The FLORA-project: in Search for the Microbial Cause of Chronic Endometritis and the Most Appropriate Treatment to Obtain a Successful Pregnancy IVF/ICSI

NCT05337072 | Unknown

• 1 other identifier: FLORA-project
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic endometritis is an inflammatory condition of the endometrium. This inflammation can negatively affect fertility and pregnancy. The pathology is frequently (+-10%) observed in women with fertility problems. Today, diagnosis of chronic endometritis is not evident, since no well-validated classification scales are available. In the UZ Brussel the pathology department applies its own in-house scoring system, based on the presence and position of plasma cells within the histological images. Despite limited research so far, it recently became clear that the endometrium is colonized by micro-organisms (the microbiome). However, it is still unclear what role these microorganisms play in chronic endometritis and fertility problems. Chronic endometritis is often diagnosed in the context of fertility problems, and the patient is treated 'blindly' with broad-spectrum antibiotics such as doxycycline. Broad-spectrum antibiotics unnecessarily eradicate many microorganisms in our body, including the ones that positively influence implantation. The exact cause of chronic endometritis is unknown, so treatment remains empirical. The research and knowledge in the endometrial microbiome is constantly expanding, mainly due to the rise of research into the links between pathologies and human microbiota. It is becoming increasingly clear that the composition of the microbiome can play a vital role in health and disease. Regarding the influence of the endometrial microbiome on different pathologies, such as chronic endometritis and implantation failure or miscarriage, there is still no consensus. Despite multiple studies on the endometrial microbiome, we are not yet able to define a normal or healthy endometrial microbiome. In this project, we want to gain insight into the microorganisms that are present in the female reproductive tract based on various techniques. The analyses will performed on an endometrial biopsy and a vaginal swab. The biopsy is routinely taken at Brussels IVF for the detection of plasma cells in the anatomopathology lab for the diagnosis of chronic endometritis. In the microbiology lab we will investigate which microorganisms are present in the female reproductive tract with and without the histological diagnosis of chronic endometritis. This will be done based on the state-of-the-art analytical techniques metagenomics (sequencing) and culturomics (culture).

Conditions

Endometritis; Chronic; Subfertility

Keywords

Microbiome

Outcome Measures

Primary Outcomes (1)

• Microbiome analysis through sequencing and culture

  The vaginal and endometrial microbiome will be evaluated through metagenomics sequencing and high-troughput culturomics. Metagenomics: An amplicon sequencing technique will be applied. Deep-sequencing metagenomic analysis will be performed. Microbiome bioinformatics and statistical data analyses will be performed through Quantitative Insights Into Microbial Ecology - QIIME2®. Community composition, biodiversity, and statistically different abundant taxa will be identified using appropriate statistical models, and visualisation methods. Culturomics: Two different pre-incubation conditions will be applied. We enrich both an aerobic and an anaerobic bloodculture bottle with sterile rumen fluid, sterile defibrinated sheep blood and a homemade supplement mix. Eight different agar plates will be used. After five days of incubation, all different bacterial and fungal colonies will be isolated for MALDI-TOF MS or 16S rRNA sequencing.

  2 years

Interventions

Microbiome study DIAGNOSTIC_TEST

Investigation of the vaginal and endometrial microbiome

Eligibility Criteria

• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

We will include women planned for IVF/ICSI treatment at Brussels IVF (UZ Brussel) who undergo a diagnostic hysteroscopy in preparation of their treatment.

You may qualify if:

• Women planned for IVF/ICSI treatment at Brussels IVF (UZ Brussel)
• Women who undergo a diagnostic hysteroscopy in preparation of their treatment

You may not qualify if:

• If an interventional instead of a diagnostic hysteroscopy in planned
• In the occurence If a previous history of chronic endometritis and the use of antibiotics in the last 3 months.

Sponsors & Collaborators

• Universitair Ziekenhuis Brussel: lead

Study Sites (1)

Universitair Ziekenhuis Brussel

Brussels, 1090, Belgium

Location

Related Links

• Related Info

Biospecimen

Retention: SAMPLES WITH DNA

Vaginal swab Endometrial biopsy

MeSH Terms

Conditions

Endometritis; Bronchiolitis Obliterans Syndrome; Infertility

Condition Hierarchy (Ancestors)

Pelvic Inflammatory Disease; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Uterine Diseases; Genital Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Microbiologist

Study Record Dates

• First Submitted: April 6, 2022
• First Posted: April 20, 2022
• Study Start: May 1, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: March 28, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)