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Diagnostics of Chronic Endometritis in Infertility

Primary Purpose

Infertility Unexplained

Status
Active
Phase
Not Applicable
Locations
Poland
Study Type
Interventional
Intervention
Ofloxacin + Metronidazole
Sponsored by
Jagiellonian University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Infertility Unexplained focused on measuring Infertility Unexplained, Chronic endometritis, Office hysteroscopy

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: age 18-45 years lack of previous diagnosis and treatment due to suspected pathology of the uterine cavity lack of active infection of the reproductive tract Exclusion Criteria: pelvic surgery performed within 6 months preceding the hysteroscopy confirmed pelvic endometriosis antibiotic or probiotic treatment within 3 months preceding the hysteroscopy

Sites / Locations

  • Jagiellonian University Medical College, Department of Gynecology and Obstetrics

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Antibiotic therapy

Control

Arm Description

Women with infertility diagnosed with CE undergoing empirical antibiotic therapy

Women with infertility diagnosed with CE not subjected to empirical antibiotic therapy

Outcomes

Primary Outcome Measures

The incidence of CE in women with idiopathic infertility
Estimation of the percentage of women diagnosed with CE in the population of women with idiopathic infertility
Determination of the cut-off point of the number of plasma cells/1 mm2 defining CE
Diagnostic compatibility assessment of immunohistochemistry and histopathology will be performed to estimate the cut-off point for the number of plasma cells defining CE using the ROC (Receiver Operating Characteristic) curve

Secondary Outcome Measures

Assessment of the reliability of polyp visualization in diagnosing CE
The percentage of women with CE and a hysteroscopy-visible endometrial polyp and without a polyp will be calculated and compared
Assessment of the reliability of the visualization of focal endometrial hyperemia in the diagnosis of CE
The percentage of women with CE and hysteroscopy-visible focal hyperemia and without hyperaemia will be calculated and compared
Assesment of the reliability of the visualization of diffuse endometrial hyperemia in the diagnosis of CE
The percentage of women with CE and hysteroscopy-visible diffuse hyperaemia and without hyperaemia will be calculated and compared
Assessment of the reliability of the visualization of endometrial micropolyps in the diagnosis of CE
The percentage of women with CE and hysteroscopy-visible micropolyps and without micropolyps will be calculated and compared
Assessment of the reliability of the visualization of endometrial edema in the diagnosis of CE
The proportion of women with CE and hysteroscopy-visible endometrial edema and without endometrial edema will be calculated and compared
Evaluation of the effectiveness of antibiotic therapy in the context of reducing the number of plasma cells/1 mm2
The number of plasma cells/1 mm2 will be calculated and compared among women who received antibiotic therapy in the course of CE and untreated women
Evaluation of the effectiveness of antibiotic therapy in the context of visual normalization of the uterine cavity in follow-up hysteroscopy
The percentage of women with persistent hysteroscopic CE symptoms: visualization of focal hyperemia or diffuse hyperemia or endometrial micropolyps or endometrial edema in follow-up hysteroscopy will be assessed and compared among women who received antibiotic therapy in the course of CE and untreated women
Evaluation of the effectiveness of antibiotic therapy in the context of normalization of histopathological results of a control endometrial biopsy
The percentage of women with persistent histopathological CE symptoms: presence of plasma cells and/or other inflammatory cells (lymphocytes or neutrophilic granulocytes or histiocytes/macrophages or eosinophilic granulocytes) destructing the endometrial tubuli among women who received antibiotic therapy in the course of CE and untreated women will be evaluated and compared in follow-up hysteroscopic endometrial biopsy
Evaluation of the effectiveness of antibiotic therapy in the treatment of CE - dependent infertility
Pregnancy rates will be assessed and compared among women who received antibiotics for CE and untreated women

Full Information

First Posted
June 29, 2023
Last Updated
July 7, 2023
Sponsor
Jagiellonian University
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1. Study Identification

