The first experience of reproductive function restoration in patients with Asherman’s syndrome using autologous mesenchymal stem cells

Clinical case




Asherman’s syndrome, hysteroscopy, autologous endometrial stem cells, prevention of intrauterine synechiae, restoration of menstruation, fertility restoration


The main goal of Asherman’s syndrome treatment is to restore the volume and shape of the uterine cavity, regenerate the endometrium and reproductive function. Recently, in addition to ultrasound diagnostics of intrauterine synechiae, office hysteroscopy is widely used. The most standardized stages of Asherman’s syndrome treatment are hysteroscopic dissection of the uterine cavity synechiae and endometrium re-adhesion prevention in the postoperative period, which is achieved by the introduction of the intrauterine device, anti-adhesive drugs or balloon catheters inserted intrauterinely.
The main difficulties are to find effective ways to prevent adhesion that occurs after removal of mechanical means from the uterine cavity and ways to restore the endometrium morphology in patients wishing to achieve pregnancy. The most promising technique in this area is the use of autologous endometrial stem cells.
Here is a case of treatment of a reproductive age patient with infertility and Asherman’s syndrome. The clinical case was a part of a clinical trial Clinical Identifier: NCT04675970. On the eve of the operative stage for uterine cavity synechiae separation 20.0 ml of venous blood was taken. Mesenchymal stem cells (MSCs) were isolated from the patient’s peripheral blood using the magnetic separation method of the autoMACS Pro Separator (Miltenyi Biotec). According to the international instructions, 6th passage MSCs were clinically used. Confirmation of belonging the derived cells to the MSCs group was performed using the set Bio-Techne FMC-020 (Great Britain). In addition, MSCs were differentiated to endometrial cells, which was confirmed using endometrial cell matching markers in generations P0-P3 (passage 0 – passage 3) with the MicroBead Kit (USA).
The operative stage of treatment included office hysteroscopy, mechanical synechiolysis in the endocervix and endometrium and introduction of a silver-containing intrauterine device. Subendometrial injection of autologous endometrial MSCs was performed to restore the endometrium structure at the end of hysteroscopy. High dose adjuvant estrogen therapy followed for 3 weeks. Pregnancy was achieved spontaneously 2 years after the intervention. The patient gave birth to a full-term baby girl.
The results of the clinical case indicate the prospects for the use of autologous blood stem cells converted into endometrial cells in the treatment of infertility in patients with CA in the absence of effect from previous attempts to restore fertility by traditional therapies.

Author Biographies

M.I. Kozub, Kharkiv Medical Academy of Postgraduate Education, Kharkiv

MD, professor, chief of the Obstetrics and Gynecology Department No. 2

S.M. Gramatiuk, Louisiana State University; Ukrainian Association of Biobanks; Institute of Cellular Biorehabilitation, Kharkiv

PhD, professor, Department of Comparative Biomedical Sciences, Louisiana State University;
President of the Ukrainian Association of Biobanks;
Director of the Institute of Cellular Biorehabilitation

M.M. Kozub, Kharkiv Medical Academy of Postgraduate Education, Kharkiv

MD, associate professor, Obstetrics and Gynecology and Oncogynecology Department

M.P. Sokol, Kharkiv Medical Academy of Postgraduate Education, Kharkiv

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

L.I. Hyrman, Kharkiv Medical Academy of Postgraduate Education, Kharkiv

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

O.V. Knihavko, Kharkiv National Medical University, Kharkiv

MD, professor, A.G. Podreza Department of Urology, Nephrology and Andrology

L.M. Savelieva, Municipal Non-Profit Enterprise of the Kharkiv Regional Council “Regional Clinical Perinatal Center”, Kharkiv



