New treatment options for chronic endometritis

Mekan R. Orazov , Viktor E. Radzinskiy , Liudmila M. Mikhaleva , Elena S. Silantyeva , Roman E. Orekhov , Irina A. Mullina , Rina Yu. Mitrelis , Svetlana V. Ivanova

For citation:

Abstract

Chronic inflammation disturbs endometrial cyclic biotransformation and receptivity, which are of key importance for successful implantation of the embryo and determine the clinical significance of this disease entity for reproductive medicine. Today, the chronic endometritis diagnosis efficacy and pathogenetic therapy selection remain the issues that are still relevant. The necessity of using bovhyaluronidase azoximer in combination treatment regimens for chronic endometritis has been proven. The use of bovhyaluronidase azoximer in a dose of 3000 IU once every 3 days for a month reduces dysmenorrhea severity, improves local hemodynamics at the level of uterine blood vessels, significantly decreases the inflammatory marker expression, up to complete elimination.

Keywords: chronic endometritis, chronic inflammation, receptivity, bovhyaluronidase azoximer.

References

1. Серебренникова К.Г., Арутюнян Н.А., Алексин А.И. Диагностика и клинические критерии хронического эндометрита. Гинекология. 2018;20(6):53-9. DOI: 10.26442/20795696.2018.6.180070

Serebrennikova K.G., Arutyunyan N.A., Aleksin A.I. Diagnostics and clinical criteria of chronic endometritis. Gynecology. 2018; 20(6):53–9. DOI: 10.26442/20795696.2018.6.180070 (in Russian).

2. Воспалительные болезни женских тазовых органов. Клинические рекомендации Минздрава России. М.: Российское общество акушеров-гинекологов, 2024.

Inflammatory diseases of the female pelvic organs. Clinical guidelines of the Russian Ministry of Health. Moscow: Russian Society of Obstetricians and Gynecologists, 2024 (in Russian).

3. Прегравидарная подготовка. Клинический протокол МАРС. Версия 3.0. М.: StatusPraesens, 2023.

Preconception Preparation. MARS Clinical Protocol. Version 3.0. Moscow: StatusPraesens, 2023 (in Russian).

4. Cicinelli E, Cicinelli R, Vitagliano A. Antibiotic therapy for chronic endometritis and its reproductive implications: a step forward, with some uncertainties. Fertil Steril 2021;115(6):1445-6. DOI: 10.1016/j.fertnstert.2021.03.025

5. Lee H, Kim J, Choi D et al. Chronic endometritis prevalence, associated factors and pregnancy outcome among infertile women. Hum Reprod 2024;39(Suppl.1):deae108.684. DOI: 10.1093/humrep/deae108.684

6. Bouet PE, El Hachem H, Monceau E et al. Chronic endometritis in women with recurrent pregnancy loss and recurrent implantation failure: prevalence and role of office hysteroscopy and immunohistochemistry in diagnosis. Fertil Steril 2016;105(1):106-10. DOI: 10.1016/j.fertnstert.2015.09.025

7. Ticconi C, Di Simone N, Campagnolo L et al. Chronic endometritis and recurrent reproductive failure: a systematic review and meta-analysis. Front Immunol 2024;(15):1427454. DOI: 10.3389/fimmu. 2024.1427454

8. Cicinelli E, Resta L, Loizzi V et al. Antibiotic therapy versus no treatment for chronic endometritis: a case-control study. Fertil Steril 2021;115(6):1541-8. DOI: 10.1016/j.fertnstert.2021.01.018

9. Di Pasqua A, Galimberti A, Capitanio E et al. Chronic endometritis in infertile patients: diagnosis, treatment and follow-up. Hum Reprod 2025;40(Suppl.1):deaf097.630. DOI: 10.1093/humrep/deaf097.630

10. Liu L, Yang H, Guo Y et al. The impact of chronic endometritis on endometrial fibrosis and reproductive prognosis in patients with moderate and severe intrauterine adhesions: a prospective cohort study. Fertil Steril 2019;111(5):1002-1010.e2. DOI: 10.1016/j.fertnstert.2019.01.006

11. Локшин В.Н., Кущенко И.Н., Боровиков И.О. и др. Хронический эндометрит и инфертильность – исходы ЭКО (систематический обзор и метаанализ). Кубанский научный медицинский вестник. 2023;30(5):15-40. DOI: 10.25207/1608-6228-2023-30-5-15-40

Lokshin V.N., Kushchenko I.N., Borovikov I.O. et al. Chronic endometritis and infertility – IVF outcomes (systematic review and meta-analysis). Kuban Scientific Medical Bulletin. 2023; 30(5):15–40. DOI: 10.25207/1608-6228-2023-30-5-15-40 (in Russian).

