Chronic endometritis
Dubrovina S.O., Bozhinskaya D.M., Gimbut V.S., Bogunova D.Yu., Tsirkunova N.S., Tsirkunova K.G.
Chronic endometritis is a chronic infectious inflammatory disease that leads to morphofunctional disorders of the endometrium. Chronic endometritis unlike acute one is almost asymptomatic and is rarely accompanied by specific clinical manifestations like pelvic pain, abnormal uterine bleeding, dyspareunia and leukorrhea. The incidence of chronic endometritis in infertile women ranges from 0.2 to 46%. Percent difference in the data is due to the lack of clear diagnostic criteria to verify the diagnosis. Morphologic examination is the diagnostic gold standard. Such pathomorphological signs as superficial edema, increased stromal density, unsynchronized differentiation between endometrial epithelium and stroma, and infiltration of the endometrium by stromal plasmacytes are the most informative. The simultaneous use of CD138 and MUM1 immunohistochemistry could potentially compensate for the weaknesses of the method in the histopathologic diagnosis of chronic endometritis. Overdiagnosis leads to unnecessary prescription of antibiotics. Antibiotic resistance has increased by 8.27 times in the last 5 years; therefore, it is necessary to search for additional alternative therapies. The study of efficacy of bovhyaluronidase azoximer in the therapy of patients who experienced chronic endometritis and had implantation failures showed that remodeling of connective tissue by bovhyaluronidase azoximer promotes improvement of reparative processes, normalization of blood circulation and receptor apparatus in the uterine cavity.
Conclusion: The absence of clear diagnostic criteria for verifying the diagnosis leads to overdiagnosis of chronic endometritis and unjustified prescription of antibacterial agents. Identifying the connection between the microbiome, chronic inflammation and the immune status of the body in the future can solve the problem of many reproductive failures, and miscarriage in particular.
Authors’ contributions: Dubrovina S.O. – developing the idea of the article, writing the article; Bozhinskaya D.M., Gimbut V.S., Bogunova D.Yu., Tsirkunova N.S., Tsirkunova K.G. – collecting the information, writing the article.
Conflicts of interest: The authors declare no possible conflicts of interest.
Funding: The study was conducted without sponsorship.
For citation: Dubrovina S.O., Bozhinskaya D.M., Gimbut V.S., Bogunova D.Yu.,
Tsirkunova N.S., Tsirkunova K.G. Chronic endometritis.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (6): 147-152 (in Russian)
https://dx.doi.org/10.18565/aig.2024.137
Keywords
References
- Mihara M., Yasuo T., Kitaya K. Precision medicine for chronic endometritis: computer aided diagnosis using deep learning model. Diagnostics (Basel). 2023; 13(5): 936. https://dx.doi.org/10.3390/diagnostics13050936.
- Song D., Feng X., Zhang Q., Xia E., Xiao Y., Xie W. et al. Prevalence and confounders of chronic endometritis in premenopausal women with abnormal bleeding or reproductive failure. Reprod. Biomed. Online 2018; 36(1): 78-83. https://dx.doi.org/10.1016/j.rbmo.2017.09.008.
- Vitagliano A., Saccardi C., Noventa M., Di Spiezio Sardo A., Saccone G., Cicinelli E. et al. Effects of chronic endometritis therapy on in vitro fertilization outcome in women with repeated implantation failure: a systematic review and meta-analysis. Fertil. Steril. 2018; 110(1): 103-112.e1. https://dx.doi.org/10.1016/j.fertnstert.2018.03.017.
- Santoro A., Travaglino A., Inzani F., Angelico G., Raffone A., Maruotti G.M. et al. The role of plasma cells as a marker of chronic endometritis: a systematic review and meta-analysis. Biomedicines. 2023; 11(6): 1714. https://dx.doi.org/10.3390/biomedicines11061714.
- Takebayashi A., Kimura F., Kishi Y., Ishida M., Takahashi A., Yamanaka A. et al. The association between endometriosis and chronic endometritis. PLoS One. 2014; 9(2): e88354. https://dx.doi.org/10.1371/journal.pone.0088354.
