Diagnostics of Chronic Endometritis in Infertility
Condition: Infertility Unexplained
MeSH terms: Infertility; Endometritis
Study type: Interventional

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:

        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 mm2

        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 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.
    

Intervention name(s): Ofloxacin + Metronidazole
Intervention type(s): Drug
Intervention description(s): Ofloxacin 2x200mg orally for 10 days + Metronidazole 1x500 mg vaginally for 10 days
Intervention MeSH terms: Metronidazole; Ofloxacin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective randomized open-label comparative parallel-group study
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Infertility Unexplained; Chronic endometritis; Office hysteroscopy