12. McQueen DB, Perfetto CO, Hazard FK, Lathi RB. Pregnancy outcomes in women with chronic endometritis and recurrent pregnancy loss. Fertil Steril 2015;104(4):927-31. DOI: 10.1016/j.fertnstert.2015.06.044

13. Liu L, Yang H, Guo Y et al. The impact of chronic endometritis on endometrial fibrosis and reproductive prognosis. Fertil Steril 2019;111(5):1002-1010.e2.

14. Kuroda K, Ikemoto Y, Ochiai A et al. Prevalence of and risk factors for chronic endometritis in patients with intrauterine disorders after hysteroscopic surgery. Fertil Steril 2022;118(3):568-75. DOI: 10.1016/j.fertnstert.2022.06.013

15. Kalaitzopoulos DR, Samartzis N, Daniilidis A et al. Chronic Endometritis and Endometriosis: Two Sides of the Same Coin? Reprod Sci 2025. DOI: 10.1007/s43032-025-01785-y

16. Cicinelli E, Matteo M, Tinelli R et al. Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment. Reprod Sci 2014;21(5):640-7.

17. Cicinelli E, Di Gennaro F, Gesario A et al. Unified diagnostic criteria for chronic endometritis at fluid hysteroscopy. Fertil Steril 2019;112(1):162-173.e2. DOI: 10.1016/j.fertnstert.2019.03.004

18. Furui M, Ito A, Fukuda Y et al. Endometrial congestion is the only hysteroscopic finding indicative of chronic endometritis. PLoS ONE 2024;19(6):e0303041. DOI: 10.1371/journal.pone.0303041

19. Moreno I, Cicinelli E, Garcia-Grau I et al. The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study. Am J Obstet Gynecol 2018;218(6):602.e1-602.e16. DOI: 10.1016/j.ajog.2018.02.012

20. Kitaya K, Takeuchi T, Mizuta S et al. Endometritis: new time, new concepts. Fertil Steril 2018;110(3):344-50. DOI: 10.1016/j.fertnstert.2018.04.012

21. Yoneda E, Kim S, Tomita K et al. Evaluation of Lipopolysaccharide and Interleukin-6 as Useful Screening Tool for Chronic Endometritis. Int J Mol Sci 2024;25(4):2017. DOI: 10.3390/ijms25042017

22. Zeng S, Liang Y, Li Y et al. Research update for the immune microenvironment of chronic endometritis. J Reprod Immunol 2022;(152):103637. DOI: 10.1016/j.jri.2022.103637

23. Travaglino A, Raffone A, Saccone G et al. The Role of Plasma Cells as a Marker of Chronic Endometritis: A Systematic Review and Meta-Analysis. Biomedicines 2023;11(6):1714. DOI: 10.3390/biomedicines11061714

24. Liu Y, Zhao Z, Jiang X et al. Doxycycline vs levofloxacin combined with tinidazole for treating chronic endometritis: a randomized controlled trial. Am J Obstet Gynecol 2025;S0002937825005253. DOI: 10.1016/j.ajog.2025.07.045

25. Yan X, Zhang Y, Zhang L et al. The pathogenesis, diagnosis, and treatment of chronic endometritis: a comprehensive review. Front Endocrinol 2025;(16):1603570. DOI: 10.3389/fendo.2025.1603570

26. HogenEsch E, Franasiak JM. Chronic endometritis treatment. Fertil Steril 2023;120(3 Pt 1):456-64.

27. Song D, He Y, Wang Y 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. DOI: 10.1016/j.fertnstert.2020.12.019

28. Kitaya K, Matsubayashi H, Takaya Y et al. Clinical background affecting pregnancy outcome following local endometrial injury in infertile patients with repeated implantation failure. Am J Reprod Immunol 2017;78(5):e12727. DOI: 10.1111/aji.12719

29. Cicinelli E, Resta L, Nicoletti R et al. Endometrial micropolyps at fluid hysteroscopy suggest the existence of chronic endometritis. Hum Reprod 2005;20(5):1386-9.

