Эффект «разбросанных пазлов»: имплантационные нарушения при хроническом эндометрите

Радзинский В.Е., Оразов М.Р., Токтар Л.Р. и др. Эффект «разбросанных пазлов»: имплантационные нарушения при хроническом эндометрите. Гинекология. 2020; 22 (6): 93–100. DOI: 10.26442/20795696.2020.6.200493

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Radzinsky V.E., Orazov M.R., Toktar L.R. et al. The scattered puzzle effect: implantation disorders in chronic endometritis. Gynecology. 2020; 22 (6): 93–100. DOI: 10.26442/20795696.2020.6.200493

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Аннотация

Хронический эндометрит (ХЭ) дефинируется как состояние воспаления, локализованного в эндометрии, сопровождающегося отеком, диссоциированным созреванием эпителиоцитов и фибробластов, повышенной плотностью стромы и наличием в ней плазматического клеточного инфильтрата. Особого внимания заслуживает связь хронического воспаления в эндометрии с бесплодием. Неадекватный ответ иммунокомпетентных клеток эндометрия, включая нарушенный синтез провоспалительных цитокинов, дисрецептивность, расстройство процессов пролиферации и дифференцировки – главные звенья формирования бесплодия у пациенток с ХЭ. Несмотря на то, что наличие нормоценоза полости матки сегодня не вызывает сомнений – это физиологическая норма, персистирующую бактериальную инфекцию эндометрия до сих пор называют основным этиопатогенетическим фактором ХЭ и, значит, главной точкой приложения терапевтических средств. Тем не менее в ряде работ подчеркнута особая роль не бактериальной, а вирусной этиологии эндометрита, особенно в контексте развивающейся на этом фоне инфертильности. Кажется, что роль вирусной инфекции эндометрия в развитии неблагоприятных исходов беременности и программ экстракорпорального оплодотворения недооценена. Необходимы дальнейшие исследования, чтобы уточнить связь вирусной инфекции как триггера имплантационной несостоятельности у бесплодных женщин с ХЭ.

Ключевые слова: хронический эндометрит, вирусы, бесплодие, неудачи имплантации.

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Chronic endometritis (CE) is defined as a state of inflammation localized in the endometrium, accompanied by edema, dissociated maturation of epithelial cells and fibroblasts, increased stromal density and the presence of plasma cell infiltrate in it. The connection between chronic inflammation in the endometrium and infertility deserves special attention. Inadequate response of immunocompetent endometrial cells, including impaired synthesis of proinflammatory cytokines, dysreceptiveness, disorders of proliferation and differentiation processes are the main links in the formation of infertility in patients with CE. Despite the fact that the presence of a normocenosis of the uterine cavity today is not in doubt – this is a physiological norm, persistent bacterial infection of the endometrium is still called the main etiopathogenetic factor of CE and, therefore, the main point of application of therapeutic agents. Nevertheless, a number of works have emphasized the special role of not bacterial, but viral etiology of endometritis, especially in the context of infertility developing against this background. It seems that the role of viral endometrial infection in adverse pregnancy outcomes and in vitro fertilization programs is underestimated. Further research is needed to clarify the relationship of viral infection as a trigger of implantation failure in infertile women with CE.

Key words: chronic endometritis, viruses, infertility, implantation failure.

