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Relationship between intrauterine infection and endometriosis and its association with infertility

Research Project

Project/Area Number 18K09268
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Khan Khaleque  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60336162)

Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsendometriosis / uterine infection / metagenome assay / tissue inflammation / chronic endometritis / LVFX / GnRHa / LVFX/GnRHa / inflammation / metagenone / エンドメトリオーシス / メタゲノム / 子宮内膜症 / 腟内細菌叢
Outline of Final Research Achievements

We investigated the intrauterine microbial colonization in endometrial samples . Endometrial and endometriotic samples were collected from 53 women with endometriosis and 47 control women and were treated with levofloxacin (LVFX, or GnRHa before surgery.16S rDNA metagenome assay indicated that treatment with either of LVFX or GnRHa+LVFX significantly decreased some components of major bacterial genera comparing to untreated group.These findings corresponded with decreases tissue inflammation. Immunohistochemical analysis with antibody against CD138 indicated that the occurrence rate of chronic endometritis was significantly decreased after GnRHa+LVFX treatment comparing to GnRHa treatment group (P=0.041).
These findings suggest the effectiveness of a broad-spectrum antibiotic, as a non-hormonal agent, in improving uterine infection in human endometriosis. Future study is needed to confirm the validity of antibiotic treatment in improving fertility outcome in women with endometriosis.

Academic Significance and Societal Importance of the Research Achievements

通常のホルモン治療では様々な副作用があります。私共の研究では内膜症の発生に関する新しいメカニズムを報告しました。また非ホルモン治療として抗生物質が内膜症の治療に有効であり、不妊症の改善に役立つ可能性があります。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (53 results)

All 2024 2023 2022 2021 2020 2019 2018

All Journal Article (20 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 20 results,  Open Access: 9 results) Presentation (27 results) (of which Int'l Joint Research: 17 results,  Invited: 27 results) Book (6 results)

  • [Journal Article] Bacterial infection in endometriosis: A silver-lining for the development of new non-hormonal therapy?2024

    • Author(s)
      Khan KN, de Ziegler D, Guo SW.
    • Journal Title

      Hum Reprod

      Volume: 39(4) Pages: 623-631

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The role of innate and adaptive immunity in endometriosis2024

    • Author(s)
      Khan KN, Guo SW, Ogawa K, Fujishita A, Mori T.
    • Journal Title

      J Reprod. Immunol.

      Volume: 163 Pages: 104-116

    • DOI

      10.1016/j.jri.2024.104242

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Neonatal Uterine bleeding: risk factors and it’s association with endometriosis-related symptoms later in life2024

    • Author(s)
      Ogawa K, Khan KN, Fujishita A, Itoh K, Teramukai S, KItawaki J, Mori T.
    • Journal Title

      Eur J Obstet. Gynecol. Reprod. Biol

      Volume: 293 Pages: 146-155

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Is neonatal uterine bleeding responsible for early-onset endometriosis?2023

    • Author(s)
      Ogawa Kanae、Khan Khaleque N、Kuroboshi Haruo、Koshiba Akemi、Shimura Koki、Tajiri Tatsuro、Fumino Shigehisa、Fujita Hiroyuki、Okubo Tomoharu、Fujiwara Yoichiro、Horiguchi Go、Teramukai Satoshi、Fujishita Akira、Itoh Kyoko、Guo Sun-Wei、Kitawaki Jo、Mori Taisuke
    • Journal Title

      Reproductive Biology and Endocrinology

      Volume: 21 Issue: 1 Pages: 56-65

    • DOI

      10.1186/s12958-023-01099-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association between tissue stress reaction and ACE2/TMPRSS2 expression in endometria of reproductive aged women before and during Covid-19 pandemic2023

    • Author(s)
      Ogawa K, Khan KN, Fujishita A, Kitawaki J, Mori T.
    • Journal Title

      BMC Women’s Health

      Volume: 23 Issue: 1 Pages: 229-238

    • DOI

      10.1186/s12905-023-02378-0

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A targeted educational program improves the fundamental knowledge on menstrual pain and endometriosis in young women: The Endometriosis Awareness Promotion Project2022

    • Author(s)
      Khan KN, Ogawa K, Iwasa K, Kuroboshi H, Okimura H, Koshiba A et al.
    • Journal Title

      Reprod Biomed Online

      Volume: 45(6) Issue: 6 Pages: 1216-1229

    • DOI

      10.1016/j.rbmo.2022.07.009

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pathogenesis of human adenomyosis: current understanding and its association with infertility2022

    • Author(s)
      Khan KN, Fujishita A, Mori T
    • Journal Title

      J Clin Med.

