Vpliv zdravljenja kroničnega endometritisa na uspešnost postopkov zunajtelesne oploditve – sistematični pregled literature

Chronic endometritis (CE) is accompanied by mild symptoms only and is thought to be associated with infertility, recurrent miscarriages, and recurrent implantation failure (RIF) in assisted reproductive technology (ART) procedures. The role of identification and treatment of CE in patients in ART is still controversial, and the aim of this systematic review was to analyse the studies to determine the impact of CE treatment on reproductive outcomes in infertile women undergoing ART procedures.

A systematic literature review of the Medline collection was conducted. We used descriptors from the Medical subject headings (Mesh) thesaurus, which included the keywords chronic endometritis AND treatment AND pregnancy. We have included articles issued from January 1971 until March 2022.

Eight studies with different treatment regimens were included in this review. Most studies have found statistically significant differences in reproductive outcomes after CE treatment.

CE treatment may have a positive effect on outcomes in subsequent ART procedures, but larger randomized studies are needed. Downloads

1. Greenwood SM, Moran JJ. Chronic endometritis: morphologic and clinical observations. Obstet Gynecol. 1981;58(2):176-84. PMID: 7254729 2. McQueen DB, Maniar KP, Hutchinson A, Confino R, Bernardi L, Pavone ME. Redefining chronic endometritis: the importance of endometrial stromal changes. Fertil Steril. 2021;116(3):855-61. DOI: 10.1016/j.fertnstert.2021.04.036 PMID: 34120737 3. Zhang Y, Xu H, Liu Y, Zheng S, Zhao W, Wu D, 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 PMID: 31373128 4. Coughlan C, Ledger W, Wang Q, Liu F, Demirol A, Gurgan T, et al. Recurrent implantation failure: definition and management. Reprod Biomed Online. 2014;28(1):14-38. DOI: 10.1016/j.rbmo.2013.08.011 PMID: 24269084 5. Valdes CT, Schutt A, Simon C. Implantation failure of endometrial origin: it is not pathology, but our failure to synchronize the developing embryo with a receptive endometrium. Fertil Steril. 2017;108(1):15-8. DOI: 10.1016/j.fertnstert.2017.05.033 PMID: 28668151 6. Buzzaccarini G, Vitagliano A, Andrisani A, Santarsiero CM, Cicinelli R, Nardelli C, et al. Chronic endometritis and altered embryo implantation: a unified pathophysiological theory from a literature systematic review. J Assist Reprod Genet. 2020;37(12):2897-911. DOI: 10.1007/s10815-020-01955-8 PMID: 33025403 7. Wang WJ, Zhang H, Chen ZQ, Zhang W, Liu XM, Fang JY, et al. Endometrial TGF-β, IL-10, IL-17 and autophagy are dysregulated in women with recurrent implantation failure with chronic endometritis. Reprod Biol Endocrinol. 2019;17(1):2. DOI: 10.1186/s12958-018-0444-9 PMID: 30606202 8. Kitaya K, Yasuo T. Aberrant expression of selectin E, CXCL1, and CXCL13 in chronic endometritis. Mod Pathol. 2010;23(8):1136-46. DOI: 10.1038/modpathol.2010.98 PMID: 20495539 9. Wu D, Kimura F, Zheng L, Ishida M, Niwa Y, Hirata K, et al. Chronic endometritis modifies decidualization in human endometrial stromal cells. Reprod Biol Endocrinol. 2017;15(1):16. DOI: 10.1186/s12958-017-0233-x PMID: 28259137 10. Matteo M, Cicinelli E, Greco P, Massenzio F, Baldini D, Falagario T, et al. Abnormal pattern of lymphocyte subpopulations in the endometrium of infertile women with chronic endometritis. Am J Reprod Immunol. 