Chronic EndometritisChEndometritisNCT03169621
Diagnosis of Chronic Endometritis in Endometrial Fluid Using Molecular Techniques to Improve the Outcomes of Assisted Reproductive Treatments
An observational study of Chronic Endometritis, run by Igenomix at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 38 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Chronic Endometritis
- What is being tested?
- Endometrial Biopsy and endometrial fluid collection
- Type of treatment
- Surgery or procedure
- How many people
- 5 participants
- Where
- 1 siteSpain
- Study dates
- 27 Apr 2017to 13 Feb 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 38 years
- Women only
- Healthy volunteers accepted
- Adult
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) .
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
On day 5 of the Hormonal Replacement Therapy (after 5 days of progesterone administration), coinciding with the day of hysteroscopy indicated by the physician according to the routine clinical practice, samples of endometrial fluid (EF) and endometrial biopsy (EB) of patients with RIF will be obtained. These samples will be used for the diagnosis of CE by both classic and molecular methods. Specifically, EF sample will be analyzed by molecular techniques using Next Generation Sequencing (NGS) for the detection of infectious agents. 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), another part will be subjected to microbiological analysis and the third part will be analyzed using histological techniques. In this way, comparisons will be made between the different diagnostic methods of CE in the two sample types (EF and EB) and the efficacy values of the new diagnostic test (sensitivity, specificity, positive and negative predictive values and Receiving Operating Characteristic curves) will be obtained using the microbiological diagnosis as a reference (gold standard method).
Patients with a negative outcome for CE (approximately 40%) will continue with the expected assisted reproduction treatment (ART) according to the clinic's standard protocol and patients with a positive outcome for CE (approx. 60%) will receive antibiotic treatment according to usual clinical practice (time and type of antibiotic will be different according to the microbiological diagnosis). Once this treatment is completed, the improvement of these patients will be confirmed obtaining a second sample of EF and EB. The Assisted Reproductive Treatment (ART) will be performed once the specialist considers it appropriated.
Finally, reproductive rates will be correlated with the diagnosis of CE. Therefore, an observational analytical study, in which a comparison of the ART results before and after its diagnosis of CE, will be carried out. The reproductive impact of an altered endometrial microbiota will be assessed analyzing the implantation rates, pregnancy and ongoing pregnancy.
- Conditions
- Chronic Endometritis
- Being tested
- Endometrial Biopsy and endometrial fluid collection
- Keywords
- Chronic Endometritis, Endometrial pathogens, Microbiological diagnosis, Next Generation Sequencing, Metagenomics, Endometrial receptivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endometrial Biopsy and endometrial fluid collectionProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Procedure: Endometrial Biopsy and endometrial fluid collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Endometrial fluid will be used for the DNA analysis by NGS and endometrial biopsy will be used for the classical diagnosis ((microbial culture, histology and hysteroscopy).
Measured: 24 months
Qualitative study of the endometrial microbiome by classical and molecular methods in order to determine their influence in the CE diagnose.
To determine the identity of pathogenic bacteria measured by NGS that could establish endometrial infection.
Measured: 24 months
Quantitative study of the endometrial microbiome by classical and molecular methods in order to determine their influence in the CE diagnose.
To determine the minimal amount of pathogenic bacteria measured by NGS that could establish endometrial infection.
Measured: 24 months
Relationship between the implantation rate and the diagnosis of CE, by molecular and classical methods, in patients undergoing assisted reproduction treatments (ART).
Implantation rate is defined as the number of gestational sacs observed by vaginal ultrasound per number of transferred embryos in the 6th gestational week.
Measured: 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).
Ongoing pregnancy rate is defined as the number of ongoing pregnancies after the 20th gestational week per total number of embryo transfers performed.
Measured: 5 months
Relationship between the live birth rate and the diagnosis of CE, by molecular and classical methods, in patients undergoing assisted reproduction treatments (ART).
Live birth rate is defined as the number of the total live births per total number of embryo transfers performed.
