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Diagnostics of Chronic Endometritis in Infertility

Not Applicable
Completed
Conditions
Infertility Unexplained
Abnormal Uterine Bleeding
Intrauterine Disorder
Interventions
Registration Number
NCT05946655
Lead Sponsor
Jagiellonian University
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 objectives are as follows:

1. Estimation of the diagnostic congruity of hysteroscopic, histopathological and microbiological diagnoses of CE

2. 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 high power field (HPF)

3. 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 to office hysteroscopy due to intrauterine pathologies, AUB, and 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 diagnosed with CE will be assigned to 2 arms: 1) ofloxacin 2x200 mg orally for 10 days + metronidazole 1x500 mg vaginally for 10 days, 2) control arm (no treatment). In the third cycle after the primary hysteroscopy, women will undergo a follow-up office 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 24 months of the procedure or completion of antibiotic therapy.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
102
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Antibiotic therapyOfloxacin + MetronidazoleWomen diagnosed with CE undergoing empirical antibiotic therapy
Primary Outcome Measures
NameTimeMethod
Determination of the cut-off point of the number of plasma cells/1 HPF corresponding to histological CE3 months

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
NameTimeMethod
Assessment of the reliability of polyp visualization in diagnosing CE3 months

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 CE3 months

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 CE3 months

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 CE3 months

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 CE3 months

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 mm23 months

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 hysteroscopy3 months

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 biopsy3 months

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 infertility24 months

Pregnancy rates will be assessed and compared among women who received antibiotics for CE and untreated women

Evaluation of the effectiveness of antibiotic therapy in the treatment of CE - dependent abnormal uterine bleeding24 months

The rates of persistence of abnormal uterine bleeding will be assessed and compared in women who received antibiotics for CE and in untreated women.

Trial Locations

Locations (1)

Jagiellonian University Medical College, Department of Gynecology and Obstetrics

🇵🇱

Krakow, Malopolska, Poland

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