2009;61(5):322-9. DOI: 10.1111/j.1600-0897.2009.00698.x PMID: 19341383 11. Carvalho FM, Aguiar FN, Tomioka R, de Oliveira RM, Frantz N, Ueno J. 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):152-6. DOI: 10.1016/j.ejogrb.2013.05.012 PMID: 23773528 12. Pinto V, Matteo M, Tinelli R, Mitola PC, De Ziegler D, Cicinelli E. Altered uterine contractility in women with chronic endometritis. Fertil Steril. 2015;103(4):1049-52. DOI: 10.1016/j.fertnstert.2015.01.007 PMID: 25681852 13. Moreno I, Cicinelli E, Garcia-Grau I, Gonzalez-Monfort M, Bau D, Vilella F, 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.e1-16. DOI: 10.1016/j.ajog.2018.02.012 PMID: 29477653 14. Haggerty CL, Peipert JF, Weitzen S, Hendrix SL, Holley RL, Nelson DB, et al.; PID Evaluation and Clinical Health (PEACH) Study Investigators. Predictors of chronic pelvic pain in an urban population of women with symptoms and signs of pelvic inflammatory disease. Sex Transm Dis. 2005;32(5):293-9. DOI: 10.1097/01.olq.0000162361.69041.a5 PMID: 15849530 15. Cicinelli E, De Ziegler D, Nicoletti R, Colafiglio G, Saliani N, Resta L, et al. Chronic endometritis: correlation among hysteroscopic, histologic, and bacteriologic findings in a prospective trial with 2190 consecutive office hysteroscopies. Fertil Steril. 2008;89(3):677-84. DOI: 10.1016/j.fertnstert.2007.03.074 PMID: 17531993 16. Johnstone FD, Williams AR, Bird GA, Bjornsson S. Immunohistochemical characterization of endometrial lymphoid cell populations in women infected with human immunodeficiency virus. Obstet Gynecol. 1994;83(4):586-93. DOI: 10.1097/00006250-199404000-00017 PMID: 7907778 17. Frank TS, Himebaugh KS, Wilson MD. Granulomatous endometritis associated with histologically occult cytomegalovirus in a healthy patient. Am J Surg Pathol. 1992;16(7):716-20. DOI: 10.1097/00000478-199207000-00010 PMID: 1326899 18. Cicinelli E, Matteo M, Tinelli R, Lepera A, Alfonso R, Indraccolo U, et al. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod. 2015;30(2):323-30. DOI: 10.1093/humrep/deu292 PMID: 25385744 19. 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. DOI: 10.1016/j.fertnstert.2018.03.017 PMID: 29908776 20. Kitaya K, Matsubayashi H, Takaya Y, Nishiyama R, Yamaguchi K, Takeuchi T, 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(5):78. DOI: 10.1111/aji.12719 PMID: 28608596 21. Cicinelli E, Matteo M, Trojano G, Mitola PC, Tinelli R, Vitagliano A, et al. Chronic endometritis in patients with unexplained infertility: prevalence and effects of antibiotic treatment on spontaneous conception. Am J Reprod Immunol. 2018;79(1):e12782. DOI: 10.1111/aji.12782 PMID: 29135053 22. Bouet PE, El Hachem H, Monceau E, Gariépy G, Kadoch IJ, Sylvestre C. 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 PMID: 26456229 23. Liu Y, Chen X, Huang J, Wang CC, Yu MY, Laird S, 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(5):832-9. DOI: 10.1016/j.fertnstert.2018.01.022 PMID: 29778382 24. Haggerty CL, Ness RB, Amortegui A, Hendrix SL, Hillier SL, Holley RL, et al. Endometritis does not predict reproductive morbidity after pelvic inflammatory disease. Am J Obstet Gynecol. 