Immunohistochemical characteristics of the endometrium in women with recurrent pregnancy loss and chronic endometritis




recurrent miscarriage, chronic endometritis, syndecan-1, cyclin E, micronized progesterone


Objective: to study endometrium state in women with recurrent miscarriage and chronic endometritis by determining of nuclear cyclin E and syndecan-1, followed by a study of the effectiveness of proposed scheme for managing pregnancy in this category of patients.
Materials and methods. Endometrium state (in particular its immunohistochemical characteristics) was studied by determining syndecan-1 in endometrial samples during hysteroscopy or pipelle biopsy in 68 women (main group) with recurrent miscarriage, followed by an analysis of the effectiveness of the proposed schemes of pregravid preparation. The women of the main group were divided into: subgroup 1 (40 pregnant women), whose treatment regimen included antibiotic therapy, folates and micronized progesterone at the pregravid stage; subgroup 2 (28 participants), whose treatment regimen included antibacterial drugs, folate at the pregravid stage and micronized progesterone from early gestation.
The control group consisted of 30 re-pregnant women without a history of reproductive losses.
Results. Features of the endometrium state in women with recurrent miscarriage are characterized by the presence of the CD138 protein (syndecan-1) and an abnormal (elevated) level of nuclear cyclin E, which indicates a morphological reorganization of the endometrial layer and its unpreparedness for successful implantation and further gestation. This study proved successful correction of the endometrium state at the stage of preconception preparation due to the use of micronized progesterone Utrogestan®, which consisted in reducing the percentage of reproductive losses, improving the course of pregnancy and childbirth.
Conclusions. Utrogestan is a reliable, safe and effective treatment for women with recurrent miscarriage against the background of chronic endometritis even at the stage of preconception preparation. Such regimen allows transforming the endometrium and preparing it for implantation, thereby significantly improving the microenvironment for the early embryo development and successful pregnancy.

