2022 Fiscal Year Research-status Report
子宮内膜症における子宮腔内細菌叢の同定と細菌環境が不妊医療に及ぼす影響
| Project/Area Number |
18K09268
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
カーン カレク 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60336162)
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Keywords | endometriosis / uterine infection / LVFX/GnRHa / inflammation |
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| Outline of Annual Research Achievements |
We examined the hypothesis that antibiotic treatment with and without gonadotropin releasing hormone agonist (GnRHa) may decrease intrauterine infection with consequent decrease in tissue inflammation, cell proliferation, angiogenesis and occurrence of chronic endometritis in women with endometriosis. We performed a prospective non-randomized observational study with collection of endometrial and endometriotic samples from 53 women with endometriosis and 47 women without endometriosis during surgery. These two groups of patients were treated with levofloxacin (LVFX, 500mg once per os) or GnRHa (1.88 mg/IM for 3 months) before surgery. Endometrial samples were analyzed by broad-range PCR amplification of bacteria targeting V5-V6 region of 16S rRNA gene. Immunohistochemistry was performed using respective target antibodies. 16S rDNA metagenome assay indicated that treatment with either LVFX or GnRHa+LVFX significantly decreased some components of major bacterial genera comparing to untreated group. Occurrence of chronic endometritis was significantly decreased after GnRHa+LVFX treatment. A significantly decreased CD68-stained macrophage infiltration, Ki-67-stained cell proliferation and CD31-stained micro-vessel density was found in endometria and endometriotic lesions with histology-proven improvement in the morphological appearance of endometriosis. These findings suggest that clinical application of a broad-spectrum antibiotic with or without GnRHa may be effective in improving uterine infection in human endometriosis.
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| Current Status of Research Progress |
Current Status of Research Progress
4: Progress in research has been delayed.
Reason
Our proposed study is already completed and published recently (Khan et al. EJOGRB 264:103-116,2021). The second part of this study is still ongoing. Due to the effect of current Covid-19 pandemic and restrictions of artificial reproductive technology (ART) procedure, we could not enroll patients and collect samples as was mentioned in the research protocol. We plan to continue our research to investigate the relationship between uterine infection and reproductive outcome.
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| Strategy for Future Research Activity |
(1) We plan to perform multinational and multi-center study on the single and combined effect of antibiotic and GnRHa to confirm the strength and validity of our completed and published study. (2) We plan to investigate molecular detection of intrauterine infection, occurrence of chronic endometritis and their effect on reproductive outcome in women undergoing ART.
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| Causes of Carryover |
(1) Due to the current Covid-19 pandemic, we could not collect endometrial samples from infertile women
undergoing artificial reproductive technology (ART). In addition, we also could not collect additional endometrial samples for the detection of chronic endometriosis in women with and without endometriosis. (2) We plan to use incurring amount in FY2023 for buying research materials or to attend a medical congress in Japan.
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