      Volume: 11 Issue: 14 Pages: 4057-4086

    • DOI

      10.3390/jcm11144057

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Occurrence of chronic endometritis in different types of human adenomyosis2022

    • Author(s)
      Khan KN, Fujishita A, Ogawa K, Koshiba A, Mori T, Itoh K, Nakashima M, Kitawaki J
    • Journal Title

      Reprod Med Biol.

      Volume: 21 Issue: 1

    • DOI

      10.1002/rmb2.12421

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Occurrence of chronic endometritis in different types of human adenomyosis.2022

    • Author(s)
      Khan KN, Fujishita A, Ogawa K, Koshiba A, Mori T, Itoh K, Nakashima M, Kitawaki J.
    • Journal Title

      Reprod Med Biol.

      Volume: 21 Pages: 2421-2426

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Decreased occurrence of endometriosis in women with Chlamydia trachomatis infection2021

    • Author(s)
      Khan Khaleque N.、Fujishita Akira、Kitajima Michio、Ishimaru Tadayuki、Ogawa Kanae、Koshiba Akemi、Mori Taisuke、Kitawaki Jo
    • Journal Title

      American Journal of Reproductive Immunology

      Volume: 86 Issue: 6 Pages: 13498-13503

    • DOI

      10.1111/aji.13498

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Levofloxacin or GnRHa treatment decreases intrauterine microbial colonization in human endometriosis2021

    • Author(s)
      Khan KN, Fujishita A, Muto H, Masumoto H, Ogawa K, Koshiba A, Mori T, Itoh K, Teramukai S, Matsuda K, Nakashima M, Kitawaki J.
    • Journal Title

      Eur J Obstet Gynecol Reprod Biol.

      Volume: 264 Pages: 103-116

    • DOI

      10.1016/j.ejogrb.2021.07.014

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] An axonemal alteration in apical endometria of human adenomyosis2021

    • Author(s)
      Khan KN, Fujishita A, Suematsu T, Ogawa K, Koshiba A, Mori T, Itoh K, Teramukai S, Matsuda K, Nakashima M, Kitawaki J
    • Journal Title

      Hum Reprod

      Volume: 36(6) Issue: 6 Pages: 1574-1589

    • DOI

      10.1093/humrep/deab090

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression profiles of E/P receptors and fibrosis in GnRHa-treated and -untreated women with different uterine leiomyomas2021

    • Author(s)
      Khan KN, Fujishita A, Koshiba A, Ogawa K, Mori T, Ogi H, Itoh K, Kitawaki J
    • Journal Title

      PLoS ONE

      Volume: 15(11) Issue: 11 Pages: e0242246-e0242246

    • DOI

      10.1371/journal.pone.0242246

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Letter to Editor: Evidence in support for the progressive nature of ovarian endometriomas2020

    • Author(s)
      Khan KN, Fujishita A, Koshiba A, Kitawaki J
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 105(11) Issue: 11 Pages: 1-2

    • DOI

      10.1210/clinem/dgaa541

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential levels of regulatory T-cells and T-helper-17 cells in women with early and advanced endometriosis2019

    • Author(s)
      Khan KN, Yamamoto K, Fujishita A, Muto H, Koshiba A, Kuroboshi H, Saito S, Teramukai S, Nakashima M, Kitawaki J.
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: May 1 Issue: 10 Pages: 4715-4729

    • DOI

      10.1210/jc.2019-00350

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biological differences between intrinsic and extrinsic adenomyosis with coexisting deep infiltrating endometriosis2019

    • Author(s)
      Khan KN, Fujishita A, Koshiba A, Kuroboshi H, Mori T, Ogi H, Itoh K, Nakashima M, Kitawaki J
    • Journal Title

