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

Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexFemale
AgeNot listed
SponsorUniversitair Ziekenhuis Brussel

About this trial

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 a transvaginal ultrasound, endometrial biopsies which will be harvested during (guided biopsy) and after (blind pipelle biopsy) the hysteroscopy 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).

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Women planned for IVF/ICSI treatment at Brussels IVF (UZ Brussel)

Women who undergo a diagnostic hysteroscopy in preparation of their treatment

Disqualifiers

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.

Trial 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.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • Microbiome study

    Diagnostic test

    Investigation of the vaginal and endometrial microbiome

Treatment groups

No treatment groups listed

Trial outcomes

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.

Time frame
2 years

Secondary outcomes

Other outcomes

Sponsors and contacts

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