Predictors of endometrial polyp recurrence and potential preventive methods

Introduction. Endometrial polyposis is a common gynecological disease, resulting in benign overgrowths of endometrial tissue and being associated with abnormal uterine bleeding, infertility, and recurrent implantation failure. The recurrence rate following polypectomy varies from 14.2 to 45.5 %, leading to repeated intrauterine interventions and posing a significant obstacle to pregnancy achievement. Further research is needed to identify predictors of endometrial polyp recurrence and potential preventive strategies.

Aim: to study and analyze scientific data on endometrial polyps related to underlying pathogenesis, diagnosis, and prevention methods.

Materials and Methods. The literature search was conducted in the electronic databases eLibrary.ru, CyberLeninka, PubMed/ MEDLINE for the period 2015–2025 using keywords and phrases in Russian and English: «endometrial polyps», «pathogenesis», «endometrial polyps recurrence», «polypectomy», «chronic endometritis». Publications reporting original research findings were selected for analysis. The scientific data analysis included various inflammatory markers, their role in predicting endometrial polyp recurrence, and potential preventive measures.

Results. The current scientific concept considers endometrial polyps and chronic endometritis (CE) as stages of a single pathological process resulting from chronic inflammation as evidenced by similarities in dysregulated pathogenetic pathways and the uterine microbiome therein. It has been found that the majority of infertile patients with endometrial polyps show CE signs (51–92.6 %). CE markedly increases a risk of endometrial polyp recurrence post-resection. In addition, a risk of endometrial polyp recurrence correlates with CE severity. However, in most cases, hysteroscopic polypectomy alone was sufficient to treat CE with endometrial polyps without antibiotic therapy. Moreover, inappropriate antibiotic therapy may not only be ineffective but also delay recovery from CE, reduce the efficacy of CE-related polypectomy and increase the frequency of endometrial polyp recurrence. This suggests a need to identify predictors of endometrial polyp recurrence to determine risk groups and optimize management strategies for such patients. Analyzing scientific publications revealed significant differences in the levels of CD138 (plasma cell marker), CD20 (B-cell lymphocyte marker), CD8 (cytotoxic T-cell lymphocyte marker), matrix metalloproteinases, cyclooxygenase 2, and proteins of the Hippo-YAP1 and Wnt signaling pathways in endometrial polyp tissue compared to normal endometrium. Additionally, a decreased and altered uterine microbiota diversity were observed, which may be promising to seek out for markers predicting endometrial polyp recurrence.

Conclusion. The high prevalence and recurrence of endometrial polyps related to chronic endometritis, along with shared pathogenetic mechanisms, suggests that factors associated with CE could may serve as potential predictors of endometrial polyp recurrence. Comprehensively investigated uterine microbiome and factors contributing to endometrial polyp development build up a relevant and promising strategy promoting uncovering related to development of this pathology, optimizing management for patients with endometrial polyp recurrence as well as proposing pathogenesis-driven preventive and therapeutic approaches.

1. Nijkang N.P., Anderson L., Markham R., Manconi F. Endometrial polyps: pathogenesis, sequelae and treatment. SAGE Open Med. 2019;7:2050312119848247. https://doi.org/10.1177/2050312119848247.

2. Islamidi D.K., Belyh N.S., Kovalev V.V., Milyaeva N.M. Contribution of the uterine cavity microbiota to the development of pathological endometrial processes. [Vklad mikrobioty polosti matki v razvitie patologicheskih processov endometriya]. Ural'skij medicinskij zhurnal. 2023;22(1):96– 103. (In Russ.). https://doi.org/10.52420/2071-5943-2023-22-1-96-103.

3. Clinical guidelines – Endometrial polyps – 2023-2024-2025 (25.04.2023). [Klinicheskie rekomendacii – Polipy endometriya – 2023-2024-2025 (25.04.2023)]. Moscow: Ministerstvo zdravoohraneniya Rossijskoj Federacii, 2023. 17 p. (In Russ.). Available at: http://disuria.ru/_ld/12/1289_kr23N84p0MZ.pdf. [Accessed: 15.12.2025].

4. Orazov M.R., Mihaleva L.M., Poimanova O.F. Morphological determinants of recurrent endometrial polyps in women of reproductive age. [Morfologicheskie determinanty recidiviruyushchih polipov endometriya u zhenshchin reproduktivnogo vozrasta]. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie. 2024;12(3):55–60. (In Russ.). https://doi.org/10.33029/2303-9698-2024-12-3-55-60.

5. Huang J., You X., Zhao Z. et al. Chronic endometritis multiplies the recurrence risk of endometrial polyps after transcervical resection of endometrial polyps: a prospective study. BMC Womens Health. 2024;24(1):372. https://doi.org/10.1186/s12905-024-03221-w.

6. Vaduva C.C., Constantinescu C., Serbanescu M. et al. The association between endometrial polyps, chronic endometritis, and IVF outcomes. Eur Rev Med Pharmacol Sci. 2023;27(18):8895–904. https://doi.org/10.26355/eurrev_202309_33810.

7. Sasaki L.M.P., Andrade K.R.C., Figueiredo A.C.M.G. et al. Factors associated with malignancy in hysteroscopically resected endometrial polyps: a systematic review and meta-analysis. J Minim Invasive Gynecol. 2018;25(5):777–85. https://doi.org/10.1016/j.jmig.2018.02.004.

8. Raz N., Feinmesser L., Moore O., Haimovich S. Endometrial polyps: diagnosis and treatment options – a review of literature. Minim Invasive Ther Allied Technol. 2021;30(5):278–87. https://doi.org/10.1080/13645706.2021.1948867.

9. Orazov M.R., Mikhaleva L.M., Poimanova O.F. Management strategy for patients with asymptomatic endometrial polyps associated with chronic endometritis. [Taktika vedeniya pacientok s bessimptomnymi polipami endometriya, associirovannymi s hronicheskim endometritom]. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie. 2025;13(S):87– 93. (In Russ.). https://doi.org/10.33029/2303-9698-2025-13-suppl-87-93.

10. Hashemi M., Madani E.S., Ghahiri A. et al. Assessment of long- and short-term outcomes of hysteroscopic polypectomy in patients with uterine polyps. Adv Biomed Res. 2024;13:57. https://doi.org/10.4103/abr.abr_66_23.

11. Zheng Q.M., Mao H.I., Zhao Y.J. et al. Risk of endometrial polyps in women with endometriosis: a meta-analysis. Reprod Biol Endocrinol. 2015;13:103. https://doi.org/10.1186/s12958-015-0092-2.

12. Ciscato A., Zare S.Y., Fadare O. The significance of recurrence in endometrial polyps: a clinicopathologic analysis. Hum Pathol. 2020;100:38–44. https://doi.org/10.1016/j.humpath.2020.03.005.

13. Lara-Domínguez M.D., Arjona-Berral J.E., Dios-Palomares R., Castelo-Branco C. Outpatient hysteroscopic polypectomy: bipolar energy system (Versapoint®) versus diode laser – randomized clinical trial. Gynecol Endocrinol. 2016;32(3):196–200. https://doi.org/10.3109/09513590.2015.1105209.

14. Liang J., Li M., Zhang L. et al. Analysis of the microbiota composition in the genital tract of infertile patients with chronic endometritis or endometrial polyps. Front Cell Infect Microbiol. 2023;13:1125640. https://doi.org/10.3389/fcimb.2023.1125640.

15. Yan C., Xing C., Wei T. et al. Impact of estrogen and progesterone receptor expression on the incidence of endometrial polyps. Biomark Med. 2023;17(21):881–7. https://doi.org/10.2217/bmm-2023-0411.

16. Chernukha G.E., Asaturova A.V., Ivanov I.A., Korshunov A.A. Hormonal sensitivity of endometrial polyps and the efficiency of LNG-IUD as a method of their secondary prevention. [K voprosu o gormonal'noj chuvstvitel'nosti polipov endometriya i effektivnosti primeneniya LNG-VMS v kachestve metoda vtorichnoj profilaktiki]. Akusherstvo i ginekologiya. 2020;(6):65–71. (In Russ.). https://doi.org/10.18565/aig.2020.6.65-71.

17. Yu X., Kong W., Shang K. et al. Abnormal expression of Hippo-YAP1 signalling pathway and progesterone resistance mechanism in endometrial polyps. J Obstet Gynaecol. 2025;45(1):2533965. https://doi.org/10.1080/01443615.2025.2533965.

18. Jiang R., Yang Y., Huang Q. et al. Immunohistochemical expression of estrogen receptor α, Bcl-2 and NF-κB P65 in the polyps of patients with and without endometriosis. J Obstet Gynaecol Res. 2020;46:1819–26. https://doi.org/10.1111/jog.14370.

19. Li J., Liu L., Fan R. The PKM2/HIF-1α axis is involved in the pathogenesis of endometriosis via TGF-β1 under endometrial polyps. Front Biosci. 2024;29(12):417. https://doi.org/10.31083/j.fbl2912417.

20. Nian J., Zhou Y., Zhu Y. et al. Expression levels of ADAMTS 5, 9, and 12 in endometrial polyps and their predictive value for the diagnosis and recurrence of endometrial polyps. Eur J Obstet Gynecol. 2024;295:86–91. https://doi.org/10.1016/j.ejogrb.2024.02.008.

21. Tsyndrenko N., Lyndі M., Sikora K. et al. ER and COX2 expression in endometrial hyperplasia processes. Medicine. 2023;102(33):e34864. https://doi.org/10.1097/MD.0000000000034864.