      Reprod Biomed Online

      Volume: 38(6) Issue: 2 Pages: 343-353

    • DOI

      10.1016/j.rbmo.2019.03.210

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Association between FOXP3+ regulatory T-cells and occurrence of peritoneal lesions in women with ovarian endometrioma and dermoid cysts2019

    • Author(s)
      Khan KN, Yamamoto K, Fujishita A, Koshiba A, Kuroboshi H, Sakabayashi S, Teramukai S, Nakashima M, Kitawaki J.
    • Journal Title

      Reprod Biomed Online

      Volume: Jan 31 Issue: 6 Pages: 857-869

    • DOI

      10.1016/j.rbmo.2019.01.011

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biological differences between focal and diffuse adenomyosis and response to hormonal treatment2019

    • Author(s)
      Khan KN, Fujishita A, Koshiba A, Mori T, Kuroboshi H, Ogi H, Itoh K, Nakashima M, Kitawaki J
    • Journal Title

      Reprod Biomed Online

      Volume: 38(4) Issue: 4 Pages: 634-646

    • DOI

      10.1016/j.rbmo.2018.12.015

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Bacterial contamination hypothesis: a new concept in endometriosis (review).2018

    • Author(s)
      Khan KN, Fujishita A, Hiraki K, Kitajima M, Nakashima M, Fushiki S, Kitawaki J.
    • Journal Title

      Reprod Med Biol.

      Volume: 17(2) Issue: 2 Pages: 125-133

    • DOI

      10.1002/rmb2.12083

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association between ovarian endometrioma and ovarian reserve (review).2018

    • Author(s)
      Kitajima M, Khan KN, Harada A, Taniguchi K, Inoue T, Kaneuchi M, Miura K, Masuzaki H.
    • Journal Title

      Front Biosci (Elite Ed).

      Volume: 10 Pages: 92-102

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] A targeted educational program to improve awareness and fundamental knowledge on menstrual pain and endometriosis among young women in Asia2024

    • Author(s)
      Khan KN
    • Organizer
      The 37th Annual Meeting of Thailand Society of Obstetrics and Gynecology
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Occult microscopic endometriosis: an undetectable finding in visually normal peritoneum by laparoscopy2024

    • Author(s)
      Khan KN
    • Organizer
      The 2nd International Scientific conference on Endometriosis
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Patterns of menstrual cycle, menstrual pain and medication usage among young women of high-income and middle-income countries2024

    • Author(s)
      Khan KN
    • Organizer
      The 13th Annual Meeting of the Taiwan Society of Endometriosis
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Pathogenesis of human adenomyosis: an update and its association with infertility2024

    • Author(s)
      Khan KN
    • Organizer
      The 12th Asian Congress on Endometriosis
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Bacterial contamination hypothesis: a new concept in endometriosis2023

    • Author(s)
      Khan KN, Ogawa K, Fujishita A, Kitawaki J, Mori T.
    • Organizer
      The 11th Asian Congress on Endometriosis
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Pathogensis of human adenomyosis: current understanding and its association with infertility (educational lecture)2023

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J, Mori T
    • Organizer
      The 44th Japan Endometriosis Congress
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Role of innate and adaptive immunity in endometriosis (educational lecture)2022

    • Author(s)
      Khan KN, Fujishita A, Mori T
    • Organizer
      The 37th Annual Meeting of the Japan Society of Reproductive Immunology
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] An axonemal alteration in apical endometria of human adenomyosis: an implication in infertility2022

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J, Mori T
    • Organizer
      The 12th Conference on Hormone-Dependent Gynecologic Diseases
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Bacterial contamination hypothesis: a new concept in endometriosis2021

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J, Mori T
    • Organizer
      The 9th Asian Congress on Endometriosis (9th ACE)
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Current status, development and problems of adolescent endometriosis2021

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J, Mori T
    • Organizer
      The Annual Scientific Congress of Vietnam Association of Gynecology & Obstetrics
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Adolescent endometriosis: its development and problems in Asia2021

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J, Mori T
    • Organizer
      The 1st International Conference of Endometriosis Adenomyosis Society of Bangladesh (EASB)
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Levofloxacin and GnRHa treatment decreases intrauterine microbial colonization in women with endometriosis.2021

