DOI QR코드

DOI QR Code

Prevalence and confounders of chronic endometritis diagnosed using CD138 in patients with recurrent implantation failure

  • Hye Jeong Hue (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Hyunji Choi (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Hyun Kyoung Lee (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Jung Ryeol Lee (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Byung Chul Jee (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Chang Woo Choo (Department of Obstetrics and Gynecology, Seoul Maria Fertility Hospital) ;
  • Seul Ki Kim (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital)
  • Received : 2023.06.01
  • Accepted : 2023.11.09
  • Published : 2024.06.30

Abstract

Objective: This retrospective study aimed to investigate the prevalence of chronic endometritis, diagnosed using CD138 immunohistochemistry, among infertile women and to assess the association between chronic endometritis and recurrent implantation failure (RIF). Methods: In total, 266 patients who underwent hysteroscopy due to infertility between 2019 and 2020 were included in the analysis. Of these, 136 patients with RIF and 130 non-RIF patients were included in the study. CD138 immunohistochemistry test results, blood biomarkers (including natural killer cells, white blood cells, and the lymphocyte-to-neutrophil ratio), and data on pregnancy outcomes were obtained. If the CD138 test yielded a positive result, the patients received antibiotic treatment. Results: The overall proportion of CD138-positive patients was 32.7% (87/266). The CD138 positivity rate was not related to the number of cycles with implantation failure. In the RIF patient group, no significant associations were found between CD138 positivity and peripheral blood markers. The clinical pregnancy rates were similar between infertile women treated with antibiotics for chronic endometritis and those without chronic endometritis. Conclusion: To improve the pregnancy rate in infertile patients, it may be helpful to combine CD138 testing with other laboratory tests and administer antibiotic treatment if the result is positive.

Keywords

Acknowledgement

All authors thank the patients and staff of the Seoul Maria Fertility Hospital for their contribution.