2003;188(1):141-8. DOI: 10.1067/mob.2003.87 PMID: 12548208 25. Bayer-Garner IB, Nickell JA, Korourian S. Routine syndecan-1 immunohistochemistry aids in the diagnosis of chronic endometritis. Arch Pathol Lab Med. 2004;128(9):1000-3. DOI: 10.5858/2004-128-1000-RSIAIT PMID: 15335255 26. Kitaya K, Yasuo T. Inter-observer and intra-observer variability in immunohistochemical detection of endometrial stromal plasmacytes in chronic endometritis. Exp Ther Med. 2013;5(2):485-8. DOI: 10.3892/etm.2012.824 PMID: 23407614 27. Liu Y, Chen X, Huang J, Wang CC, Yu MY, Laird S, 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(5):832-9. DOI: 10.1016/j.fertnstert.2018.01.022 PMID: 29778382 28. Cicinelli E, Vitagliano A, Kumar A, Lasmar RB, Bettocchi S, Haimovich S, et al.; 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. DOI: 10.1016/j.fertnstert.2019.03.004 PMID: 31104760 29. Yang R, Du X, Wang Y, Song X, Yang Y, Qiao J. The hysteroscopy and histological diagnosis and treatment value of chronic endometritis in recurrent implantation failure patients. Arch Gynecol Obstet. 2014;289(6):1363-9. DOI: 10.1007/s00404-013-3131-2 PMID: 24395012 30. Song D, Li TC, Zhang Y, Feng X, Xia E, Huang X, et al. Correlation between hysteroscopy findings and chronic endometritis. Fertil Steril. 2019;111(4):772-9. DOI: 10.1016/j.fertnstert.2018.12.007 PMID: 30683588 31. Johnston-MacAnanny EB, Hartnett J, Engmann LL, Nulsen JC, Sanders MM, Benadiva CA. Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. Fertil Steril. 2010;93(2):437-41. DOI: 10.1016/j.fertnstert.2008.12.131 PMID: 19217098 32. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372(71):n71. DOI: 10.1136/bmj.n71 PMID: 33782057 33. Kasius JC, Fatemi HM, Bourgain C, Sie-Go DM, Eijkemans RJ, Fauser BC, et al. The impact of chronic endometritis on reproductive outcome. Fertil Steril. 2011;96(6):1451-6. DOI: 10.1016/j.fertnstert.2011.09.039 PMID: 22019126 34. Robertson SA, Jin M, Yu D, Moldenhauer LM, Davies MJ, Hull ML, et al. Corticosteroid therapy in assisted reproduction - immune suppression is a faulty premise. Hum Reprod. 2016;31(10):2164-73. DOI: 10.1093/humrep/dew186 PMID: 27591233 35. Zhang T, Huang C, Du Y, Lian R, Mo M, Zeng Y, et al. Successful treatment with intrauterine delivery of dexamethasone for repeated implantation failure. Am J Reprod Immunol. 2017;78(6):e12766. DOI: 10.1111/aji.12766 PMID: 28921750 36. Xiong Y, Chen Q, Chen C, Tan J, Wang Z, Gu F, et al. 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):413-21. DOI: 10.1016/j.fertnstert.2021.03.036 PMID: 33926717 37. Sekulovski N, Whorton AE, Shi M, MacLean JA, Hayashi K. Endometriotic inflammatory microenvironment induced by macrophages can be targeted by niclosamide†. In Vivo. 2019;100(2):398-408. DOI: 10.1093/biolre/ioy222 PMID: 30329025 38. Sfakianoudis K, Simopoulou M, Nitsos N, Lazaros L, Rapani A, Pantou A, 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 PMID: 30804135 39. Canumalla SA, Blakemore JK, Grifo JA, Keefe DL. What is the most effective treatment for endometritis in women undergoing assisted reproductive technology? Fertil Steril. 2019;105(3):106-10. DOI: 10.1016/j.fertnstert.2019.07.961 40. Crum CP, Egawa K, Fenoglio CM, Richart RM. Chronic endometritis: the role of immunohistochemistry in the detection of plasma cells. Am J Obstet Gynecol. 1983;147(7):812-5. DOI: 10.1016/0002-9378(83)90045-5 PMID: 6359886 41. Gilmore H, Fleischhacker D, Hecht JL. Diagnosis of chronic endometritis in biopsies with stromal breakdown. Hum Pathol. 2007;38(4):581-4. DOI: 10.1016/j.humpath.2006.09.002 PMID: 17188330 42. Adegboyega PA, Pei Y, McLarty J. Relationship between eosinophils and chronic endometritis. Hum Pathol. 