- Yasuo T., Kitaya K. Challenges in clinical diagnosis and management of chronic endometritis. Diagnostics (Basel). 2022; 12(11): 2711. https://dx.doi.org/10.3390/diagnostics12112711.
- Chen C., Song X., Wei W., Zhong H., Dai J., Lan Z. et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat. Commun. 2017; 8(1): 875. https://dx.doi.org/10.1038/s41467-017-00901-0.
- Moreno I., Garcia-Grau I., Perez-Villaroya D., Gonzalez-Monfort M., Bahçeci M., Barrionuevo M.J. et al. Endometrial microbiota composition is associated with reproductive outcome in infertile patients. Microbiome. 2022; 10(1): 1. https://dx.doi.org/10.1186/s40168-021-01184-w.
- Klimaszyk K., Svarre Nielsen H., Wender-Ozegowska E., Kedzia M. Chronic endometritis - is it time to clarify diagnostic criteria? Ginekol. Pol. 2023; 94(2): 152-7. https://dx.doi.org/10.5603/GP.a2022.0147.
- D'Ippolito S., Di Nicuolo F., Pontecorvi A., Gratta M., Scambia G., Di Simone N. Endometrial microbes and microbiome: recent insights on the inflammatory and immune "players" of the human endometrium. Am. J. Reprod. Immunol. 2018; 80(6): e13065. https://dx.doi.org/10.1111/aji.13065.
- Vitagliano A., Laganà A.S., De Ziegler D., Cicinelli R., Santarsiero C.M., Buzzaccarini G. et al. Chronic endometritis in infertile women: impact of untreated disease, plasma cell counts and antibiotic therapy on IVF outcome - a systematic review and meta-analysis. Diagnostics (Basel). 2022; 12(9): 2250. https://dx.doi.org/10.3390/diagnostics12092250.
- Kitaya K., Takeuchi T., Mizuta S., Matsubayashi H., Ishikawa T. Endometritis: new time, new concepts. Fertil. Steril. 2018; 110(3): 344-50. https://dx.doi.org/10.1016/j.fertnstert.2018.04.012.
- Li Q., Li J., Yang K., Peng Y., Xiang Y., Sun S. et al. EBV-positive intravascular large B-cell lymphoma of the liver: a case report and literature review. Diagn. Pathol. 2020; 15(1): 72. https://dx.doi.org/10.1186/s13000-020-00989-x.
- Parks R.N., Kim C.J., Al-Safi Z.A., Armstrong A.A., Zore T., Moatamed N.A. Multiple myeloma 1 transcription factor is superior to CD138 as a marker of plasma cells in endometrium. Int. J. Surg. Pathol 2019; 27(4): 372-9. https://dx.doi.org/10.1177/1066896918814307.
- Cicinelli E., Vitagliano A., Kumar A., Lasmar R.B., Bettocchi S., Haimovich S.; International Working Group for Standardization of Chronic Endometritis Diagnosis. Unified diagnostic criteria for chronic endometritis at fluid hysteroscopy: proposal and reliability evaluation through an international randomized-controlled observer study. Fertil. Steril. 2019; 112(1): 162-173.e2. https://dx.doi.org/10.1016/j.fertnstert.2019.03.004.
- Toson B., Simon C., Moreno I. The endometrial microbiome and its impact on human conception. Int. J. Mol. Sci. 2022; 23(1): 485. https://dx.doi.org/10.3390/ijms23010485.
- Xiong Y., Chen Q., Chen C., Tan J., Wang Z., Gu F., Xu Y. Impact of oral antibiotic treatment for chronic endometritis on pregnancy outcomes in the following frozen-thawed embryo transfer cycles of infertile women: a cohort study of 640 embryo transfer cycles. Fertil. Steril. 2021; 116(2): 413-42. https://dx.doi.org/10.1016/j.fertnstert.2021.03.036.
