taxonomic unit	Day of beta-human chorionic gonadotropin dosage (Day 108)
Microbiota alpha diversity of vaginal flora	Shannon Index	Day of oocyte puncture (Month 3)
Microbiota alpha diversity of vaginal flora	Shannon Index	Day of embryo transfer (Day 93)
Microbiota alpha diversity of vaginal flora	Shannon Index	Day of beta-human chorionic gonadotropin dosage (Day 108)
Microbiota beta diversity of vaginal flora	Bray Curtis index	Day of oocyte puncture (Month 3)
Microbiota beta diversity of vaginal flora	Bray Curtis index	Day of embryo transfer (Day 93)
Microbiota beta diversity of vaginal flora	Bray Curtis index	Day of beta-human chorionic gonadotropin dosage (Day 108)
Pregnancy success	Yes/No	Month 3
Pregnancy progression	Implantation failure/progression/miscarriage	Month 3
Treatments received for IVF	Description of treatments, taken from patient file	Month 3
Plasma progesterone level	Measured by chemiluminescence (nmol/L)	Month 3

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Stéphanie Huberlant, CHU de Nîmes

Publications and helpful links

General Publications

• Smith SB, Ravel J. The vaginal microbiota, host defence and reproductive physiology. J Physiol. 2017 Jan 15;595(2):451-463. doi: 10.1113/JP271694. Epub 2016 May 5.

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2021
• Primary Completion (Actual): January 11, 2023
• Study Completion (Actual): April 22, 2024

Study Registration Dates

• First Submitted: March 25, 2021
• First Submitted That Met QC Criteria: March 25, 2021
• First Posted (Actual): March 29, 2021

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Pregnancy; Progesterone; vaginal microbiota
• Other Study ID Numbers: NIMAO/2020-01/SH-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No