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2017
- Study start27 Apr 2017
- Primary completion26 Jun 2018
- Study completion13 Feb 2019
Why it stopped: Low patient enrolment during the recruiting period
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic EndometritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Igenomix
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Instituto de Investigacion Sanitaria INCLIVA, University of Valencia
- Responsible party
- Sponsor
- Investigators
- Carlos Simón, MD PhD, Study chair, IgenomixGemma Arribas, MD PhD, Principal investigator, Hospital Clínic Universitari
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03169621
- Sponsor's protocol ID
- IGX1-ECR-CS-17-01
- Acronym
- ChEndometritis
- Status last verified
- Aug 2018
- First submitted
- 19 May 2017
- Last updated
- 26 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnosis of Chronic Endometritis in Endometrial Fluid Using Molecular Techniques to Improve the Outcomes of Assisted Reproductive Treatments
- ClinicalTrials.gov ID
- NCT03169621
- Acronym / sponsor ID
- ChEndometritis / IGX1-ECR-CS-17-01
- Conditions
- Chronic Endometritis
- Keywords
- Chronic Endometritis, Endometrial pathogens, Microbiological diagnosis, Next Generation Sequencing, Metagenomics, Endometrial receptivity
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Low patient enrolment during the recruiting period
- Enrolment
- 5 participants (actual)
- Lead sponsor
- IgenomixIndustry (pharma, biotech, devices)
- Collaborators
- Instituto de Investigacion Sanitaria INCLIVA, University of Valencia
- Study start
- 27 Apr 2017 (actual)
- Primary completion
- 26 Jun 2018 (actual)
- Study completion
- 13 Feb 2019 (actual)
- First posted
- 30 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
On day 5 of the Hormonal Replacement Therapy (after 5 days of progesterone administration), coinciding with the day of hysteroscopy indicated by the physician according to the routine clinical practice, samples of endometrial fluid (EF) and endometrial biopsy (EB) of patients with RIF will be obtained. These samples will be used for the diagnosis of CE by both classic and molecular methods. Specifically, EF sample will be analyzed by molecular techniques using Next Generation Sequencing (NGS) for the detection of infectious agents. 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), another part will be subjected to microbiological analysis and the third part will be analyzed using histological techniques. In this way, comparisons will be made between the different diagnostic methods of CE in the two sample types (EF and EB) and the efficacy values of the new diagnostic test (sensitivity, specificity, positive and negative predictive values and Receiving Operating Characteristic curves) will be obtained using the microbiological diagnosis as a reference (gold standard method).
Patients with a negative outcome for CE (approximately 40%) will continue with the expected assisted reproduction treatment (ART) according to the clinic's standard protocol and patients with a positive outcome for CE (approx. 60%) will receive antibiotic treatment according to usual clinical practice (time and type of antibiotic will be different according to the microbiological diagnosis). Once this treatment is completed, the improvement of these patients will be confirmed obtaining a second sample of EF and EB. The Assisted Reproductive Treatment (ART) will be performed once the specialist considers it appropriated.
Finally, reproductive rates will be correlated with the diagnosis of CE. Therefore, an observational analytical study, in which a comparison of the ART results before and after its diagnosis of CE, will be carried out. The reproductive impact of an altered endometrial microbiota will be assessed analyzing the implantation rates, pregnancy and ongoing pregnancy.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with RIF | – | Procedure: Endometrial Biopsy and endometrial fluid collectionPatients 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). |
Who may qualify
- Ages
- 18 to 38 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- 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) .
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Endometrial Biopsy and endometrial fluid collectionOn 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. | Procedure or surgery | Patients with RIF |
Primary outcome
Developing of a new non invasive diagnosis test by Next Generation Sequencing (NGS) analysis for patients diagnosed with chronic endometritis (CE).
Time frame: 24 months
DNA analysis by NGS using endometrial fluid for the CE diagnose.
6 secondary outcomes
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).
Time frame: 24 months
Qualitative study of the endometrial microbiome by classical and molecular methods in order to determine their influence in the CE diagnose.
Time frame: 24 months
Quantitative study of the endometrial microbiome by classical and molecular methods in order to determine their influence in the CE diagnose.
Time frame: 24 months
Relationship between the implantation rate and the diagnosis of CE, by molecular and classical methods, in patients undergoing assisted reproduction treatments (ART).
Time frame: 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).
Time frame: 5 months
Relationship between the live birth rate and the diagnosis of CE, by molecular and classical methods, in patients undergoing assisted reproduction treatments (ART).
Time frame: 9 months
Results and safety
The study was stopped early (reason given: Low patient enrolment during the recruiting period). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carlos Simón, MD PhD study chair
Igenomix
Gemma Arribas, MD PhD principal investigator
Hospital Clínic Universitari
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Endometritis, run by Igenomix at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Low patient enrolment during the recruiting period). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Developing of a new non invasive diagnosis test by Next Generation Sequencing (NGS) analysis for patients diagnosed with chronic endometritis (CE). (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2019.