Research Article

Application of autologous adipose-derived stem cells for thin endometrium treatment in patients with failed ART programs

I Sudoma, L Pylyp, Y Kremenska and Y Goncharova*

Published: 02/12/2019 | Volume 3 – Issue 1 | Pages: 001-008

Introduction

One of the factors of assisted reproduction technology (ART) success is an adequate growth and development of endometrium. At the end of follicular phase of menstrual cycle endometrium reaches its greatest thickness. It is believed that there is a critical limit of endometrial thickness beyond which the implantation of embryo is unlikely or impossible [1-5]. In practice of ART programs ultrasound measurement of endometrial thickness is used to evaluate uterine lining growth. Scientific literature is debatable as to what thickness of endometrium should be considered optimal, some researchers emphasize the negative impact of “thin endometrium” on the success of ART programs [1-12], while others do not agree [6,7,9]. Nevertheless, when endometrial thickness in ART program does not exceed 6 mm the chance of pregnancy occurring is very low (Kumbak B, et al. 2009). Endometrium is a unique tissue that has thousands of cycles of growth, differentiation and detachment during woman’s life [13-15]. Various organs and tissues are believed to contain stem cells populations that ensure the recovery of these tissues. Cells with multipotent properties were also found in endometrium [16,17]. A group of scientists from Australia detected and identified population of mesenchymal stem cells (MSCs) and epithelial progenitor cells in human endometrium [13,18-20]. It may be assumed that the absence, lack and defects of MSCs or the absence of signals needed to push their proliferation and differentiation lead to the fact that endometrium is not renewed, thin and unable to provide the implantation of embryo. Endometrial MSCs are adult stem cells similar to those found in other tissues. Therefore, in case of their lack or absence it is logical to assume that endometrial niche can be colonized by autologous stem cells derived from other tissues. In some areas of medicine, autologous stem cells are already used in clinical practice for the repair of damaged tissues and organs, although these methods are still experimental [21,22]. There were several publications about the use of stem cells for improving the endometrium growth and structure in experimental (animal) models (Zhao Jing et al. 2014) and in clinical practice in patients with Asherman syndrome and endometrial athrophy refractory to other types of therapy [23,24], (Singh N, et al. 2014; Santamariya X, et al. 2016). The main source of autologous stem cells is bone marrow. However, lately adipose tissue becomes popular because the procedure of its extraction – liposuction is less traumatic and better tolerated by patients compared to spongy bone puncture for bone marrow obtaining [25]. First MSCs were derived from adipose tissue during its cosmetic extraction in 2001 [26]. These adipose-derived mesenchymal stem cells (ASCs) have rather high capacity for differentiation (multipotency) and proliferation.

The aim of this work was to study the possibility of autologous ASCs use for the treatment of “thin endometrium” in patients with unsuccessful ART programs.

The protocol of treatment was approved by local ethical committee and patient’s informed consent was obtained for it.