Unique Protocol Identification Number
NCT05946655
Brief Title
Diagnostics of Chronic Endometritis in Infertility
Official Title
Evaluation of the Congruity of Methods Used in the Diagnostics of Chronic Endometritis in the Course of Infertility and the Effectiveness of Antibiotic Therapy in the Context of Remission of Symptoms and Obstetric Results
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 1, 2021 (Actual)
Primary Completion Date
October 30, 2022 (Actual)
Study Completion Date
September 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Jagiellonian University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Chronic endometritis (CE) is characterized by the presence of atypical plasma cell infiltrates (CD138 positive) in the endometrial stroma. Recent analyzes suggest that CE adversely affects fertility by reducing endometrial receptivity, impairing decidualization and uterine contractility, thus increasing the risk of recurrent pregnancy loss and implantation failure. It is likely that a significant proportion of idiopathic infertility cases are due to CE. The diagnosis of CE is a challenge because the clinical examination and transvaginal ultrasonography are considered non-specific. The recent scientific research has been aimed at identifying hysteroscopic CE diagnostic criteria and establishing the compatibility of ultrasonographic, hysteroscopic, histopathological (including the use of immunohistochemical testing with antibodies against human CD138) and microbiological diagnoses. Preliminary literature results suggested that successful treatment of CE with antibiotics could improve live birth rates.
Detailed Description
The main objective of the study is to estimate the incidence of chronic endometritis (CE) in the population of women of childbearing age who underwent hysteroscopy for infertility. The specific objectives are as follows: Estimation of the diagnostic congruity of hysteroscopic, histopathological and microbiological diagnoses of CE Estimation of the effectiveness of empirical antibiotic therapy in the treatment of CE, confirmed by normalization of the hysteroscopic appearance of the uterine cavity, normalization of histopathological results of endometrial biopsies and decrease in plasma cell count/1 mm2 Estimation of the percentage of clinical pregnancies achieved in women subjected to empiric antibiotic therapy for CE vs. in women without treatment. The study group will consist of women of childbearing age subjected hysteroscopy due to idiopathic infertility. The prerequisite for hysteroscopy is a normal cervical cytology result, a negative blood pregnancy test, a normal vaginal biocenosis and the first phase of the cycle. During hysteroscopy, the following will be performed: visual inspection of the uterine cavity in search of focal lesions and features of the endometrium suggestive of CE, such as: focal or diffuse hyperemia, micropolyps, stromal edema, then collection of washings from the uterine cavity for microbiological examination (aerobic and anaerobic culture, PCR for Chlamydia, culture for Mycoplasma, Ureaplsma) and excision of the focal lesion or endometrial biopsy. The extracted tissue material will be subjected to standard histopathological examination with hematoxylin and eosin staining. Additional immunohistochemical staining with Monoclonal Mouse Anti-Human CD138 antibodies will be used to detect plasmocytes. The cut-off point for the number of CE-defining plasmocytes will be determined by the Receiver Operating Characteristic (ROC) curve. Women with infertility diagnosed with CE will be randomized to 2 arms: 1) ofloxacin 2x200 mg orally for 10 days + metronidazole 1x500 mg vaginally for 10 days, 2) control arm (no treatment). After 3 cycles from surgery or completion of treatment, women will undergo a repeat hysteroscopy for a visual assessment of the uterine cavity and a follow-up endometrial biopsy. The percentage of women with improvement in the clinical appearance of the uterine cavity, normalization of histopathology and persistent CE in both arms will be determined. Data will be obtained on the results of infertility treatment (obtaining a clinical pregnancy) within 12 months of the procedure or completion of antibiotic therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility Unexplained
Keywords
Infertility Unexplained, Chronic endometritis, Office hysteroscopy