  1. Voronkova, N.M. “Treatment of chronic endometritis at the stage of pre-pregnancy training.” Clinical endocrinology and endocrine surgery 4.64 (2018): 81.
  2. Hyrman, L.I., Kozub, M.M., Sokol, M.P. Possibilities of ultrasound diagnostics in obstetrics and gynecology: A textbook for independent work of obstetricians and gynecologists. Kharkiv. KhMAPO (2017): 51 p.
  3. Kyshakevych, I.T., Kotsabyn, N.V., Radchenko, V.V. “Endometrium in the focus of gynecologist: the role of hysteroscopy and immunohistochemistry in the diagnosis of chronic endometritis, the choice of treatment.” Reproductive Endocrinology 2 (2017): 24–7.
  4. Klyucharov, I.V., Hasanov, A.A. “Surgical microhysteroscopy for intrauterine synechiae.” Practical Medicine. Actual problems of medicine 1 (2012): 94–5.
  5. Kozub, M.I., Ryzhenko, O.V. “Optimization of methods of treatment and rehabilitation of patients with infertility caused by inflammatory diseases of the uterine appendages.” Ukr J Med Biol Sport 3.1.10 (2018): С. 183–9.
  6. Kozub, M.I., Kozub, M.M., Ladna, I.D. Method of restoring endometrial receptors in patients with inflammatory diseases of the uterus. Patent of Ukraine for utility model № 109874 dated 12.09.2016. Bulletin № 17.
  7. Lysytsia, V. “Management of patients with inflammatory diseases of the pelvic organs. Review of the British Association for Sexual Health and HIV recommendations.” Medical aspects of women’s health 3 (2018): 17–23.
  8. Onlas, A.R., Dzhakupov, D.V., Barmasheva, Z.E. “Evidence-based medicine perspective on the problem of ectopic blueness.” Bulletin of KazNMU 3 (2016): 265–75.
  9. Snopkova, L.V., Cherepova, V.I., Kandyba, L.I., Sykal, I.M. “Modern possibilities of diagnosis of chronic endometritis.” Problems of uninterrupted medical training and science 3.35 (2019): 68–72.
  10. Snopkova, L.V., Kandyba, L.I., Sykal, I.M., Olhovska, V.M. “Modern features of treatment of chronic endometritis in women of reproductive age.” Problems of uninterrupted medical training and science 3.39 (2020): 55–9.
  11. Cil, N., Yaka, M., Unal, M.S., et al. “Adipose derived mesenchymal stem cell treatment in experimental Asherman syndrome induced rats.” Mol Biol Rep 47.6 (2020): 4541–52. DOI: 10.1007/s11033-020-05505-4
  12. Coccia, M.E., Becattini, C., Bracco, G.L., et al. “Intraoperative ultrasound guidance for operative hysteroscopy. A prospective study.”J Reprod Med 45 (2000): 413–8.
  13. Conforti, A., Alviggi, C., Mollo, A., et al. “The management of Asherman syndrome are view of Iiterature.” Reprod Biol Endocrinol 11.118 (2013). DOI: 10.1186/1477-7827-11-118
  14. Deans, R., Abbott, J. “Review of intrauterine adhesions.” J Minim Invasive Gynecol 17 (2010): 555–69.
  15. Di Spiezio Sardo, A., Spinelli, M., Bramante, S., et al. “Efficacy of a polyethyleneoxide-sodiumcarboxymethylcellulose gel in prevention of intrauterine adhesions after hysteroscopic surgery.” J Minim Invasive Gynecol 18.4 (2011): 462–9.
  16. Domnina, A., Novikova, P., Obidina, J., et al. “Human mesenchymal stemcells in sphereoids improve fertility in model animals with damaged endometrium.” Stem Cell Res Ther 9.1 (2018): 50. DOI: 10.1186/s13287-018-0801-9