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J, Mori T
    • Organizer
      The 14th World Congress on Endometriosis
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Biological differences between intrinsic and extrinsic adenomyosis with coexisting deep infiltrating endometriosis2021

    • Author(s)
      Khan KN
    • Organizer
      The 14th World Congress on Endometriosis (14th WCE)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Levofloxacin or GnRHa decreases uterine infection, tissue inflammation, cell proliferaiton and angiogenesis in human endometriosis2021

    • Author(s)
      Khan KN
    • Organizer
      The 14th World Congress on Endometriosis (14th WCE)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Biological differences between intrinsic and extrinsic adenomyosis with coexisting deep infiltrating endometriosis2020

    • Author(s)
      Khan KN
    • Organizer
      ASEA Masterclass Seminar
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of EMT in adenomyosis and its association with infertility2020

    • Author(s)
      Khan KN
    • Organizer
      Singapore National OBGY Congress
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Bacterial contamination hypothesis: a new concept in endometriosis2020

    • Author(s)
      Khan KN
    • Organizer
      FOGSI International Endometriosis Conference (IEC)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Adolescent endometriosis: current status and problems in endometriosis2019

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J
    • Organizer
      The 32nd Vietnam National Congress of Obstetrics and Gynecology
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Differential occurrence of peritoneal lesions in women with ovarian endometrioma and non-endometrioma2019

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J
    • Organizer
      Taiwan Endometiosis Society2019 International Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of epithelial-mesenchymal transition in human adenomyosis2019

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J
    • Organizer
      Taiwan Endometiosis Society2019 International Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Bacterial contamination hypothesis: a new concept in endometriosis2019

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J
    • Organizer
      The 8th Asian Conference on Endometriosis (8th ACE)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Adolescent endometriosis: etiology and development2019

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J
    • Organizer
      The 26th Asia and Oceania Federation of Obstetrics and Gynecology (AOFOG)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Pathogenesis of adenomyosis and its association with infertility2019

    • Author(s)
      Khan KN, Fujishita A, Koshiba A, Mori T, Okimura H, Kitawaki J.
    • Organizer
      The 40th Japan Endometriosis Congress
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Role of epithelial-mesenchymal transition in human adenomyosis2018

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J.
    • Organizer
      The 4th Annual Congress of the Society of Endometriosis and Uterine Disorders (SEUD)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Bacterial contamination in endometriosis: a re-confirmation by molecular method2018

    • Author(s)
      Khan KN, Fujishita A, Koshiba A, Mori T, Okimura H, Kitawaki J.
    • Organizer
      The 7th Asian Congress of Endometriosis
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Occult microscopic endometriosis2018

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J.
    • Organizer
      European Society of Gynecologic Endoscopy Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Adolescent endometriosis: current status and its problems in Asia2018

    • Author(s)
      Khan KN, Fujishita A, Kitawaki J.
    • Organizer
      Endometriosis Seminar at the University of Philippines
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] Endometriosis and adenomyosis2022

    • Author(s)
      Khan KN
    • Total Pages
      236
    • Publisher
      Springer Nature
    • Related Report
      2022 Research-status Report
  • [Book] Immunology of endometriosis2021

    • Author(s)
      Khan KN, Fujishita A, Tanaka Y, Kitawaki J
    • Publisher
      Elsevier Inc.
    • Related Report
      2021 Research-status Report
  • [Book] Immunology of Endometriosis2020

    • Author(s)
      Khan KN, Fujishita A, Tanaka Y, Kitawaki J
    • Publisher
      Elsevier Inc
    • Related Report
      2020 Research-status Report
  • [Book] Endometriosis and Adenomyosis2020

    • Author(s)
      Khan KN, Ogawa K
    • Publisher
      Nakayama Shoten
    • Related Report
      2020 Research-status Report
  • [Book] Obstetrics and Gynecology2019

    • Author(s)
      Khan KN, Kuroboshi H, Fujishita A
    • Publisher
      Diagnosis and Treatment Company
    • Related Report
      2019 Research-status Report
  • [Book] Uterine fibroids and adenomyosis2018

    • Author(s)
      Khan KN
    • Publisher
      The Springer publishing Co.
    • ISBN
      9789811071669
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2025-01-30  

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