Clinical trial NCT05946655: 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
Overall status: COMPLETED
Phase: NA
Conditions: Infertility Unexplained
Abnormal Uterine Bleeding
Intrauterine Disorder
Keywords: Infertility Unexplained
Chronic endometritis
Office hysteroscopy
Abnormal Uterine Bleeding
Lead sponsor: Jagiellonian University
Sponsor class: OTHER
First posted: 2023-07-14
Enrollment: 102
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective cohort study
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Determination of the cut-off point of the number of plasma cells/1 HPF corresponding to histological CE
timeFrame: 3 months
Secondary outcomes:
measure: Assessment of the reliability of polyp visualization in diagnosing CE
timeFrame: 3 months
measure: Assessment of the reliability of the visualization of focal endometrial hyperemia in the diagnosis of CE
timeFrame: 3 months
measure: Assesment of the reliability of the visualization of diffuse endometrial hyperemia in the diagnosis of CE
timeFrame: 3 months
measure: Assessment of the reliability of the visualization of endometrial micropolyps in the diagnosis of CE
timeFrame: 3 months
measure: Assessment of the reliability of the visualization of endometrial edema in the diagnosis of CE
timeFrame: 3 months
measure: Evaluation of the effectiveness of antibiotic therapy in the context of reducing the number of plasma cells/1 mm2
timeFrame: 3 months
measure: Evaluation of the effectiveness of antibiotic therapy in the context of visual normalization of the uterine cavity in follow-up hysteroscopy
timeFrame: 3 months
measure: Evaluation of the effectiveness of antibiotic therapy in the context of normalization of histopathological results of a control endometrial biopsy
timeFrame: 3 months
measure: Evaluation of the effectiveness of antibiotic therapy in the treatment of CE - dependent infertility
timeFrame: 24 months
measure: Evaluation of the effectiveness of antibiotic therapy in the treatment of CE - dependent abnormal uterine bleeding
timeFrame: 24 months
Other outcomes:
measure: Evaluation of the frequency of isolation of a specific pathogen in the course of CE
timeFrame: 3 months
Locations:
city: Krakow
country: Poland
facility: Jagiellonian University Medical College, Department of Gynecology and Obstetrics
state: Malopolska
Study officials:
affiliation: Jagiellonian University
name: Robert Jach, Prof., PhD
role: STUDY_CHAIR
References: