Chronic endometritis – a constantly discussed issue in infertile women

Czech version

Authors: Kryštof Břečka ¹; Borek Sehnal ¹ ; Kateřina Maxová ¹ ; Michael Jiří Halaška ¹ ; Kristýna Keprtová ¹; Martin Hruda ¹ ; Lukáš Rob ¹ ; Tonko Mardešič ²
Authors‘ workplace: Gynekologicko-porodnická klinika 3. LF UK a FNKV, Praha ¹; Sanatorium Pronatal, Praha ²
Published in: Ceska Gynekol 2024; 89(3): 230-236
Category:
doi: https://doi.org/10.48095/cccg2024230

Overview

Objective: A review of current knowledge on the pathophysiology, diagnostic and treatment options for chronic endometritis in infertile women. Methods and results: One of the major causes of failed in vitro fertilization (IVF) is undiagnosed intrauterine pathologies, including chronic inflammation of the uterine mucosa – chronic endometritis. However, some authors relativize the negative impact of chronic endometritis on reproductive outcomes. The etiopathogenesis of chronic endometritis is due to qualitative and quantitative changes in the endometrial microbiome with abnormal multiplication of microorganisms naturally occurring in the uterine cavity or vagina. There is no uniform consensus on the most common pathogen causing chronic endometritis. It is characterized by infiltration of plasma cells into the endometrial stroma outside the menstrual cycle, accompanied by hyperaemia and endometrial oedema. Clinical symptoms are very mild or absent. The diagnosis of chronic endometritis is often difficult because there is no specific clinical or laboratory diagnostic method. The following investigative options are commonly used for the diagnosis of chronic endometritis: diagnostic hysteroscopy, histopathological examination of the endometrium including CD 138 immunohistochemistry and culture from the uterine cavity. However, standardised international hysteroscopic and histopathological criteria for accurate diagnosis of chronic endometritis are still lacking. Empirically administered antibiotic therapy improves the success rate of pregnancy and delivery of a viable foetus in infertile patients with proven chronic endometritis. In addition to reviewing the current knowledge of chronic endometritis, this article discusses the importance of hysteroscopy in the diagnostic process. Conclusion: Chronic endometritis is often a clinically silent disease with negative impact on reproduction in infertile women. Although there are still many unresolved issues, the introduction of hysteroscopy into the diagnostic process is important for clinical practice; however, hysteroscopy even in combination with histological examination of the endometrium, often does not allow an unequivocal diagnosis of chronic endometritis. Further prospective randomised studies in a selected group of women with proven chronic endometritis and repeated failure to implant proven euploid embryos should refine this knowledge.

Keywords:

infertility – Plasma cells – hysteroscopy – antibiotics – chronic endometritis – CD 138 immunohistochemistry – reproductive outcome

Sources

1. Emingr M, Halaj M, Malčák M et al. Intrauterinní adheze a jejich prevence. Ceska Gynekol 2023; 88 (3): 210–213. doi: 10.48095/cccg2023210.

2. Kitaya K, Takeuchi T, Mizuta S et al. Endometritis: new time, new concepts. Fertil Steril 2018; 110 (3): 344–350. doi: 10.1016/j.fertnstert.2018. 04.012.

3. Liu H, Song J, Zhang F et al. A new hysteroscopic scoring system for diagnosing chronic endometritis. J Minim Invasive Gynecol 2020; 27 (5): 1127–1132. doi: 10.1016/j.jmig.2019.08.035.

4. 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.e2–173.e2. doi: 10.1016/j.fertnstert. 2019.03.004.

5. Puente E, Alonso L, Laganà AS et al. Chronic endometritis: old problem, novel insights and future challenges. Int J Fertil Steril 2020; 13 (4): 250–256. doi: 10.22074/ijfs.2020.5779.

6. Gu J, Sun Q, Qi Y et al. The effect of chronic endometritis and treatment on patients with unexplained infertility. BMC Womens Health 2023; 23 (1): 345. doi: 10.1186/s12905-023- 02499-6.

7. de Arruda Veiga EC, Soares Junior JM, Samama M et al. Chronic endometritis and assisted reproduction: a systematic review and meta-analysis. Rev Assoc Medica Bras (1992) 2023; 69 (10): e20230792. doi: 10.1590/1806-9282.202 30792.

8. Pérez-Cejuela BA, Vitale SG, Pérez-Medina T et al. Hysteroscopic versus histopathological agreement in the diagnosis of chronic endometritis: results from a retrospective observational study. Arch Gynecol Obstet 2023; 308 (6): 1817–1822. doi: 10.1007/s00404-023- 07163-w.

9. Singh N, Sethi A. Endometritis – diagnosis, treatment and its impact on fertility – a scoping review. JBRA Assist Reprod 2022; 26 (3): 538–546. doi: 10.5935/1518-0557.20220015.

10. Yasuo T, Kitaya K. Challenges in clinical diagnosis and management of chronic endometritis. Diagnostics (Basel) 2022; 12 (11): 2711. doi: 10.3390/diagnostics12112711.

11. Vitagliano A, Laganà AS, De Ziegler D et al. Chronic endometritis in infertile women: impact of untreated disease, plasma cell count and antibiotic therapy on IVF outcome – a systematic review and meta-analysis. Diagnostics (Basel) 2022; 12 (9): 2250. doi: 10.3390/ diagnostics 12092250.

12. Cicinelli E, Matteo M, Tinelli R et al. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod 2015; 30 (2): 323–330. doi: 10.1093/humrep/ deu292.

13. Kimura F, Takebayashi A, Ishida M et al. Review: chronic endometritis and its effect on reproduction. J Obstet Gynaecol Res 2019; 45 (5): 951–960. doi: 10.1111/jog.13937.

14. Moreno I, Cicinelli E, Garcia-Grau I et al. The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology. Am J Obstet Gynecol 2018; 218 (6): 602.e1–602.e16. doi: 10.1016/j.ajog.2018.02.012.

15. Vaduva CC, Sandulescu MS, Tenovici M et al. Results of in vitro fertilization after diagnosis and treatment of chronic endometritis. Eur Rev Med Pharmacol Sci 2023; 27 (3): 1069–1076. doi: 10.26355/eurrev_202302_31203.

16. Kovář P, Daňková Kučerová J, Dvořáčková J et al. Atlas panoramatické hysteroskopie. 1.vyd. Praha: Maxdorf 2017: 107–113.

17. Di Pietro C, Cicinelli E, Guglielmino MR et al. Altered transcriptional regulation of cytokines, growth factors, and apoptotic proteins in the endometrium of infertile women with chronic endometritis. Am J Reprod Immunol 2013; 69 (5): 509–517. doi: 10.1111/aji.12076.

18. Pinto V, Matteo M, Tinelli R et al. Altered uterine contractility in women with chronic endometritis. Fertil Steril 2015; 103 (4): 1049–1052. doi: 10.1016/j.fertnstert.2015. 01.007.

19. Song D, Li TC, Zhang Y et al. Correlation between hysteroscopy findings and chronic endometritis. Fertil Steril 2019; 111 (4): 772–779. doi: 10.1016/j.fertnstert.2018.12.007.

20. Gkrozou F, Tsonis O, Dimitriou E et al. In women with chronic or subclinical endometritis is hysteroscopy suitable for setting the diagnosis? A systematic review. J Obstet Gynaecol Res 2020; 46 (9): 1639–1650. doi: 10.1111/ jog.14360.

21. Klimaszyk K, Svarre Nielsen H, Wender-Ozegowska E et al. Chronic endometritis – is it time to clarify diagnostic criteria? Ginekol Pol 2023; 94 (2): 152–157. doi: 10.5603/GP.a2022. 0147.