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Список литературы

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1. Kimura F, Takebayashi A, Ishida M et al. Review: Chronic endometritis and its effect on reproduction. J Obstet Gynaecol Res 2019; 45 (5): 951–60. DOI: 10.1111/jog.13937
2. Puente E, Alonso L, Laganà AS et al. Chronic Endometritis: Old Problem, Novel Insights and Future Challenges. Int J Fertil Steril 2020; 13 (4): 250–6. DOI: 10.22074/ijfs.2020.5779
3. Drizi A, Djokovic D, Laganà AS, van Herendael B. Impaired inflammatory state of the endometrium: a multifaceted approach to endometrial inflammation. Current insights and future directions. Prz Menopauzalny 2020; 19 (2): 90–100. DOI: 10.5114/pm.2020.97863
4. Song D, Feng X, Zhang Q et al. Prevalence and confounders of chronic endometritis in premenopausal women with abnormal bleeding or reproductive failure. Reprod Biomed Online 2018; 36: 78–83. DOI: 10.1016/j.rbmo.2017.09.008
5. Mikhalev S.A., Babichenko I.I., Shakhpazyan N.K. et al. The role of urogenital infection in the development of spontaneous preterm birth. Reproduction problems. 2019; 25 (2): 93–9. DOI: 10.17116 /repro20192502193 (in Russian).
6. Cicinelli E, Matteo M, Trojano G et al. Chronic endometritis in patients with unexplained infertility: Prevalence and effects of antibiotic treatment on spontaneous conception. Am J Reprod Immunol 2018; 79. DOI: 10.1111/aji.12782
7. Zargar M, Ghafourian M Nikbakht R et al. Evaluating Chronic Endometritis in Women with Recurrent Implantation Failure and Recurrent Pregnancy Loss by Hysteroscopy and Immunohistochemistry. J Minim Invasive Gynecol 2020; 27 (1): 116–21. DOI: 10.1016/j.jmig.2019.02.016
8. Liu Y, Chen X, Huang J et al. Comparison of the prevalence of chronic endometritis as determined by means of different diagnostic methods in women with and without reproductive failure. Fertil Steril 2018; 109: 832–9. DOI: 10.1016/j.fertnstert.2018.01.022
9. Cicinelli E, Trojano G, Mastromauro M et al. Higher prevalence of chronic endometritis in women with endometriosis: a possible etiopathogenetic link. Fertil Steril 2017; 108 (2): 289–295.e1. DOI: 10.1016/j.fertnstert.2017.05.016
10. Cicinelli E, Bettocchi S, de Ziegler D et al. Chronic endometritis, a common disease hidden behind endometrial polyps in premenopausal women: first evidence from a case-control study. J Minim Invasive Gynecol. Published Online: January 29, 2019. DOI: 10.1016/j.jmig.2019.01.012
11. Peric A, Weiss J, Vulliemoz N et al. Bacterial Colonization of the Female Upper Genital Tract. Int J Mol Sci 2019; 20 (14): 3405. DOI: 10.3390/ijms20143405
12. Hansen LK, Becher N, Bastholm S et al. The cervical mucus plug inhibits, but does not block, the passage of ascending bacteria from the vagina during pregnancy. Acta Obstet Gynecol Scand 2014; 93: 102–8. DOI: 10.1111/aogs.12296
13. Chen C, Song X, Wei W et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun 2017; 8: 875. DOI: 10.1038/s41467-017-00901-0
14. Molina NM, Sola-Leyva A, Saez-Lara MJ et al. New Opportunities for Endometrial Health by Modifying Uterine Microbial Composition: Present or Future? Biomolecules 2020; 10 (4): 593. DOI: 10.3390/biom10040593
15. Lax SF. Endometritis: Rare disease with clinical importance? Pathologe 2016; 37 (6): 521–5. DOI: 10.1007/s00292-016-0237-x
16. Marci R, Gentili V, Bortolotti D et al. Presence of HHV-6A in Endometrial Epithelial Cells from Women with Primary Unexplained Infertility. PLoS One 2016; 11 (7): e0158304. DOI: 10.1371/journal.pone.0158304
17. Komaroff AL, Phan T, Flamand L, Pellett PE. Summary of the 9th international conference on human herpesviruses 6 and 7 (HHV-6A, HHV-6B, and HHV-7). J Med Virol 2016; 88 (12): 2038–43. DOI: 10.1002/jmv.24561
18. Coulam CB, Bilal M, Salazar Garcia MD et al. Prevalence of HHV-6 in endometrium from women with recurrent implantation failure. Am J Reprod Immunol 2018; 80 (1): e12862. DOI: 10.1111/aji.12862
19. Mamedalieva NM, Kurmanova AM, Moshkalova GN, Kim V. Local immunity status in patients with miscarriages and herpetic infection. Gynecol Endocrinol 2016; 32 (Suppl. 2): 45–6. DOI: 10.1080/09513590.2016.1232772
20. Mikhaleva L.M., Boltovskaya M.N., Mikhalev S.A. et al. Endometrial dysfunction caused by chronic endometritis: сlinical and morphological aspects. Arkhiv patologii. 2017; 79 (6): 22–9. DOI: 10.17116/patol201779622-29 (in Russian).
21. Proshin S.N., Glushakov R.I., Semenova I.V. et al. Clinical and immunological efficiency of sodium nucleospermate in treating chronic endometritis and infertility complicated by HPV infection. Eksperimental'naia i klinicheskaia farmakologiia. 2013; 76 (3): 27–30. DOI: 10.30906/0869-2092-2013-76-3-27-30 (in Russian).
