Clinical trial NCT04820985: Analysis of the Composition of the Vaginal Microbiota During IVF Treatment and Correlation With Serum Progesterone Level on the Day of Embryo Transfer
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: IVF
Keywords: Pregnancy
vaginal microbiota
Progesterone
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2021-03-29
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Class of vaginal flora according to community state type
timeFrame: 3 Months before ovarian stimulation
measure: Microbiota richness of vaginal flora
timeFrame: 3 Months before ovarian stimulation
measure: Microbiota alpha diversity of vaginal flora
timeFrame: 3 Months before ovarian stimulation
measure: Microbiota beta diversity of vaginal flora
timeFrame: 3 Months before ovarian stimulation
measure: Plasma progesterone level on the day of embryo transfer
timeFrame: Day of embryo transfer (Day 0)
Secondary outcomes:
measure: Class of vaginal flora according to community state type
timeFrame: Day of oocyte puncture (Month 3)
measure: Class of vaginal flora according to community state type
timeFrame: Day of embryo transfer (Day 93)
measure: Class of vaginal flora according to community state type
timeFrame: Day of beta-human chorionic gonadotropin dosage (Day 108)
measure: Microbiota richness of vaginal flora
timeFrame: Day of oocyte puncture (Month 3)
measure: Microbiota richness of vaginal flora
timeFrame: Day of embryo transfer (Day 93)
measure: Microbiota richness of vaginal flora
timeFrame: Day of beta-human chorionic gonadotropin dosage (Day 108)
measure: Microbiota alpha diversity of vaginal flora
timeFrame: Day of oocyte puncture (Month 3)
measure: Microbiota alpha diversity of vaginal flora
timeFrame: Day of embryo transfer (Day 93)
measure: Microbiota alpha diversity of vaginal flora
timeFrame: Day of beta-human chorionic gonadotropin dosage (Day 108)
measure: Microbiota beta diversity of vaginal flora
timeFrame: Day of oocyte puncture (Month 3)
measure: Microbiota beta diversity of vaginal flora
timeFrame: Day of embryo transfer (Day 93)
measure: Microbiota beta diversity of vaginal flora
timeFrame: Day of beta-human chorionic gonadotropin dosage (Day 108)
measure: Pregnancy success
timeFrame: Month 3
measure: Pregnancy progression
timeFrame: Month 3
measure: Treatments received for IVF
timeFrame: Month 3
measure: Plasma progesterone level
timeFrame: Month 3
Other outcomes:
Locations:
city: Nîmes
country: France
facility: CHU de Nimes
Study officials:
affiliation: CHU de Nimes
name: Stéphanie Huberlant
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.