22. Cheng X, Huang Z, Xiao Z et al. Does antibiotic therapy for chronic endometritis improve clinical outcomes of patients with recurrent implantation failure in subsequent IVF cycles? A systematic review and meta-analysis. J Assist Reprod Genet 2022; 39 (8): 1797–1813. doi: 10.1007/s10815-022-02558-1.

23. 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): 1445–1446. doi: 10.1016/j.fertnstert. 2021.03.025.

24. 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. doi: 10.1111/ aji.13392.

25. Trávník P, Ješeta M, Hűttelová R et al. Asistovaná aktivace oocytů. Ceska Gynekol 2023; 88 (6): 459–462. doi: 10.48095/cccg2023459.

26. Vodička J, Dvořan M, Smékalová K et al. Možnosti přípravy endometria ke kryoembryotransferu. Ceska Gynekol 2018; 83 (1): 24–28.

27. Ventruba P, Žáková J, Ješeta M et al. Aspekty výběru embryí a jejich příprava pro vznik lidských embryonálních kmenových buněk určených k humánní terapii. Ceska Gynekol 2021; 86 (1): 5–10. doi: 10.48095/cccg 20215.

28. Dostálová A, Güell F. Motives of patients crossing borders to pursue assisted reproduction – why the Czech Republic is a frequent choice for egg donation treatment. Ceska Gynekol 2022; 87 (2): 137–143. doi: 10.48095/cccg 2022137.

29. Carvalho FM, Aguiar FN, Tomioka R et al. Functional endometrial polyps in infertile asymptomatic patients: a possible evolution of vascular changes secondary to endometritis. Eur J Obstet Gynecol Reprod Biol 2013; 170 (1): 152–156. doi: 10.1016/j.ejogrb.2013. 05.012.

30. Volodarsky-Perel A, Badeghiesh A, Shrem G et al. Prevalence of chronic endometritis in patients with endometrial polyps and unexplained infertility. Fertil Steril 2019; 112 (3): e332. doi: 10.1016/j.fertnstert.2019. 07.960.

31. Vitagliano A, Cialdella M, Cicinelli R et al. Association between endometrial polyps and chronic endometritis: is it time for a paradigm shift in the pathophysiology of endometrial polyps in pre-menopausal women? Results of a systematic review and meta-analysis. Diagnostics (Basel) 2021; 11 (12): 2182. doi: 10.3390/diagnostics11122182.

32. Mokrá V, Petr I, Soukeník J. Význam ultrazvukově asistované hydrolaparoskopie v rozhodovacím algoritmu péče o neplodný pár. Výsledky Centra asistované reprodukce Gennet Liberec 2012–2013. Ceska Gynekol 2014; 79 (3): 226–230.

33. Kovář P. Hysteroskopie v ambulantním režimu v podmínkách gynekologické ordinace. Ceska Gynekol 2010; 75 (6): 506–512.

34. Kužel D, Hrazdírová L, Mára M et al. Management a výsledky ambulantní hysteroskopie. Ceska Gynekol 2012; 77 (4): 308–313.

35. Driák D, Sehnal B, Jarošová L et al. Perforace dělohy při nitroděložních výkonech a její řešení. Ceska Gynekol 2022; 87 (4): 295–301. doi: 10.48095/cccg2022295.

36. El-Toukhy T, Campo R, Khalaf Y et al. Hysteroscopy in recurrent in-vitro fertilisation failure (TROPHY): a multicentre, randomised controlled trial. Lancet 2016; 387 (10038): 2614–2621. doi: 10.1016/S0140-6736 (16) 00258-0.

ORCID autorů

B. Sehnal 0000-0003-2622-2181

K. Maxová 0009-0003-3473-4766

M. J. Halaška 0000-0001-6055-2569

M. Hruda 0000-0002-7606-5164

L. Rob 0000-0003-3770-651X

Doručeno/Submitted: 28. 1. 2024

Přijato/Accepted: 29. 2. 2024

MUDr. Borek Sehnal, Ph.D.

Gynekologicko-porodnická klinika

3. LF UK a FNKV

Šrobárova 1150/50