30. Cicinelli E, Di Gennaro F, Gesario A et al. Increasing Antimicrobial Resistance to First-Line Therapies in Chronic Endometritis: A 2020–2024 Cross-Sectional Study. J Clin Med 2025;14(14):4873. DOI: 10.3390/jcm14144873

31. Khalenko V, Obedkova KV, Tapilskaya NI et al. New Approaches to the Treatment of Chronic Endometritis. Hum Reprod 2025;40(Suppl.1):deaf097.196. DOI: 10.1093/humrep/deaf097.196

32. Zhylkova E, Feskov O, Konoplya L et al. Administration of umbilical cord blood and placenta in the treatment of chronic endometritis. Hum Reprod 2025;40(Suppl.1):deaf097.207. DOI: 10.1093/humrep/deaf097.207

33. Di Gennaro F, Cicinelli R, Saracino A et al. Chronic Endometritis and Antimicrobial Resistance: Towards a Multidrug-Resistant Endometritis? Microorganisms 2025;13(1):197. DOI: 10.3390/microorganisms13010197

34. Оразов М.Р., Михалева Л.М., Семенов П.А. Хронический эндометрит: патогенез, диагностика, лечение и его связь с бесплодием. Клиническая и экспериментальная морфология. 2020;9(2):16-25. DOI: 10.31088/CEM2020.9.2.16-25

Orazov M.R., Mikhaleva L.M., Semenov P.A. Chronic endometritis: pathogenesis, diagnosis, treatment, and its relationship with infertility. Clinical and experimental morphology. 2020; 9 (2): 16–25. DOI: 10.31088/CEM2020.9.2.16–25 (in Russian).

35. Wang X, Liu X, Li X et al. Exploring the Relationship between Hyaluronic Acid Size and Biological Activity: A Review. DOI: 10.2139/ssrn.5090479

36. Lu J, Zhao Z, Pan L et al. Hyaluronidase: structure, mechanism of action, diseases and therapeutic targets. Mol Biomedicine 2025;(6):50. DOI: 10.1186/s43556-025-00299-y

37. Тризна Е.Ю., Байдамшина Д.Р., Каюмов А.Р. Влияние in vitro изолированного и сочетанного с антибактериальными средствами применения бовгиалуронидазы азоксимера на целостность бактериальной биопленки. Экспериментальная и клиническая фармакология. 2020;83(2):38-44.

Trizna E.Yu., Baidamshina D.R., Kayumov A.R. Effect of in vitro use of bovhyaluronidase azoximer alone and in combination with antibacterial agents on the integrity of bacterial biofilm. Experimental and Clinical Pharmacology. 2020;83(2):38-44. (in Russian).

38. Тапильская Н.И., Копылова А.А., Будиловская О.В. и др. Оценка эффективности применения бовгиалуронидазы азоксимера в лечении хронического эндометрита у женщин с неудачами имплантации. Женская клиника. 2020;(2):66-72.

Tapilskaya N.I., Kopylova A.A., Budilovskaya O.V. et al. Evaluation of the effectiveness of bovhyaluronidase azoximer in the treatment of chronic endometritis in women with implantation failures. Women's Clinic. 2020;(2):66-72 (in Russian).

39. Радзинский В.Е., Оразов М.Р., Михалева Л.М. и др. Эффективность и безопасность бовгиалуронидазы азоксимера в терапии хронического эндометрита: результаты открытого сравнительного рандомизированного контролируемого исследования Life Cradle. Клинический разбор в общей медицине. 2025;6(12).

Radzinskiy V.E., Orazov M.R., Mikhaleva L.M. et al. Efficacy and safety of bovhyaluronidase azoximer in the treatment of chronic endometritis: results of an open, comparative, randomized, controlled trial Life Cradle. Clinical review for general practice. 2025;6(12) (in Russian).

For citation:Orazov M.R., Radzinskiy V.E., Mikhaleva L.M., Silantyeva E.S., Orekhov R.E., Mullina I.A., Mitrelis R.Yu., Ivanova S.V. New treatment options for chronic endometritis. Clinical review for general practice. 2026; 7 (2): 18–22 (In Russ.). DOI: 10.47407/kr2026.7.2.00765

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Clinical review for general practice