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Prospective randomized open-label comparative parallel-group study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Antibiotic therapy
Arm Type
Experimental
Arm Description
Women with infertility diagnosed with CE undergoing empirical antibiotic therapy
Arm Title
Control
Arm Type
No Intervention
Arm Description
Women with infertility diagnosed with CE not subjected to empirical antibiotic therapy
Intervention Type
Drug
Intervention Name(s)
Ofloxacin + Metronidazole
Intervention Description
Ofloxacin 2x200mg orally for 10 days + Metronidazole 1x500 mg vaginally for 10 days
Primary Outcome Measure Information:
Title
The incidence of CE in women with idiopathic infertility
Description
Estimation of the percentage of women diagnosed with CE in the population of women with idiopathic infertility
Time Frame
3 months
Title
Determination of the cut-off point of the number of plasma cells/1 mm2 defining CE
Description
Diagnostic compatibility assessment of immunohistochemistry and histopathology will be performed to estimate the cut-off point for the number of plasma cells defining CE using the ROC (Receiver Operating Characteristic) curve
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Assessment of the reliability of polyp visualization in diagnosing CE
Description
The percentage of women with CE and a hysteroscopy-visible endometrial polyp and without a polyp will be calculated and compared
Time Frame
3 months
Title
Assessment of the reliability of the visualization of focal endometrial hyperemia in the diagnosis of CE
Description
The percentage of women with CE and hysteroscopy-visible focal hyperemia and without hyperaemia will be calculated and compared
Time Frame
3 months
Title
Assesment of the reliability of the visualization of diffuse endometrial hyperemia in the diagnosis of CE
Description
The percentage of women with CE and hysteroscopy-visible diffuse hyperaemia and without hyperaemia will be calculated and compared
Time Frame
3 months
Title
Assessment of the reliability of the visualization of endometrial micropolyps in the diagnosis of CE
Description
The percentage of women with CE and hysteroscopy-visible micropolyps and without micropolyps will be calculated and compared
Time Frame
3 months
Title
Assessment of the reliability of the visualization of endometrial edema in the diagnosis of CE
Description
The proportion of women with CE and hysteroscopy-visible endometrial edema and without endometrial edema will be calculated and compared
Time Frame
3 months
Title
Evaluation of the effectiveness of antibiotic therapy in the context of reducing the number of plasma cells/1 mm2
Description
The number of plasma cells/1 mm2 will be calculated and compared among women who received antibiotic therapy in the course of CE and untreated women
Time Frame
3 months
Title
Evaluation of the effectiveness of antibiotic therapy in the context of visual normalization of the uterine cavity in follow-up hysteroscopy
Description
The percentage of women with persistent hysteroscopic CE symptoms: visualization of focal hyperemia or diffuse hyperemia or endometrial micropolyps or endometrial edema in follow-up hysteroscopy will be assessed and compared among women who received antibiotic therapy in the course of CE and untreated women
Time Frame
3 months
Title
Evaluation of the effectiveness of antibiotic therapy in the context of normalization of histopathological results of a control endometrial biopsy
Description
The percentage of women with persistent histopathological CE symptoms: presence of plasma cells and/or other inflammatory cells (lymphocytes or neutrophilic granulocytes or histiocytes/macrophages or eosinophilic granulocytes) destructing the endometrial tubuli among women who received antibiotic therapy in the course of CE and untreated women will be evaluated and compared in follow-up hysteroscopic endometrial biopsy
Time Frame
3 months
Title
Evaluation of the effectiveness of antibiotic therapy in the treatment of CE - dependent infertility
Description
Pregnancy rates will be assessed and compared among women who received antibiotics for CE and untreated women
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
Evaluation of the frequency of isolation of a specific pathogen in the course of CE
Description
The co-occurrence of a specific pathogen in CE and its type will be assessed using conventional microbiological methods
Time Frame
3 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: age 18-45 years lack of previous diagnosis and treatment due to suspected pathology of the uterine cavity lack of active infection of the reproductive tract Exclusion Criteria: pelvic surgery performed within 6 months preceding the hysteroscopy confirmed pelvic endometriosis antibiotic or probiotic treatment within 3 months preceding the hysteroscopy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Jach, Prof., PhD
Organizational Affiliation
Jagiellonian University
Official's Role
Study Chair
Facility Information:
Facility Name
Jagiellonian University Medical College, Department of Gynecology and Obstetrics
City
Krakow
State/Province
Malopolska
ZIP/Postal Code
31-501
Country
Poland

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Diagnostics of Chronic Endometritis in Infertility

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