References

  1. El-Toukhy T, Taranissi M. Towards better quality research in recurrent implantation failure: standardizing its definition is the first step. Reprod Biomed Online 2006;12:383-5.  https://doi.org/10.1016/S1472-6483(10)61014-0
  2. Scantamburlo VM, Linsingen RV, Centa LJ, Toso KF, Scaraboto D, Araujo Junior E, et al. Association between decreased ovarian reserve and poor oocyte quality. Obstet Gynecol Sci 2021;64:532-9.  https://doi.org/10.5468/ogs.20168
  3. Liu C, Li Y, Jiang H, Liu Y, Song X. The clinical outcomes of fresh versus frozen embryos transfer in women ≥40 years with poor ovarian response. Obstet Gynecol Sci 2021;64:284-92.  https://doi.org/10.5468/ogs.20124
  4. Quaas A, Dokras A. Diagnosis and treatment of unexplained infertility. Rev Obstet Gynecol 2008;1:69-76. 
  5. Song D, Feng X, Zhang Q, Xia E, Xiao Y, Xie W, et al. Prevalence and confounders of chronic endometritis in premenopausal women with abnormal bleeding or reproductive failure. Reprod Biomed Online 2018;36:78-83.  https://doi.org/10.1016/j.rbmo.2017.09.008
  6. 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;96:1451-6.  https://doi.org/10.1016/j.fertnstert.2011.09.039
  7. McQueen DB, Perfetto CO, Hazard FK, Lathi RB. Pregnancy outcomes in women with chronic endometritis and recurrent pregnancy loss. Fertil Steril 2015;104:927-31.  https://doi.org/10.1016/j.fertnstert.2015.06.044
  8. Thum MY, Bhaskaran S, Abdalla HI, Ford B, Sumar N, Shehata H, et al. An increase in the absolute count of CD56dimCD16+CD69+ NK cells in the peripheral blood is associated with a poorer IVF treatment and pregnancy outcome. Hum Reprod 2004;19:2395-400.  https://doi.org/10.1093/humrep/deh378
  9. Neelam P, Vitthala S. Are the causes of recurrent implantation failure a myth or evidence based reality? Fertil Steril 2011;96:S279. 
  10. Romero R, Espinoza J, Mazor M. Can endometrial infection/inflammation explain implantation failure, spontaneous abortion, and preterm birth after in vitro fertilization? Fertil Steril 2004;82:799-804.  https://doi.org/10.1016/j.fertnstert.2004.05.076
  11. Bouet PE, El Hachem H, Monceau E, Gariepy 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;105:106-10.  https://doi.org/10.1016/j.fertnstert.2015.09.025
  12. 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;93:437-41.  https://doi.org/10.1016/j.fertnstert.2008.12.131
  13. 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;110:103-12.  https://doi.org/10.1016/j.fertnstert.2018.03.017
  14. 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;30:323-30.  https://doi.org/10.1093/humrep/deu292
  15. Cravello L, Porcu G, D'Ercole C, Roger V, Blanc B. Identification and treatment of endometritis. Contracept Fertil Sex 1997;25:585-6. 
  16. Adegboyega PA, Pei Y, McLarty J. Relationship between eosinophils and chronic endometritis. Hum Pathol 2010;41:33-7.  https://doi.org/10.1016/j.humpath.2009.07.008
  17. 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;289:1363-9.  https://doi.org/10.1007/s00404-013-3131-2
  18. Song D, Li TC, Zhang Y, Feng X, Xia E, Huang X, et al. Correlation between hysteroscopy findings and chronic endometritis. Fertil Steril 2019;111:772-9.  https://doi.org/10.1016/j.fertnstert.2018.12.007
  19. Kitaya K, Yasuo T. Inter-observer and intra-observer variability in immunohistochemical detection of endometrial stromal plasmacytes in chronic endometritis. Exp Ther Med 2013;5:485-8.  https://doi.org/10.3892/etm.2012.824
  20. Bayer-Garner IB, Nickell JA, Korourian S. Routine syndecan-1 immunohistochemistry aids in the diagnosis of chronic endometritis. Arch Pathol Lab Med 2004;128:1000-3.  https://doi.org/10.5858/2004-128-1000-RSIAIT
  21. Kitaya K, Tada Y, Hayashi T, Taguchi S, Funabiki M, Nakamura Y. Comprehensive endometrial immunoglobulin subclass analysis in infertile women suffering from repeated implantation failure with or without chronic endometritis. Am J Reprod Immunol 2014;72:386-91.  https://doi.org/10.1111/aji.12277
  22. 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;109:832-9.  https://doi.org/10.1016/j.fertnstert.2018.01.022
  23. Kitaya K, Yasuo T. Immunohistochemistrical and clinicopathological characterization of chronic endometritis. Am J Reprod Immunol 2011;66:410-5.  https://doi.org/10.1111/j.1600-0897.2011.01051.x
  24. Kitaya K. Prevalence of chronic endometritis in recurrent miscarriages. Fertil Steril 2011;95:1156-8.  https://doi.org/10.1016/j.fertnstert.2010.09.061
  25. McQueen DB, Maniar KP, Hutchinson A, Confino R, Bernardi L, Pavone ME. Redefining chronic endometritis: the importance of endometrial stromal changes. Fertil Steril 2021;116:855-61.  https://doi.org/10.1016/j.fertnstert.2021.04.036
  26. 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:e13369. 
  27. Mitter VR, Meier S, Rau TT, Gillon T, Mueller MD, Zwahlen M, et al. Treatment following hysteroscopy and endometrial diagnostic biopsy increases the chance for live birth in women with chronic endometritis. Am J Reprod Immunol 2021;86:e13482. 
  28. Demirdag E, Guler I, Cevher Akdulum MF, Sahin E, Erdem O, Erdem A, et al. Subsequent IVF outcomes following antibiotic therapy for chronic endometritis in patients with recurrent implantation failure. J Obstet Gynaecol Res 2021;47:4350-6.  https://doi.org/10.1111/jog.15037
  29. Fan X, Li X, Li Y, Liao J, Chen H, Li Y, et al. Endometrial CD138 count appears to be a negative prognostic indicator for patients who have experienced previous embryo transfer failure. Fertil Steril 2019;112:1103-11.  https://doi.org/10.1016/j.fertnstert.2019.08.006
  30. Zargar M, Ghafourian M, Nikbakht R, Mir Hosseini V, Moradi Choghakabodi P. Evaluating chronic endometritis in women with recurrent implantation failure and recurrent pregnancy loss by hysteroscopy and immunohistochemistry. J Minim Invasive Gynecol 2020;27:116-21.  https://doi.org/10.1016/j.jmig.2019.02.016
  31. 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:e12719. 
  32. Chen YQ, Fang RL, Luo YN, Luo CQ. Analysis of the diagnostic value of CD138 for chronic endometritis, the risk factors for the pathogenesis of chronic endometritis and the effect of chronic endometritis on pregnancy: a cohort study. BMC Womens Health 2016;16:60. 
  33. Groth JV. Chronic endometritis and the plasma cell, fact versus fiction. Fertil Steril 2018;109:788. 
  34. Kim CW, Goldberger OA, Gallo RL, Bernfield M. Members of the syndecan family of heparan sulfate proteoglycans are expressed in distinct cell-, tissue-, and development-specific patterns. Mol Biol Cell 1994;5:797-805.  https://doi.org/10.1091/mbc.5.7.797
  35. 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:e12782. 
  36. McQueen DB, Bernardi LA, Stephenson MD. Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise. Fertil Steril 2014;101:1026-30.  https://doi.org/10.1016/j.fertnstert.2013.12.031
  37. Tang AW, Alfirevic Z, Quenby S. Natural killer cells and pregnancy outcomes in women with recurrent miscarriage and infertility: a systematic review. Hum Reprod 2011;26:1971-80.  https://doi.org/10.1093/humrep/der164
  38. Li Y, Yu S, Huang C, Lian R, Chen C, Liu S, et al. Evaluation of peripheral and uterine immune status of chronic endometritis in patients with recurrent reproductive failure. Fertil Steril 2020;113:187-96.  https://doi.org/10.1016/j.fertnstert.2019.09.001
  39. Ramos-Medina R, Garcia-Segovia A, Gil J, Carbone J, Aguaron de la Cruz A, Seyfferth A, et al. Experience in IVIg therapy for selected women with recurrent reproductive failure and NK cell expansion. Am J Reprod Immunol 2014;71:458-66.  https://doi.org/10.1111/aji.12217
  40. Beer AE, Kwak JY, Ruiz JE. Immunophenotypic profiles of peripheral blood lymphocytes in women with recurrent pregnancy losses and in infertile women with multiple failed in vitro fertilization cycles. Am J Reprod Immunol 1996;35:376-82.  https://doi.org/10.1111/j.1600-0897.1996.tb00497.x
  41. Timmons BW, Cieslak T. Human natural killer cell subsets and acute exercise: a brief review. Exerc Immunol Rev 2008;14:8-23.