Diagnosis of Chronic Endometritis in Endometrial Fluid Using Molecular Techniques to Improve the Outcomes of Assisted Reproductive Treatments

NCT03169621 | Terminated

• 1 other identifier: IGX1-ECR-CS-17-01
• Study Type: observational
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic endometritis (CE) is a persistent inflammation of the endometrial lining caused by the infection of the uterine cavity mainly by bacterial pathogens. It is known that CE can produce implantation failure, recurrent abortion and preterm labor. The study hypothesis is that patients who have repeated implantation failures (RIF) despite transferring good quality and normal embryos, diagnosed by preimplantation Genetic Diagnosis (PGD), into a receptive endometrium, diagnosed by Endometrial Receptivity Analysis (ERA), may present asymptomatic CE, being the altered endometrium the main cause of these implantation failures. The current diagnosis of CE is the microbiological culture of endometrial biopsy samples. Alternatively, examination of the uterine cavity by hysteroscopy is effective at 93.4%. However, both methods have limitations, such as the time needed to obtain the diagnosis, the economic cost of the tests, the possibility of detecting microorganisms in culture etc. For these reasons, the developing of a simple, fast, cheap and minimally invasive diagnostic tool for CE patients subjected to IVF treatments is expected. It would be very useful in order to establish a specific treatment and improve pregnancy rates in infertile patients. For this reason, the bacterial DNA present in the endometrial fluid samples will be obtained and the identification of the causative pathogens of CE will be done by sequencing (NGS) and/or quantitative PCR with specific oligonucleotides for the most common bacteria causing CE. The validation of this new method will be performed by comparison with the microbiological diagnosis of those same patients.

Conditions

Chronic Endometritis

Keywords

Chronic Endometritis; Endometrial pathogens; Microbiological diagnosis; Next Generation Sequencing; Metagenomics; Endometrial receptivity

Outcome Measures

Primary Outcomes (1)

• Developing of a new non invasive diagnosis test by Next Generation Sequencing (NGS) analysis for patients diagnosed with chronic endometritis (CE).

  DNA analysis by NGS using endometrial fluid for the CE diagnose.

  24 months

Secondary Outcomes (6)

• To compare the diagnose of CE, determined by classical and molecular methods measured by NGS, in both types of samples analyzed (endometrial fluid and endometrial biopsy).

  24 months

• Qualitative study of the endometrial microbiome by classical and molecular methods in order to determine their influence in the CE diagnose.

  24 months

• Quantitative study of the endometrial microbiome by classical and molecular methods in order to determine their influence in the CE diagnose.

  24 months

• Relationship between the implantation rate and the diagnosis of CE, by molecular and classical methods, in patients undergoing assisted reproduction treatments (ART).

  6 weeks

• Relationship between the ongoing pregnancy rate per embryo transfer and the diagnosis of CE, by molecular and classical methods, in patients undergoing assisted reproduction treatments (ART).

  5 months

Study Arms (1)

Patients with RIF

Patients with repeated implantation failure (RIF) with indication of hysteroscopy within normal clinical practice, who will undergo FIV or ICSI and embryo transfer within their assisted reproduction treatment (ART).

Procedure: Endometrial Biopsy and endometrial fluid collection

Interventions

Endometrial Biopsy and endometrial fluid collection PROCEDURE

On day 5 of the Hormonal Replacement Therapy (after 5 days of progesterone administration), the doctor will perform endometrial fluid aspiration (EF) followed by an endometrial biopsy (EB) the same day of hysteroscopy that is performed as usual clinical practice. EF sample will be analyzed by molecular techniques (Next Generation Sequencing) for the detection of infectious agents and the EB sample will be divided into three parts, one of them will be used for molecular analysis (as control of the bacterial content present in the EF) and the others will be used for microbiological analysis and histological techniques respectively. The Assisted Reproductive Treatment (ART) will be performed once the specialist considers it appropriated according to the clinical standard practice and the reproductive rates will be correlated with the diagnosis of CE comparing the results of ART before and after its diagnosis of CE.

Patients with RIF

Eligibility Criteria

• Age: 18 Years - 38 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients with repeated implantation failure with indication of hysteroscopy within normal clinical practice, who will undergo FIV or ICSI and embryo transfer within their assisted reproduction treatment at our center (Hospital Clínico Universitario de Valencia) .

You may qualify if:

• Patients who provide their written informed consent after having been informed of the all study aspects.
• IVF or ICSI cycles with own oocytes, with blastocyst transfer (day 5 or 6 of stage development).
• Women with age comprised between 18 and 38 years (both included).
• Body mass index: 18.5 - 30 km/m2 (both included)
• Adequate ovarian reserve \> 8 antral follicles (RFA) and/or Antimüllerian hormone (HAM)\> 1 ng / mL.
• Concentration of spermatozoa \> 2 million sperm/ml.

You may not qualify if:

• Congenital or acquired uterine pathologies.
• Endometriosis.
• Patients with IUDs in the last 3 months.
• Patients who have taken prescribed antibiotic treatment in the last 3 months.
• Any disease or medical condition that could be unstable or could endanger the security of the patient and her compliance in the study.

Sponsors & Collaborators

• Igenomix: lead
• Instituto de Investigacion Sanitaria INCLIVA: collaborator
• University of Valencia: collaborator

Study Sites (1)

Hospital Clínic Universitari de Valencia - INCLIVA

Valencia, 46010, Spain

Location

Biospecimen

Retention: SAMPLES WITH DNA

DNA will be analyzed in the endometrial fluid. These samples will be completely exhausted during the analysis.

Study Officials

• Carlos Simón, MD PhD

  Igenomix

  STUDY CHAIR

• Gemma Arribas, MD PhD

  Hospital Clínic Universitari

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2017
• First Posted: May 30, 2017
• Study Start: April 27, 2017
• Primary Completion: June 26, 2018
• Study Completion: February 13, 2019
• Last Updated: March 26, 2019

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)