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2021 Fiscal Year Research-status Report

Analysis of embryo receptivity mechanism via regulation of cell senescence in decidualizing human endometrial stromal cells

Research Project

Project/Area Number 18K09273
Research InstitutionJuntendo University

Principal Investigator

黒田 恵司  順天堂大学, 医学部, 非常勤講師 (60459162)

Project Period (FY) 2018-04-01 – 2023-03-31
Keywords不育症 / 不妊症 / 子宮内膜 / 血栓性素因 / 甲状腺 / 流産
Outline of Annual Research Achievements

これまで行ってきた子宮内膜の研究より確立した、体外受精を繰り返しても妊娠しない着床不全症例に対する、甲状腺機能、血栓性素因、免疫機構、子宮内環境の精査・加療OPTIMUM (OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu) treatment strategy (以下OPTIMUM)を、流産を繰り返す不育症の患者に行い論文化した。
2回以上連続して流産した既往のある女性に対し、以下の検査を行った:子宮鏡検査、子宮内膜組織のCD138免疫染色および子宮内細菌培養検査、血清Th1・Th2細胞値、ビタミンD値、甲状腺検査、血栓性素因検査。治療として子宮内病変に子宮鏡手術、慢性子宮内膜炎に抗菌薬治療、Th1/Th2細胞比の異常高値にビタミンD補充およびタクロリムスの投与、甲状腺機能異常に対し甲状腺専門医の精査および低下症にレボチロキシン投与、血栓性素因に対し低用量アスピリンを投与した。OPTIMUM後の妊娠成績を確認した。
対象患者の不育症のリスク因子は、子宮内病変66例(57.4%)、Th1/Th2細胞比高値50例(43.5%)、甲状腺機能異常33例(28.7%)、血栓性素因33例(28.7%)であった。OPTIMUM群とコントロール群のそれぞれの初回妊娠後の生産率は、40歳未満で78.1%、42.3% (p=0.002)、40歳以上で55.6%、30.0% (p=0.09)で、40歳未満でOPTIMUM群が有意に高かった。
OPTIMUMは、世界で初めて着床不全と不育症を同時に治療が可能な方法である。40歳以上では年齢に伴う流産率が高く、有意差を認めなかったが、着床前スクリーニングなどを併用することで妊娠成績の向上が期待できる。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

予定していた研究は順調でさらに基礎研究を活かした臨床研究に進んでいる。

Strategy for Future Research Activity

現在、子宮内環境の異常である慢性子宮内膜炎のリスク因子となる子宮疾患についてデータを解析し、論文化を進め、積極的に成果を発信していく予定である。

Causes of Carryover

コロナ禍となり、予定していた学会発表が無くなったり、ウェブのみとなったため、次年度の使用額が生じた。また今後は、さらなる論文の校正や投稿、学会発表のために使用する予定である。

  • Research Products

    (14 results)

All 2022 2021

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 5 results,  Invited: 5 results)

  • [Journal Article] Optimal individualization of patient‐oriented ovarian stimulation in Japanese assisted reproductive technology clinics, a review for unique setting with advanced‐age patients2022

    • Author(s)
      Kuroda Keiji、Katagiri Yukiko、Ishihara Osamu
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 48 Pages: 521~532

    • DOI

      10.1111/jog.15150

    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of the risk factors and treatment for repeated implantation failure: OPtimization of Thyroid function, IMmunity, and Uterine Milieu (OPTIMUM) treatment strategy2021

    • Author(s)
      Kuroda Keiji、Matsumura Yuko、Ikemoto Yuko、Segawa Tomoya、Hashimoto Tomoko、Fukuda Junichiro、Nakagawa Koji、Uchida Toyoyoshi、Ochiai Asako、Horimoto Yoshiya、Arakawa Atsushi、Nojiri Shuko、Itakura Atsuo、Sugiyama Rikikazu
    • Journal Title

      American Journal of Reproductive Immunology

      Volume: 85 Pages: e13376

    • DOI

      10.1111/aji.13376

    • Peer Reviewed
  • [Journal Article] Novel approaches to the management of recurrent pregnancy loss: The OPTIMUM (OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu) treatment strategy2021

    • Author(s)
      Kuroda Keiji、Ikemoto Yuko、Horikawa Takashi、Moriyama Azusa、Ojiro Yuko、Takamizawa Satoru、Uchida Toyoyoshi、Nojiri Shuko、Nakagawa Koji、Sugiyama Rikikazu
    • Journal Title

      Reproductive Medicine and Biology

      Volume: 20 Pages: 524~536

    • DOI

      10.1002/rmb2.12412

    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of the therapeutic effects of hysteroscopic polypectomy with and without doxycycline treatment on chronic endometritis with endometrial polyps2021