22. Tolibova G.H., Tral´ T.G., Kleshchov M.A. et al. Endometrial dysfunction: an algorithm for histological and immunohistochemical studies. [Endometrial'naya disfunkciya: algoritm gistologicheskogo i immunogistohimicheskogo issledovaniya]. Zhurnal akusherstva i zhenskih boleznej. 2015;64(4):69–77. (In Russ.). https://doi.org/10.17816/JOWD64469-77.

23. Kuroda K., Takamizawa S., Motoyama H. et al. Analysis of the therapeutic effects of hysteroscopic polypectomy with and without doxycycline treatment on chronic endometritis with endometrial polyps. Am J Reprod Immunol. 2021;85(6):e13392. https://doi.org/10.1111/aji.13392.

24. Agostinis C., Mangogna A., Bossi F. et al. Uterine immunity and microbiota: a shifting paradigm. Front Immunol. 2019;10:2387. https://doi.org/10.3389/fimmu.2019.02387.

25. Shi Y, Li J, Xie J, Yang T, Ma Q, Chen H, Guo W. Comparison of the lower genital tract microbiome composition in patients with benign gynecological disease. Front Glob Womens Health. 2025;6:1507907. https://doi.org/10.3389/fgwh.2025.1507907.

26. Cao W., Fu X., Zhou J. et al. The effect of the female genital tract and gut microbiome on reproductive dysfunction. Biosci Trends. 2023;17(6):458– 74. https://doi.org/10.5582/bst.2023.0113.

27. Sola-Leyva A., Andrés-León E., Molina N.M. et al. Mapping the entire functionally active endometrial microbiota. Hum Reprod. 2021;36(4):1021–31. https://doi.org/10.1093/humrep/deaa372.

28. Gao H., Lu N., Chen Y. et al. Endometrial microbiome during early pregnancy among women with and without chronic endometritis: a pilot study. Front Cell Infect Microbiol. 2025;15:1615182. https://doi.org/10.3389/fcimb.2025.1615182.

29. Kumar L., Dwivedi M., Jain N. et al. The female reproductive tract microbiota: friends and foe. Life. 2023;13:1313. https://doi.org/10.3390/life13061313.

30. 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. 2019;26(7):1346–50. https://doi.org/10.1016/j.jmig.2019.01.012.

31. Tolibova G.Kh. Endometrial dysfunction in women with infertility: pathogenetic determinants and clinical and morphological diagnostics. [Endometrial'naya disfunkciya u zhenshchin s besplodiem: patogeneticheskie determinanty i kliniko-morfologicheskaya diagnostika: Avtoref. dis... dokt. med. nauk]. Saint Petersburg, 2018. 35 p. (In Russ.).

32. Tral T.G. Morphogenesis of implantation and gravid transformation of the endometrium in patients with chronic endometritis. [Morfogenez implantacii i gravidarnoj transformacii endometriya u pacientok s hronicheskim endometritom: Avtoref. dis... dokt. med. nauk]. Saint Petersburg, 2023. 35 p. (In Russ.).

33. Peng C., Liu J., Ding H. et al. The effect of hysteroscopic endometrial polypectomy combined with LNG-IUS treatment on polyp recurrence: a multicenter retrospective study. Front Surg. 2025;12:1557877. https://doi.org/10.3389/fsurg.2025.1557877.

34. Orazov M.R., Mikhaleva L.M., Poimanova O.F. Effectiveness of treatment of symptomatic endometrial polyps. [Effektivnost' lecheniya simptomnyh endometrial'nyh polipov]. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie. 2025;13(S):37–43. https://doi.org/10.33029/2303-9698-2025-13-suppl-37-43.

35. Dobrokhotova Yu.E., Gankovskaya L.V., Borovkova E.I., Nugumanova O.R. Exogenous cytokine therapy in the treatment of patients with chronic endometritis. [Ekzogennaya tsitokinoterapiya v lechenii patsientok s khronicheskim endometritom]. Akusherstvo i ginekologiya. 2021;(2):119–26. (In Russ.). https://doi.org/10.18565/aig.2021.2.119-126.

36. Pourakbari R., Ahmadi H., Yousefi M., Aghebati-Maleki L. Cell therapy in female infertility-related diseases: Emphasis on recurrent miscarriage and repeated implantation failure. Life Sci. 2020;258:118181. https://doi.org/10.1016/j.lfs.2020.118181.

37. Dikke G.B., Ostromensky V.V. Immune dysfunction in chronic endometritis and the experience of its correction using local cytokine therapy. [Narushenie immunnogo statusa pri khronicheskom endometrite i opyt ego korrektsii posredstvom lokalʹnoj tsitokinoterapii]. Akusherstvo i ginekologiya. 2019;(9):139–46. (In Russ.). https://doi.org/10.18565/aig.2019.9.139-146.

38. Liu Y., Yu X., Huang J. et al. Additional dydrogesterone for the treatment of chronic endometritis treated with antibiotic in premenopausal women with endometrial polyps: a retrospective cohort study. BMC Womens Health. 2022;22(1):435. https://doi.org/10.1186/s12905-022-02033-0.