Author Biographies

S.B. Chechuha, National Pirogov Memorial Medical University, Vinnytsia

MD, professor, Obstetrics and Gynecology Department No. 2

P.M. Nevhadovska, National Pirogov Memorial Medical University, Vinnytsia

Postgraduate student, Obstetrics and Gynecology Department No. 2

O.A. Nochvina, National Pirogov Memorial Medical University, Vinnytsia

MD, associate professor, Obstetrics and Gynecology Department No. 2


  1. Practice Committee of the American Society for Reproductive Medicine. “Definitions of infertility and recurrent pregnancy loss: a committee opinion.” Fertil Steril 113.3 (2020): 533–5.
  2. ESHRE Early Pregnancy Guideline Development Group. Guideline on the Management of Recurrent Pregnancy Loss. Version 2. ESHRE Grimbergen, Belgium (2017).
  3. Royal College of Obstetricians and Gynaecologists. The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. RCOG: London, UK (2011).
  4. Toth, B., Würfel, W., Bohlmann, M., et al. “Recurrent Miscarriage: Diagnostic and Therapeutic Procedures. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/050).” Geburtshilfe und Frauenheilkunde 78.4 (2018): 364–81. DOI: 10.1055/a-0586-4568
  5. Ministry of Health of Ukraine. Order from 03.11.2008 № 624 “On approval of clinical protocols for obstetric and gynecological care”.
  6. El Hachem, H., Crepaux, V., May-Panloup, P., et al. “Recurrent pregnancy loss: current perspectives.” Int J Women’s Health 9 (2017): 331–45. DOI: 10.2147/IJWH.S100817
  7. Hennessy, M., Dennehy, R., Meaney, S., et al. “Clinical practice guidelines for recurrent miscarriage in high-income countries: a systematic review.” Reprod Biomed Online 42.6 (2021): 1146–71. DOI: 10.1016/j.rbmo.2021.02.014
  8. Jeve, Y.B., Davies, W. “Evidence-based management of recurrent miscarriages.” J Hum Reprod Sci 7.3 (2014): 159–69. DOI: 10.4103/0974-1208.142475
  9. Chechuga, S.B., Nochvina, E.A., Sali, G.A. “Pathogenetic therapy of miscarriage in women with hyperhomocysteinemia and progestogen deficiency.” Health of Woman 5 (2012): 80–5.
  10. Pirtea, P., Cicinelli, E., De Nola, R., et al. “Endometrial causes of recurrent pregnancy losses: endometriosis, adenomyosis, and chronic endometritis.” Fertil Steril 115.3 (2021): 546–60. DOI: 10.1016/j.fertnstert.2020.12.010
  11. Daher, S., Mattar, R., Gueuvoghlanian-Silva, B., Torloni, M. “Genetic polymorphisms and recurrent spontaneous abortions: an over view of current knowledge.” Am J Reprod Immunol 67.4 (2012): 341–7.
  12. Johnston-MacAnanny, E.B., Hartnett, J., Engmann, L.L., et al. “Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization.” Fertil Steril 93.2 (2010): 437–41. DOI: 10.1016/j.fertnstert.2008.12.131
  13. Ticconi, C., Pietropolli, A., Di Simone, N., et al. “Endometrial Immune Dysfunction in Recurrent Pregnancy Loss.” Int J Mol Sci 20.21 (2019): 5332. DOI: 10.3390/ijms20215332
  14. De Carolis, C., Perricone, C., Perricone, R. “War and peace at the feto-placental front line: recurrent spontaneous abortion.” IMAJ 16 (2014): 667–8.
  15. Veropotvelyan, N.P. “Reviewing efficacy of progestogens in recurrent early reproductive losses.” Reproductive endocrinology 31 (2016): 22–33. DOI: 10.18370/2309-4117.2016.31.22-33
  16. Berghella, V. Early pregnancy loss: Obstetric evidence based guidelines. 2nd edition. New York. CRC (2012): 142–149.
  17. Zhuk, S.I., Chechuga, S.B., Nochvina, O.A. “Micronized progesteron in complex pregravid preparation and pregnancy management in women with recurrent pregnancy loss on the background of chronic endometritis.” Reproductive endocrynology 54 (2020): 72–8. DOI: 10.18370/2309-4117.2020.54.72-78
  18. Bayer-Garner, I.B., Nickell, J.A., Korourian, S. “Routine syndecan-1 immunohistochemistry aids in the diagnosis of chronic endometritis.” Arch Pathol Lab Med 128.9 (2004): 1000–3.
  19. Palaiologou, M., Delladetsima, I., Tiniakos, D. “CD138 (syndecan-1) expression in health and disease.” Histol Histopathol 29.2 (2014): 177–89. DOI: 10.14670/HH-29.177
  20. 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 27.1 (2020): 116–21. DOI: 10.1016/j.jmig.2019.02.016
  21. Sahasrabudhe, N., Mobasseri, M., Reznik, S.E., Williams, Z. “Chronic Endometritis and Recurrent Pregnancy Loss.” Curr Obstet Gynecol Rep 6 (2017): 55–61.
  22. Kitaya, K., Yasuo, T. “Inter-observer and intra-observer variability in immunohistochemical detection of endometrial stromal plasmacytes in chronic endometritis.” Exp Ther Med 5.2 (2013): 485–8.
  23. Kind, S., Merenkow, C., Büscheck, F., et al. “Prevalence of Syndecan-1 (CD138) Expression in Different Kinds of Human Tumors and Normal Tissues.” Disease Markers 2019 (2019): 4928315. DOI: 10.1155/2019/4928315
  24. Dubowy, R.L., Feinberg, R.F., Keefe, D.L., et al.“Improved endometrial assessment using cyclin E and p27.” Fertil Steril 80.1 (2003): 146–56. DOI: 10.1016/s0015-0282(03)00573-9
  25. Stephenson, M.D., Willis, M.Y., Schultz, P., et al. “Abnormal nuclear cyclin E expression in endometrial glands of patients with recurrent pregnancy loss (RPL): response to vaginal micronized progesterone adminstration.” Fertil Steril 92.3 (2009): S244–S245.
  26. Stephenson, M.D., McQueen, D., Winter, M., Kliman, H.J. “Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss.” Fertil Steril 107 (2017): 684–90.
  27. Coomarasamy, A., Williams, H., Truchanowicz, E., et al. “A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.” N Engl J Med 373.22 (2015): 2141–8. DOI: 10.1056/NEJMoa1504927
  28. Coomarasamy, A., Devall, A.J., Cheed, V., et al. “A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy.” N Engl J Med 380.19 (2019): 1815–24. DOI: 10.1056/NEJMoa1813730
  29. Zhuk, S.I., Kondratiuk, V.K., Dziuba, G.A. Ethical code of a doctor who prescribes gestagens in obstetricand gynecological practice. Evidence base. Methodical recommendations. P.L. Shupik NMAPE; Department of Obstetrics, Gynecology and Fetal Medicine. Kyiv (2019): 23 p.
  30. Coomarasamy, A., Dhillon-Smith, R.K., Papadopoulou, A., et al. “Recurrent miscarriage: evidence to accelerate action.” Lancet 397.10285 (2021): 1675–82. DOI: 10.1016/S0140-6736(21)00681-4
  31. Devall, A.J., Papadopoulou, A., Podesek, M., et al. “Progestogens for preventing miscarriage: a network meta-analysis.” Cochrane Database of Systematic Reviews 4 (2021): CD013792. DOI: 10.1002/14651858.CD013792
  32. Romero, R., Conde-Agudelo, A., El-Refaie, W., et al. “Vaginal progesterone decreases preterm birth and neonatal morbidity and mortality in women with a twin gestation and a short cervix: an updated meta-analysis of individual patient data.” Ultrasound Obstet Gynecol 49 (2017): 303–14. DOI: 10.1002/uog.17397
  33. EPPPIC Group. “Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials.” Lancet 397.10280 (2021): 1183–94. DOI: 10.1016/S0140-6736(21)00217-8
  34. Care, A., Nevitt, S.J., Medley, N., et al. “Interventions to prevent spontaneous preterm birth in women with singleton pregnancy who are at high risk: systematic review and network meta-analysis.” BMJ 376 (2022): e064547.
  35. Nevhadovska, P.M., Chechuga, S.B., Nochvina, Е.A., Dzis, N.P. “Clinical characteristics of women with recurrent pregnancy loss and chronic endometritis.” Reports of Vinnytsia National Medical University 24.4 (2020): 629–33. DOI: 10.31393/reports-vnmedical-2020-24(4)-12



How to Cite

Chechuha, S., Nevhadovska, P., & Nochvina, O. (2022). Immunohistochemical characteristics of the endometrium in women with recurrent pregnancy loss and chronic endometritis. REPRODUCTIVE ENDOCRINOLOGY, (65), 60–66.



Pregnancy and childbirth