- Song D., He Y., Wang Y., Liu Z., Xia E., Huang X. et al. Impact of antibiotic therapy on the rate of negative test results for chronic endometritis: a prospective randomized control trial. Fertil. Steril. 2021; 115(6): 1549-56. https://dx.doi.org/10.1016/j.fertnstert.2020.12.019.
- Kitaya K., Yasuo T. Commonalities and disparities between endometriosis and chronic endometritis: therapeutic potential of novel antibiotic treatment strategy against ectopic endometrium. Int. J. Mol. Sci. 2023; 24(3): 2059. https://dx.doi.org/10.3390/ijms24032059.
- Kitaya K., Tanaka S.E., Sakuraba Y., Ishikawa T. Multi-drug-resistant chronic endometritis in infertile women with repeated implantation failure: trend over the decade and pilot study for third-line oral antibiotic treatment. J. Assist. Reprod. Genet. 2022; 39(8): 1839-48. https://dx.doi.org/10.1007/s10815-022-02528-7.
- Zhang Y.Y., Li M.Z., Shen H.H., Abudukeyoumu A., Xie F, Ye J.F. et al. Ginsenosides in endometrium-related diseases: emerging roles and mechanisms. Biomed. Pharmacother. 2023; 166: 115340. https://dx.doi.org/10.1016/j.biopha.2023.115340.
- Локшин В.Н., Аскар Е., Рыбина А.Н., Абшекенова А.Т., Карибаева Ш.К., Валиев Р.К. Опыт применения бовгиалуронидазы азоксимера в комплексном лечении хронического эндометрита у женщин с повторными неудачами имплантации. Акушерство и гинекология. 2023; 5: 108-12. [Lokshin V.N., Askar E., Rybina A.N., Abshekenova A.T., Karibaeva Sh.K., Valiev R.K. Experience with bovhyaluronidase azoximer used in the combination treatment of chronic endometritis in women with repeated implantation failures. Obstetrics and Gynecology. 2023; (5): 108-12. (in Russian)]. https://dx.doi.org/10.18565/aig.2023.119.
Received 10.06.2024
Accepted 17.06.2024
About the Authors
Svetlana O. Dubrovina, Professor, MD, PhD, Chief Researcher at the Obstetrics and Pediatrics Research Institute, Rostov State Medical University, Ministry of Health of Russia; Professor at the Department of Obstetrics and Gynecology No. 1, RostSMU, Ministry of Health of Russia, 344012, Russia, Rostov-on-Don, Mechnikova str., 43, +7(918)558-51-13, s.dubrovina@gmail.com, https://orcid.org/0000-0003-2424-2672Daria M. Bozhinskaya, resident physician, Department of Obstetrics and Gynecology No. 1, Rostov State Medical University, Ministry of Health of Russia, 344022, Russia, Rostov-on-Don, Nakhichevansky per., 29, +7(908)182-74-47, dasha.bozhinskaya@yandex.ru
Vitaly S. Gimbut, MD, PhD, Clinic "9 months", Russia, Rostov-on-Don, Soborny per., 58/7.
Diana Yu. Bogunova, resident physician, Department of Obstetrics and Gynecology No. 1, Rostov State Medical University, Ministry of Health of Russia, 344022, Russia, Rostov-on-Don, Nakhichevansky per., 29, +7(961)524-77-23, bogunovadi@yandex.ru
Nina S. Tsirkunova, Honored Doctor of the Russian Federation, obstetrician-gynecologist of the highest category, Head of the Gynecological Department, City Hospital No. 6 of Rostov-on-Don, 344025, Russia, Rostov-on-Don, Saryan str., 85, +7(928)174-21-94, tsirkunovanina@gmail.com
Kristina G. Tsirkunova, 3rd year student of the Medical and Preventive Faculty, Rostov State Medical University, Ministry of Health of Russia, 344022, Russia, Rostov-on-Don, Nakhichevansky per., 29, +7(928)214-87-79, tsirkunovaaakris@mail.ru
Corresponding author: Svetlana O. Dubrovina, s.dubrovina@gmail.com