Increased endometrial thickness and improved reproductive outcomes in patients with thin endometrium, infertility and failed assisted reproduction after administration of secretome of peripheral blood mononuclear cells in suppositories

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Endometrial thickness (ET) <8 mm has an unfavorable impact on perinatal outcomes. One of the areas in treatment for thin endometrium is the use of cellular technologies that influence the reparative process, such as autologous platelet-rich plasma, peripheral blood mononuclear cells (PBMCs). The use of acellular secretome is a new trend with similar therapeutic properties that has been developed in regenerative medicine.

Objective: To evaluate the effect of secretome of peripheral blood mononuclear cells (SPBMC) on ET in women with thin endometrium and infertility.

Materials and methods: The study included 252 reproductive-aged infertile patients with a previous history of two or more attempts of assisted reproduction and the presence of thin endometrium not responding to therapy using other methods. In addition to the standard therapy, the patients received SPBMC Superlymph 25 units one suppository vaginally at night for 20 days from the 5th to the 25th day of the menstrual cycle from 1 to 3 months until there were satisfactory parameters of ET (8 mm or more) confirmed by ultrasound. All patients had a single cryopreserved embryo transfer performed.

Results: The statistical analysis of the data (n=252) showed a significant increase in ET to 8 mm or more in 80.2% of patients compared to the initial values. The effectiveness of assisted reproduction was as follows: the overall rate of clinical pregnancy per transfer was 38.1% (105/247), namely 47.2% (17/36) in patients aged 18–29, 39.8% (37/93) in patients aged 30–35, 38.5% (37/96) in patients aged 36–40, and 13.6% (3/22) in patients aged 41–45. The birth rate was 35.3% (36/102), namely 36.8% (7/19) in patients aged 18-29, 42.2% (19/45) in patients aged 30-35, and 27.8% (10/36) in patients aged 36-40.

Conclusion: The use of SPBMC in combination with standard therapy increases endometrial thickness, improves pregnancy and live birth rates in patients with thin endometrium and infertility.

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作者简介

Nadezhda Erlikhman

Istochnik IVF Clinic

编辑信件的主要联系方式.
Email: nadyaerlih@mail.ru
ORCID iD: 0009-0002-7011-6888

PhD, Deputy Chief Physician, Chief IVF Specialist, Obstetrician-Gynecologist, Ultrasound specialist