  17. Hou, X., Liu, Y., Streuli, I., et al. “Endometrial Regeneration in Asherman’s Syndrome: Clinical and Translational evidence of Stem Cell Therapies.” Curr Stem Cell Res Ther 14.6 (2019): 454–9. DOI: 10.2174/1574888X14666190213100528
  18. Kilic, S., Yuksel, B., Pinarli, F., et al. “Effect of stemcell application on Asherman syndrome, an experimental rat model.” J Assist Reprod Genet 31 (2014): 975–82. DOI: 10.1007/s10815-014-0268-2
  19. Kitaya, K., Takeuchi, T., Mizuta, S. “Endometritis: new time, new concepts.” Fertil Steril 110.3 (2018): 344–50. DOI: 10.1016/j.fertnstert.2018.04.012
  20. Kozub, M.I., Skybina, K.P., Musatova, I.B. “Comparison of therapeutic effects of different methods of administration of mezenchimal stem cells to mice with premature ovarian insufficiency.” Problems of Endocrine Pathology 76.2 (2021): 35–40.
  21. Lee, W.-L., et al. “Focus on the Primary Prevention of Intrauterine Adhesions: Current Concept and Vision.” Int J Mol Sci 22.10 (2021): 5175. DOI: 10.3390/ijms22105175
  22. Liu, F., Hu, S., Yang, H., et al. “Hyaluronic Acid Hydrogel integrated with Mesenchymal Stem Cell-Secretome to Treat Endometrial Injury in a rat model of Asherman’s syndrome.” Adv Healthc Mater 8.14 (2019): e1900411. DOI: 10.1002/adhm.201900411
  23. Park, H.I., Kim, Y.S., Yoon, T.K., Lee, W.S. “Cronic endometritis and fertility.” Clin Exp Reprod Med 45.4 (2016): 185–192.
  24. Queckbörner, S., et al. “Endometrial stromal cells exhibit a distinct phenotypic and immunomodulatory profile.” Stem Cell Res Ther 11.1 (2020): 15. DOI: 10.1186/s13287-019-1496-2
  25. Roy, K.K., Baruah, J., Sharma, J.B., et al. “Reproductive outcome following hysteroscopic adhesiolysis in patients within fertility due to Asherman’s syndrome.” Arch Gynecol Obstet 281 (2010): 355–61.
  26. Tao, Z., Duan, H. “Expression of adhesion-related cytokines in the uterine fluid after transcervical resection of adhesion.” Zhonghua Fu Chan Ke Za Zhi 47 (2012): 734–7.
  27. Tersoglio, A.E., Tersoglio, S., Salatino, D.R., et al. “Regenerative therapy by endometrial mesenchymal stem cells in thin endometrium repeated implantation failure. A novel strategy.” JBRA Assist Reprod 24.2 (2020): 118–27. DOI: 10.5935/1518-0557.20190061
  28. Vesce, F., Jorizzo, G., Bianciotto, A., Gotti, G. “Use of intrauterine device in the management of secondary amenorrhea.” Fertil Steril 73 (2000): 162–5.
  29. Yu, D., Wong, Y.M., Cheong, Y., et al. “Asherman syndrome – one century later.” Fertil Steril 89 (2008): 759–79.
  30. Zhao, Y., Luo, Q., Zhang, X., et al. “Clinical Efficacy and Safety of Stem Cell-Based Therapy in Treating Asherman Syndrome: A System Review and Meta-Analysis.” Stem Cells Int 2020 (2020): 8820538. DOI: 10.1155/2020/8820538
  31. Zikopoulos, K.A., Kolibianakis, E.M., Platteau, P., et al. “Live delivery rates in subfertile women with Asherman’s syndrome after hysteroscopic adhesiolysis using the resectoscope or the Versapoint system.” Reprod Biomed Online 8 (2004): 720–5.



How to Cite

Kozub, M. ., Gramatiuk, S., Kozub, M., Sokol, M., Hyrman, L., Knihavko, O., & Savelieva, L. (2022). The first experience of reproductive function restoration in patients with Asherman’s syndrome using autologous mesenchymal stem cells: Clinical case. REPRODUCTIVE ENDOCRINOLOGY, (63-64), 59–66.



Treatment of infertility and pregnancy