    • Author(s)
      Kuroda Keiji、Takamizawa Satoru、Motoyama Hiroshi、Tsutsumi Ryo、Sugiyama Rie、Nakagawa Koji、Sugiyama Rikikazu、Kuribayashi Yasushi
    • Journal Title

      American Journal of Reproductive Immunology

      Volume: 85 Pages: e13392

    • DOI

      10.1111/aji.13392

    • Peer Reviewed
  • [Journal Article] Increasing number of implantation failures and pregnancy losses associated with elevated Th1/Th2 cell ratio2021

    • Author(s)
      Kuroda Keiji、Nakagawa Koji、Horikawa Takashi、Moriyama Azusa、Ojiro Yuko、Takamizawa Satoru、Ochiai Asako、Matsumura Yuko、Ikemoto Yuko、Yamaguchi Koushi、Sugiyama Rikikazu
    • Journal Title

      American Journal of Reproductive Immunology

      Volume: 86 Pages: e13429

    • DOI

      10.1111/aji.13429

    • Peer Reviewed
  • [Journal Article] Therapeutic effects of an oral gonadotropin‐releasing hormone receptor antagonist, relugolix, on preventing premature ovulation in mild ovarian stimulation for IVF2021

    • Author(s)
      Nakao Kazuki、Kuroda Keiji、Horikawa Takashi、Moriyama Azusa、Juen Hiroyasu、Itakura Akiko、Watanabe Hideaki、Takamizawa Satoru、Ojiro Yuko、Nakagawa Koji、Sugiyama Rikikazu
    • Journal Title

      Reproductive Medicine and Biology

      Volume: 21 Pages: e12422

    • DOI

      10.1002/rmb2.12422

    • Peer Reviewed / Open Access
  • [Presentation] Analysis of the therapeutic effects of hysteroscopic polypectomy on CHRONIC ENDOMETRITIS with endometrial polyps2021

    • Author(s)
      Keiji Kuroda, Satoru Takamizawa, Hiroshi Motoyama, Ryo Tsutsumi, Rie Sugiyama, Koji Nakagawa, Rikikazu Sugiyama, Yasushi Kuribayashi
    • Organizer
      21st APAGE Annual Congress (APAGE 2021)
    • Int'l Joint Research
  • [Presentation] Repeated Implantation Failure: Do We Have A Test Yet?2021

    • Author(s)
      Keiji Kuroda
    • Organizer
      The 10th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE)
    • Int'l Joint Research / Invited
  • [Presentation] Analysis of risk factors for chronic endometritis in infertile women who underwent hysteroscopic surgery for intrauterine disease2021

    • Author(s)
      Keiji Kuroda, Satoru Takamizawa, Takashi Horikawa, Yuko Ojiro, Azusa Moriyama, Hiroyasu Juen, Kazuki Nakao, Koji Nakagawa, Yasushi Kuribayashi, Rikikazu Sugiyama
    • Organizer
      The 10th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE)
    • Int'l Joint Research
  • [Presentation] Efficacy of Periconceptional Multivitamin Supplementation on Folate and Homocysteine Concentrations Depending on Genetic Variants of MTHFR in Infertile Women2021

    • Author(s)
      Keiji Kuroda 1,2, Takashi Horikawa 1, Yoko Gekka 1, Azusa Moriyama 1, Kazuki Nakao 1, Hiroyasu Juen 1, Satoru Takamizawa 1, Yuko Ojiro 1, Koji Nakagawa 1 and Rikikazu Sugiyama
    • Organizer
      FIGO 2021 World congress of gynecology and obstetrics
    • Int'l Joint Research
  • [Presentation] Mild ovarian stimulation2021

    • Author(s)
      Keiji Kuroda
    • Organizer
      Fertility acadeMe webinar Controlled ovarian stimulation: lessons learned from Japan
    • Int'l Joint Research / Invited
  • [Presentation] 子宮内膜脱落膜化の異常と着床不全2021

    • Author(s)
      黒田恵司
    • Organizer
      第39回日本受精着床学会総会・学術講演会
    • Invited
  • [Presentation] 高齢不妊治療に対する治療戦略 子宮に関する知見から2021

    • Author(s)
      黒田恵司
    • Organizer
      第73回日本産科婦人科学会学術講演会
    • Invited
  • [Presentation] 慢性子宮内膜炎を再検討する2021

    • Author(s)
      黒田恵司
    • Organizer
      第36回日本生殖免疫学会総会・学術集会
    • Invited

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Published: 2022-12-28  

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