2010;41(1):33-7. DOI: 10.1016/j.humpath.2009.07.008 PMID: 19801162 43. Li Y, Xu S, Yu S, Huang C, Lin S, Chen W, et al. Diagnosis of chronic endometritis: how many CD138+ cells/HPF in endometrial stroma affect pregnancy outcome of infertile women? Am J Reprod Immunol. 2021;85(5):e13369. DOI: 10.1111/aji.13369 PMID: 33152123 44. Liu Y, Chen X, Huang J, Wang CC, Yu MY, Laird S, 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(5):832-9. DOI: 10.1016/j.fertnstert.2018.01.022 PMID: 29778382 45. Tersoglio AE, Salatino DR, Reinchisi G, Gonzalez A, Tersoglio S, Marlia C. Repeated implantation failure in oocyte donation. What to do to improve the endometrial receptivity? JBRA Assist Reprod. 2015;19(2):44-52. DOI: 10.5935/1518-0557.20150012 PMID: 27206087 46. Huang W, Liu B, He Y, Xie Y, Liang T, Bi Y, et al. Variation of diagnostic criteria in women with chronic endometritis and its effect on reproductive outcomes: A systematic review and meta-analysis. J Reprod Immunol. 2020;140:103146. DOI: 10.1016/j.jri.2020.103146 PMID: 32442825 47. Moreno I, Codoñer FM, Vilella F, Valbuena D, Martinez-Blanch JF, Jimenez-Almazán J, et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016;215(6):684-703. DOI: 10.1016/j.ajog.2016.09.075 PMID: 27717732 48. Verstraelen H, Vilchez-Vargas R, Desimpel F, Jauregui R, Vankeirsbilck N, Weyers S, et al. Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1-2 region of the 16S rRNA gene. PeerJ. 2016;4:e1602. DOI: 10.7717/peerj.1602 PMID: 26823997 49. Benner M, Ferwerda G, Joosten I, van der Molen RG. How uterine microbiota might be responsible for a receptive, fertile endometrium. Hum Reprod Update. 2018;24(4):393-415. DOI: 10.1093/humupd/dmy012 PMID: 29668899 50. Cicinelli E, Ballini A, Marinaccio M, Poliseno A, Coscia MF, Monno R, et al. Microbiological findings in endometrial specimen: our experience. Arch Gynecol Obstet. 2012;285(5):1325-9. DOI: 10.1007/s00404-011-2138-9 PMID: 22113463 51. Haahr T, Zacho J, Bräuner M, Shathmigha K, Skov Jensen J, Humaidan P. Reproductive outcome of patients undergoing in vitro fertilisation treatment and diagnosed with bacterial vaginosis or abnormal vaginal microbiota: a systematic PRISMA review and meta-analysis. BJOG. 2019;126(2):200-7. DOI: 10.1111/1471-0528.15178 PMID: 29469992 52. Cicinelli E, De Ziegler D, Nicoletti R, Tinelli R, Saliani N, Resta L, et al. Poor reliability of vaginal and endocervical cultures for evaluating microbiology of endometrial cavity in women with chronic endometritis. Gynecol Obstet Invest. 2009;68(2):108-15. DOI: 10.1159/000223819 PMID: 19521097 53. Moreno I, Codoñer FM, Vilella F, Valbuena D, Martinez-Blanch JF, Jimenez-Almazán J, et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016;215(6):684-703. DOI: 10.1016/j.ajog.2016.09.075 PMID: 27717732 54. Liu Y, Ko EY, Wong KK, Chen X, Cheung WC, Law TS, et al. Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-based method. Fertil Steril. 2019;112(4):707-717.e1. DOI: 10.1016/j.fertnstert.2019.05.015 PMID: 31327470 55. Kushnir VA, Solouki S, Sarig-Meth T, Vega MG, Albertini DF, Darmon SK, et al. Systemic Inflammation and Autoimmunity in Women with Chronic Endometritis. Am J Reprod Immunol. 2016;75(6):672-7. DOI: 10.1111/aji.12508 PMID: 26952510 56. 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. Przegl Menopauz. 2020;19(2):90-100. 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