22. Sfakianoudis K, Simopoulou M, Nikas Y et al. Efficient treatment of chronic endometritis through a novel approach of intrauterine antibiotic infusion: a case series. BMC Womens Health 2018; 18: 197. DOI: 10.1186/s12905-018-0688-8
23. 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
24. Orazov M.R., Mikhaleva L.M., Semenov P.A. Chronic endometritis: pathogenesis, diagnosis, management and associated infertility. Klinicheskaia i eksperimental'naia morfologiia. 2020; 9 (2): 16–25. DOI: 10.31088/CEM2020.9.2.16-25 (in Russian).
25. Fukui A, Funamizu A, Fukuhara R, Shibahara H. Expression of natural cytotoxicity receptors and cytokine production on endometrial natural killer cells in women with recurrent pregnancy loss or implantation failure, and the expression of natural cytotoxicity receptors on peripheral blood natural killer cells in pregnant women with a history of recurrent pregnancy loss. J Obstet Gynaecol Res 2017; 43 (11): 1678–86. DOI: 10.1111/jog.13448
26. Nazarenko TA, Kalinina EA, Knyazeva EA et al. The role of abnormal hypermethylation of the HOXA10 and HOXA11 promoters in implantation failures in IVF programs. Gynecol Endocrinol 2019; 35 (Suppl. 1): 31–4. DOI: 10.1080/09513590.2019.1632087
27. Negishi Y, Shima Y, Takeshita T, Morita R. Harmful and beneficial effects of inflammatory response on reproduction: sterile and pathogen-associated inflammation. Immunol Med 2020; p. 1–18. DOI: 10.1080/25785826.2020.1809951
28. Cicinelli E, Vitagliano A, Kumar A et al. 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): 162–73e2. DOI: 10.1016/j.fertnstert.2019.03.004
29. Kitaya K, Matsubayashi H, Yamaguchi K et al. Chronic endometritis: potential cause of infertility and obstetric and neonatal complications. Am J Reprod Immunol 2016; 75 (1): 13–22.
30. Sfakianoudis K, Simopoulou M, Nitsos N et al. Successful Implantation and Live Birth Following Autologous Platelet-rich Plasma Treatment for a Patient with Recurrent Implantation Failure and Chronic Endometritis. In Vivo 2019; 33 (2): 515–21. DOI: 10.21873/invivo.11504
31. Vitagliano A, Saccardi C, Litta PS, Noventa M. Chronic endometritis: really so relevant in repeated IVF failure? Am J Reprod Immunol 2017; 78. DOI: 10.1111/aji.12758
32. Kitaya K, Matsubayashi H, Takaya Y et al. Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure. Am J Reprod Immunol 2017; 78: e12719. DOI: 10.1111/aji.12719
33. Canumalla SA, Blakemore JK, Grifo J, Keefe D. What is the most effective treatment for endometritis in women undergoing assisted reproductive technology? Fertil Steril 2019; 112. DOI: 10.1016/j.fertnstert.2019.07.961
34. Vitagliano A, Saccardi C, Noventa M 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. DOI: 10.1016/j.fertnstert.2018.03.017
35. Zhang Y, Xu H, Liu Y et al. Confirmation of chronic endometritis in repeated implantation failure and success outcome in IVF-ET after intrauterine delivery of the combined administration of antibiotic and dexamethasone. Am J Reprod Immunol 2019; 82 (5): e13177. DOI: 10.1111/aji.13177
36. Koreeva N.V., Dobrohotova Ju.Je. Lokal'naja citokinoterapija v ginekologicheskoj praktike (obzor literatury). Problemy reprodukcii. 2013;4: 21–6 (in Russian).
37. Mal'ceva L.I., Smolina G.R., Sharipova R.I. et al. Hronicheskij jendometrit v praktike akushera-ginekologa. Ros. vestn. akushera-ginekologa. 2015; 5: 102–5 (in Russian).
38. Dikke G.B., Ostromenskij V.V. Narushenie immunnogo statusa pri hronicheskom jendometrite i opyt ego korrekcii posredstvom lokal'noj citokinoterapii. Akusherstvo i ginekologija. 2019; 9: 139–46. DOI: 10.18565/aig.2019.9.139-146 (in Russian).
39. Dobrohotova Ju.Je., Gankovskaja L.V., Borovkova E.I. et al. Modulirovanie lokal'noj jekspressii faktorov vrozhdennogo immuniteta u pacientok s hronicheskim jendometritom i besplodiem. Akusherstvo i ginekologija. 2019; 5: 125–32. DOI: 10.18565/aig.2019.5.125-132 (in Russian).

Авторы

В.Е. Радзинский1, М.Р. Оразов*1, Л.Р. Токтар1, Л.М. Михалева2, П.А. Семенов1, Р.Е. Орехов1, Е.В. Лагутина1, Е.С. Силантьева3

1 ФГАОУ ВО «Российский университет дружбы народов», Москва, Россия;
2 ФГБНУ «Научно-исследовательский институт морфологии человека», Москва, Россия;
3 Клинический госпиталь «Лапино», д. Лапино, Московская область, Россия
*omekan@mail.ru

________________________________________________

Victor E. Radzinsky1, Mekan R. Orazov*1, Liliia R. Toktar1, Liudmila M. Mihaleva2, Pavel A. Semenov1, Roman E. Orehov1, Elena V. Lagutina1, Elena S. Silantyeva3

1 People’s Friendship University of Russia, Moscow, Russia;
2 Research Institute of Human Morphology, Moscow, Russia;
3 Clinical Hospital "Lapino", v. Lapino, Moscow region, Russia
*omekan@mail.ru

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