俄罗斯联邦, Chelyabinsk

Alexandr Yakovlev

Biotechfarm LLC

Email: nadyaerlih@mail.ru
ORCID iD: 0009-0000-3062-2159

Director for Medical Research

俄罗斯联邦, Moscow

参考

  1. Hou X., Liu Y., Streuli I., Dällenbach P., Dubuisson J., Ansaldi Y. et al. Endometrial regeneration in Asherman's syndrome: clinical and translational evidence of stem cell therapies. Curr. Stem Cell Res. Ther. 2019; 14(6): 454-9. https://dx.doi.org/10.2174/1574888X14666190213100528
  2. Mahajan N., Sharma S. The endometrium in assisted reproductive technology: How thin is thin? J. Hum. Reprod. Sci. 2016; 9(1): 3-8. https:// dx.doi.org/10.4103/0974-1208.178632
  3. Craciunas L., Gallos I., Chu J., Bourne T., Quenby S., Brosens J.J. et al. Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis. Hum. Reprod. Update. 2019; 25(2): 202-23. https://dx.doi.org/10.1093/humupd/dmy044
  4. Eftekhar M., Tabibnejad N., Tabatabaie A.A. The thin endometrium in assisted reproductive technology: an ongoing challenge. Middle East Fertil. Soc. J. 2018; 23(1): 1-7. https://dx.doi.org/10.1016/j.mefs.2017.12.006
  5. Liu K.E., Hartman M., Hartman A. Management of thin endometrium in assisted reproduction: a clinical practice guideline from the Canadian Fertility and Andrology Society. Reprod. Biomed. Online. 2019; 39(1): 49-62. https://dx.doi.org/10.1016/j.rbmo.2019.02.013
  6. Mahutte N., Hartman M., Meng L., Lanes A., Luo Z.C., Liu K.E. Optimal endometrial thickness in fresh and frozen-thaw in vitro fertilization cycles: an analysis of live birth rates from 96,000 autologous embryo transfers. Fertil. Steril. 2022; 117(4): 792-800. https://dx.doi.org/10.1016/j.fertnstert.2021.12.025
  7. Ganer Herman H., Volodarsky-Perel A., Ton Nu T.N., Machado-Gedeon A., Cui Y., Shaul J. et al. Pregnancy complications and placental histology following embryo transfer with a thinner endometrium. Hum. Reprod. 2022; 37(8): 1739-45. https://dx.doi.org/10.1093/humrep/deac148
  8. Zhao Y., Liu D., Liu N., Li Y., Yao Z., Tian F. et al. An endometrial thickness < 8 mm was associated with a significantly increased risk of EP after freeze-thaw transfer: an analysis of 5,960 pregnancy cycles. Front. Endocrinol. (Lausanne). 2022; 13: 884553. https://dx.doi.org/10.3389/fendo.2022.884553
  9. Oron G., Hiersch L., Rona S., Prag-Rosenberg R., Sapir O., Tuttnauer-Hamburger M. et al. Endometrial thickness of less than 7.5 mm is associated with obstetric complications in fresh IVF cycles: a retrospective cohort study. Reprod. Biomed. Online. 2018; 37(3): 341-8. https://dx.doi.org/10.1016/ j.rbmo.2018.05.013
  10. Ranisavljevic N., Raad J., Anahory T., Grynberg M., Sonigo C. Embryo transfer strategy and therapeutic options in infertile patients with thin endometrium: a systematic review. J. Assist. Reprod. Genet. 2019; 36(11): 2217-31. https://dx.doi.org/10.1007/s10815-019-01576-w
  11. Critchley H.O.D., Maybin J.A., Armstrong G.M., Williams A.R.W. Physiology of the endometrium and regulation of menstruation. Physiol. Rev. 2020; 100(3): 1149-79. https://dx.doi.org/10.1152/physrev.00031.2019
  12. Sheikhansari G., Pourmoghadam Z., Danaii S., Mehdizadeh A., Yousefi M. Etiology and management of recurrent implantation failure: A focus on intra-uterine PBMC-therapy for RIF. J. Reprod. Immunol. 2020; 139: 103121. https://dx.doi.org/10.1016/j.jri.2020.103121
  13. Gharibeh N., Aghebati-Maleki L., Madani J., Pourakbari R., Yousefi M., Ahmadian Heris J. Cell-based therapy in thin endometrium and Asherman syndrome. Stem Cell Res. Ther. 2022; 13(1): 33. https://dx.doi.org/10.1186/s13287-021-02698-8
  14. Turinetto V., Vitale E., Giachino C. Senescence in human mesenchymal stem cells: functional changes and implications in stem cell-based therapy. Int. J. Mol. Sci. 2016; 17(7):1164. https://dx.doi.org/10.3390/ijms17071164
  15. Zhou Y., Yamamoto Y., Xiao Z., Ochiya T. The immunomodulatory functions of mesenchymal stromal/stem cells mediated via paracrine activity. J. Clin. Med. 2019; 8(7): 1025. https://dx.doi.org/10.3390/jcm8071025
