Cell-based therapy in thin endometrium syndrome

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Of the known causes of uterine factor infertility, Asherman’s syndrome or the so-called intrauterine synechia, chronic endometritis and endometrial hypoplastic processes are most often distinguished. Thin endometrial syndrome is characterized by a decrease in the thickness of the endometrium to 7 mm or less in the proliferative phase of the menstrual cycle and a multiple decrease in the frequency of embryo implantation.

Numerous treatment strategies have so far been proposed for treating refractory thin endometrium syndrome. Recently, cell therapy has been proposed as an ideal alternative for endometrium regeneration, including the employment of stem cells, platelet-rich plasma, and growth factors as therapeutic agents. Single center, prospective, open-label study of efficacy of cell-based therapy in the complex treatment of thin endometrium syndrome in patients with infertility was conducted. The study involved 36 women aged 28 to 36 years, the middle age was 34.2 ± 1.1 years. All patients included in the study received 3 cycles of intrauterine administration of a suspension of autologous stem cells isolated from bone marrow. Bone marrow was successfully aspirated from the iliac crest in all patients. Mononuclear cells was isolated by density gradient centrifugation according to the standard method. The cell material was cryopreservated and thawed immediately before administration. The procedure for intrauterine transplantation of isolated but not cultured cells was performed on the 5th–7th day of the menstrual cycle. There were no significant adverse events related to harvest or administration. The thickness of the endometrium before and after treatment was 2.39 ± 0.64 and 6.56 ± 0.94 mm (t = –21.94, p = 0.0001), respectively. The rate of patients with an endometrial thickness of more than 7 mm after treatment was 77.8%. The effectiveness of assisted reproductive technology in patients with normal endometrial (n = 28) was 32.1%. Immunohistochemistry confirms the presence of chronic endometritis before and after treatment in 22 (61.1%) and 19 (52.8%) patients, respectively, while after treatment a significant decrease in the levels inflammatory markers was found.

作者简介

Natalya Tapil’skaya

Ott Research institute of obstetrics, gynecology and reproductology

编辑信件的主要联系方式.
Email: tapnatalia@yandex.ru
ORCID iD: 0000-0001-5309-0087
SPIN 代码: 3605-0413
Scopus 作者 ID: 167924

M.D., D.Sc. (Medicine), Professor, the Head of Reproductology Department

俄罗斯联邦, Saint Petersburg

Kseniya Ob’edkova

Ott Research institute of obstetrics, gynecology and reproductology

Email: obedkova_ks@mail.ru
ORCID iD: 0000-0002-2056-7907
SPIN 代码: 2709-2890
Scopus 作者 ID: 1048781

M.D., Ph.D. (Medicine), research scientist of Reproductology Department

俄罗斯联邦, Saint Petersburg

Alexander Gzgzyan

Ott Research institute of obstetrics, gynecology and reproductology

Email: iagmail@ott.ru
ORCID iD: 0000-0003-3917-9493
SPIN 代码: 6412-4801
Scopus 作者 ID: 231438

M.D., D.Sc. (Medicine), the Head of Assisted Reproductive Technologies Department

俄罗斯联邦, Saint Petersburg

Olesya Bespalova

Ott Research institute of obstetrics, gynecology and reproductology

Email: shiggerra@mail.ru
ORCID iD: 0000-0002-6542-5953
SPIN 代码: 4732-8089
Scopus 作者 ID: D-3880-2018

M.D., D.Sc. (Medicine), Professor, Deputy director for science

俄罗斯联邦, Saint Petersburg

参考

  1. Tapil’skaya NI, Budilovskaya OV, Krysanova AA, et al. Endometrial microbiota of women with chronic endometritis and idiopathic infertility. Obstetrics and Gynecology. 2020;(4):72–81. (In Russ.) doi: 10.18565/aig.2020.4.72 81
  2. Tapil’skaya NI, Gzgzyan AM, Kogan IY. Granulocyte colony-stimulating factor as a checkpoint of the embryo invasive potential and endometrial receptivity. Journal of Obstetrics and Women’s Diseases. 2019;68(1):83–92. (In Russ.) doi: 10.17816/JOWD68183-92
  3. Tapil’skaya NI, Dzhemlikhanova LKh, Krikheli IO, et al. Combined use of granulocyte colony stimulating factor in repeated implantation failure. Russian Journal of Human Reproduction. 2020;26(2):62–68. (In Russ.) doi: 10.17116/repro20202602162
  4. Abuwala N, Tal R. Endometrial stem cells: origin, biological function, and therapeutic applications for reproductive disorders. Curr Opin Obstet Gynecol. 2021;33(3):232–240. doi: 10.1097/GCO.0000000000000702
  5. Tapil’skaya NI. The role of the immune system in the pathogenesis of miscarriage. Prerequisites for pharmacological correction. Obzory po klinicheskoi farmakologii i lekarstvennoi terapii. 2002;1(2):15–26 (In Russ.)
  6. Kuznetsova IV, Zemlina NS, Musina RА, et al. The use of autologous mesenchymal stem cells for endometrial repair in patients with lower fertility. Gynecology, Obstetrics and Perinatology. 2019; 18(6): 34–40. (In Russ.) doi: 10.20953/1726-1678-2019-6-34-40
  7. Gharibeh N, Aghebati-Maleki L, Madani J, et al. Cell-based therapy in thin endometrium and Asherman syndrome. Stem Cell Res Ther. 2022;13(1):33. doi: 10.1186/s13287-021-02698-8
  8. Tolibova GKh, Tral’ TG, Kleshchev MA. Endometrial dysfunction: an algorithm for clinical and morphological studies. Saint Petersburg; 2016. 44 p. (In Russ.)

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