  16. Kusuma G.D., Carthew J., Lim R., Frith J.E. Effect of the microenvironment on mesenchymal stem cell paracrine signaling: opportunities to engineer the therapeutic effect. Stem Cells Dev. 2017; 26(9): 617-31. https:// dx.doi.org/10.1089/scd.2016.0349
  17. Haque N., Abdullah B.J.J., Kasim N.H.A. Secretome: pharmaceuticals for cell-free regenerative therapy In: Pham P.V., ed. Stem Cell Drugs - a New Generation of Biopharmaceuticals. Springer; 2018: 17-35. https://dx.doi.org/10.1007/978-3-319-99328-7_2
  18. Gugerell A., Sorgenfrey D., Laggner M., Raimann J., Peterbauer A., Bormann D. et al. Viral safety of APOSECTM: a novel peripheral blood mononuclear cell derived-biological for regenerative medicine. Blood Transfus. 2020; 18(1): 30-9. https://dx.doi.org/10.2450/2019.0249-18
  19. Vizoso F.J., Eiro N., Cid S., Schneider J., Perez-Fernandez R. Mesenchymal stem cell secretome: toward cell-free therapeutic strategies in regenerative medicine. Int. J. Mol. Sci. 2017; 18(9): 1852. https://dx.doi.org/10.3390/ijms18091852
  20. Daneshmandi L., Shah S., Jafari T., Bhattacharjee M., Momah D., Saveh-Shemshaki N. et al. Emergence of the stem cell secretome in regenerative engineering. Trends Biotechnol. 2020; 38(12): 1373-84. https:// dx.doi.org/10.1016/j.tibtech.2020.04.013
  21. Bormann D., Gugerell A., Ankersmit H.J., Mildner M. Therapeutic application of cell secretomes in cutaneous wound healing. J. Invest. Dermatol. 2023; 143(6): 893-912. https://dx.doi.org/10.1016/j.jid.2023.02.019
  22. Mildner C.S., Copic D., Zimmermann M., Lichtenauer M., Direder M., Klas K. et al. Secretome of stressed peripheral blood mononuclear cells alters transcriptome signature in heart, liver, and spleen after an experimental acute myocardial infarction: an in silico analysis. Biology (Basel). 2022; 11(1): 116. https:// dx.doi.org/10.3390/biology11010116
  23. Средство для иммуностимуляции. Российский патент 2000 г. по МПК A61K35/14 A61K38/19 RU2145500C1; Патент N 1494274 от 20.03.97. «Способ получения фактора, ингибирующего миграцию макрофагов и лейкоцитов», Ганковская Л.В., Ковальчук Л.В. [Agent for immunostimulation. 2000 Russian IPC patent A61K35/14 A61K38/19 RU2145500C1; Patent N 1494274, dated 20.03.97. "Method of obtaining a factor inhibiting macrophage and leukocyte migration", Gankovskaya L.V., Kovalchuk L.V. (in Russian)].
  24. Гиляров М.С., ред. Биологический энциклопедический словарь. М.: Советская энциклопедия; 1986. 831 с. [Gilyarov M.S., ed. Biological encyclopedic dictionary. Moscow: Soviet Encyclopedia; 1986. 831 p. (in Russian)].
  25. Доброхотова Ю.Э., Ганковская Л.В., Боровкова Е.И., Зайдиева З.С., Скальная В.С. Модулирование локальной экспрессии факторов врожденного иммунитета у пациенток с хроническим эндометритом и бесплодием. Акушерство и гинекология. 2019; 5: 125-32. [Dobrokhotova Yu.E., Gankovskaya L.V., Borovkova E.I., Zaidieva Z.S., Skalnaya V.S. Modulation of the local expression of innate immune factors in patients with chronic endometritis and infertility. Obstetrics and Gynecology. 2019; (5): 125-32. (in Russian)]. https://dx.doi.org/10.18565/aig.2019.5.125-132
  26. Доброхотова Ю.Э., Боровкова Е.И., Нугуманова О.Р. Улучшение процессов ангиогенеза и репродуктивных исходов у пациенток с хроническим эндометритом. Акушерство и гинекология. 2021; 3: 145-52. [Dobrokhotova Yu.E., Borovkova E.I., Nugumanova O.R. Improvement of angiogenesis and reproductive outcomes in patients with chronic endometritis. Obstetrics and Gynecology. 2021; (3): 145-52 (in Russian)]. https:// dx.doi.org/10.18565/aig.2021.3.145-152
  27. Тапильская Н.И., Толибова Г.Х., Савичева А.М., Копылова А.А., Глушаков Р.И., Будиловская О.В., Крысанова А.А., Горский А.Г., Гзгзян А.М., Коган И.Ю. Эффективность локальной цитокинотерапии хронического эндометрита пациенток с бесплодием. Акушерство и гинекология. 2022; 2: 91-100. [Tapilskaya N.I., Tolibova G.Kh., Savicheva A.M., Kopylova A.A., Glushakov R.I., Budilovskaya O.V., Krysanova A.A., Gorskii A.G., Gzgzyan A.M., Kogan I.Yu. The effectiveness of local cytokine therapy for chronic endometritis in patients with infertility. Obstetrics and Gynecology. 2022; (2): 91-100. (in Russian)]. https://dx.doi.org/10.18565/ aig.2022.2.91-100
  28. Zheng Y., Chen B., Dai J., Xu B., Ai J., Jin L. et al. Thin endometrium is associated with higher risks of preterm birth and low birth weight after frozen single blastocyst transfer. Front. Endocrinol. (Lausanne). 2022; 13: 1040140. https://dx.doi.org/10.3389/fendo.2022.1040140
  29. Дикке Г.Б., Суханов А.А., Остроменский В.В., Кукарская И.И. Течение и исходы беременности у пациенток с хроническим эндометритом и нарушением репродуктивной функции, получавших комплексное лечение с использованием препарата «Суперлимф» (рандомизированное контролируемое испытание в параллельных группах «ТЮЛЬПАН»). Акушерство и гинекология. 2023; 4: 132-44. [Dikke G.B., Sukhanov A.A., Ostromensky V.V., Kukarskaya I.I. Course and outcomes of pregnancy in patients with chronic endometritis and impaired reproductive function after receiving complex treatment with drug Superlymph: randomized control trial in parallel groups “TULIP”. Obstetrics and Gynecology. 2023; (4): 132-44 (in Russian)]. https://dx.doi.org/10.18565/aig.2023.74
  30. Суханов А.А., Дикке Г.Б., Остроменский В.В., Кукарская И.И., Шилова Н.В. Течение и исходы беременности, наступившей в результате экстракорпорального оплодотворения, у пациенток с хроническим эндометритом, получавших комплексное лечение с использованием препарата «Суперлимф» на прегравидарном этапе (рандомизированное контролируемое испытание «ТЮЛЬПАН 2»). Акушерство и гинекология. 2023; 8: 123-34. [Sukhanov A.A., Dikke G.B., Ostromensky V.V., Kukarskaya I.I., Shilova N.V. Course and outcomes of pregnancy following IVF in patients with chronic endometritis receiving complex treatment with the Superlymph medication at the preconception stage (TULIP 2 randomized controlled trial). Obstetrics and Gynecology. 2023; (8): 123-34 (in Russian)]. https://dx.doi.org/10.18565/aig.2023.190
  31. Watters M., Martínez-Aguilar R., Maybin J.A. The menstrual endometrium: from physiology to future treatments. Front. Reprod. Health. 2022; 3: 794352. https://dx.doi.org/10.3389/frph.2021.794352
  32. Zhang X., Li Y., Chen X., Jin B., Shu C., Ni W. et al. Single-cell transcriptome analysis uncovers the molecular and cellular characteristics of thin endometrium. FASEB J. 2022; 36(3): e22193. https://dx.doi.org/10.1096/fj.202101579R
  33. Kabashima K. Unveiling dynamic interactions: in vivo imaging chronicles inflammation and regeneration in living organisms. Inflamm. Regen. 2023; 43(1): 61. https://dx.doi.org/10.1186/s41232-023-00312-3
  34. Qiu T., Pochopień M., Hanna E., Liang S., Wang Y., Han R. et al. Challenges in the market access of regenerative medicines, and implications for manufacturers and decision-makers: a systematic review. Regen. Med. 2022; 17(3): 119-39. https://dx.doi.org/10.2217/rme-2021-0083
  35. He Y., Tang R., Yu H., Mu H., Jin H., Dong J. et al. Comparative effectiveness and safety of 36 therapies or interventions for pregnancy outcomes with recurrent implantation failure: a systematic review and network meta-analysis. J. Assist. Reprod. Genet. 2023; 40(10): 2343-56. https://dx.doi.org/10.1007/ s10815-023-02923-8
  36. Maleki-Hajiagha A., Razavi M., Rezaeinejad M., Rouholamin S., Almasi-Hashiani A., Pirjani R. et al. Intrauterine administration of autologous peripheral blood mononuclear cells in patients with recurrent implantation failure: A systematic review and meta-analysis. J. Reprod. Immunol. 2019; 131: 50-6. https://dx.doi.org/10.1016/j.jri.2019.01.001
  37. Beer L., Mildner M., Gyöngyösi M., Ankersmit H.J. Peripheral blood mononuclear cell secretome for tissue repair. Apoptosis. 2016; 21(12): 1336-53. https:// dx.doi.org/10.1007/s10495-016-1292-8

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