Read Full Article HTMLDOI: 10.29328/journal.jsctt.1001013Cite this Article

References

  1. Check JH, Nowroozi K, Choe L, Dietterich C. The effect of endometrial thickness and echogenic patterns on pregnancy rates during in vitro fertilization. Fertil Steril. 1991; 56: 1173–1175. Ref.: https://goo.gl/aAvLmU
  2. Check JH, Nowroozi K, Choe J, Lurie D, Dietterich C. The effect of endometrial thickness and echo pattern on in vitro fertilization outcome in donor oocyte-embryo transfer cycle. Fertil Steril. 1993; 59; 72–75. Ref.: https://goo.gl/R9S3Ee
  3. Dickey RP, Olar TT, Curole DN, Taylor SN, Rye PH. Endometrial pattern and thickness associated with pregnancy outcome after assisted reproductive technologies. Hum Reprod. 1992; 7: 418–421. Ref.: https://goo.gl/QPx5S3
  4. Noyes N, Liu HC, Sultan K, Schattman G, Rosenwaks Z. Endometrial thickness appears to be a significant factor in embryo implantation in in-vitro fertilization. Hum Reprod. 1995; 10: 919–922. Ref.: https://goo.gl/f4qv5L
  5. Rinaldi L, Lisi F, Floccari A, Lisi R, Pepe G, et al. Endometrial thickness as a predictor of pregnancy after in-vitro fertilization but not after intracytoplasmic sperm injection. Hum Reprod. 1996; 11: 1538–1541. Ref.: https://goo.gl/aw9AfU
  6. Yuval Y, Lipitz S, Dor J, Achiron R. The relationships between endometrial thickness, and blood flow and pregnancy rates in in-vitro fertilization. Hum Reprod. 1999; 14: 1067–1071. Ref.: https://goo.gl/bPFSRG
  7. De Geyter C, Schmitter M, De Geyter M, Nieschlag E, Holzgreve W, et al. Prospective evaluation of the ultrasound appearance of the endometrium in a cohort of 1,186 infertile women. Fertil Steril. 2000; 73: 106-113. Ref.: https://goo.gl/ekZcCq
  8. Bassil S. Changes in endometrial thickness, width, length and pattern in predicting pregnancy outcome during ovarian stimulation in in vitro fertilization. Ultrasound Obstet Gynecol. 2001; 18: 258–263. Ref.: https://goo.gl/f1dGzH
  9. Schild RL, Knobloch C, Dorn C, Fimmers R, van der Ven H, et al.  Endometrial receptivity in an in vitro fertilization program as assessed by spiral artery blood flow, endometrial thickness, endometrial volume, and uterine artery blood flow. Fertil Steril. 2001; 75: 361–366. Ref.: https://goo.gl/dnMFV3
  10. Zhang X, Chen CH, Confino E, Barnes R, Milad M, et al. Increased endometrial thickness is associated with improved treatment outcome for selected patients undergoing in vitro fertilization–embryo transfer. Fertil Steril. 2005; 83: 336–340. Ref.: https://goo.gl/MR7bSQ
  11. Richter KS, Bugge KR, Bromer JG, Levy MJ. Relationship between endometrial thickness and embryo implantation, based on 1,294 cycles of in vitro fertilization with transfer of two blastocyst-stage embryos. Fertil Steril. 2007; 87: 53–59. Ref.: https://goo.gl/cAUXjp
  12. McWilliams GD, Frattarelli JL. Changes in measured endometrial thickness predict in vitro fertilization success. Fertil Steril. 2007; 8: 74-81. Ref.: https://goo.gl/mjLRVA
  13. Gargett CE. Uterine stem cells: What is the evidence? Hum Reprod. 2007; 13: 87–101. Ref.: https://goo.gl/EXicq4
  14. Ono M, Maruyama T, Yoshimura Y. Regeneration and adult stem cells in the human female reproductive tract. Stem Cell Clon. 2008; 1: 23–29. Ref.: https://goo.gl/Tr7tFf
  15. Maruyama T, Masuda H, Ono M, Kajitani T, Yoshimura Y. Human uterine stem/progenitor cells: their possible role in uterine physiology and pathology. Reprod. 2010; 140: 11–22. Ref.: https://goo.gl/rMTjsg
  16. Wolff EF, Wolff AB, Hongling Du, Taylor HS. Demonstration of multipotent stem cells in the adult human endometrium by in vitro chondrogenesis. Reprod Sci. 2007; 14: 524–533. Ref.: https://goo.gl/2H9zjR
  17. Cervelló I, Mirantes C, Santamaria X, Dolcet X, Matias-Guiu X, et al. Stem cells in human endometrium and endometrial carcinoma. Int J Gynecol Pathol. 2011; 30: 317–327. Ref.: https://goo.gl/m5Gtpj
  18. Gargett CE, Chan RWS, Scahwab KE. Endometrial stem cells. Curr Opin Obstet Gynecol. 2007; 19: 377–383. Ref.: https://goo.gl/Yq297f
  19. Gargett CE, Schwab KE, Zillwood RM, Nguyen HP, Wu D. Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium. Biol Reprod. 2009; 80: 1136–1145. Ref.: https://goo.gl/eV32Ex
  20. Gargett CE, Masuda H. Adult stem cells in the endometrium. Mol Hum Reprod. 2010; 16: 818–834. Ref.: https://goo.gl/69Q1Sr
  21. Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders. Nature. 2006; 441: 1094–1096. Ref.: https://goo.gl/iDgpXT
  22. Singec I, Jandial R, Crain A, Nikkhah G, Snyder EY. The leading edge of stem cell therapeutics. Annu Rev Med. 2007; 58: 313–328. Ref.: https://goo.gl/VDBKzm
  23. Nagori CB, Panchal SY, Patel H. Endometrial regeneration using autologous adult stem cells followed by conception by in vitro fertilization in a patient of severe Asherman’s syndrome. J Hum Reprod Sci. 2011; 4: 43–48. Ref.: https://goo.gl/ALX2CX
  24. Sudoma I, Kremenska Y, Pylyp L, Goncharova Y, Zadorozhnaja T, et al. The autologous fat stem cells in the treatment of the atrophic endometrium in women with infertility and the use of ART. Zdoroviye zhenshchiny. 2013; 4: 149-156.
  25. Ogawa R. The importance of adipose-derived stem cells and vascularized tissue regeneration in the field of tissue transplantation. Curr Stem Cell Res Ther. 2006; 1:13–20. Ref.: https://goo.gl/gijwtn
  26. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001; 7: 211–228. Ref.: https://goo.gl/66Kr2H
  27. Bernacki SH, Wall ME, Loboa EG. Isolation of human mesenchymal stem cells from bone and adipose tissue. Met Cell Biol. 2008; 86: 257– 278. Ref.: https://goo.gl/b9V6va
  28. Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy. 2013; 15: 641–648. Ref.: https://goo.gl/2e6ZCe
  29. Korbling M, Estrov Z. Adult stem cells for tissue repair—a new therapeutic concept? N Engl J Med. 2003; 349: 570–582. Ref.: https://goo.gl/c5SV3x  
  30. Du H, Taylor HS. Stem cells and reproduction. Curr Opin Obstet Gynecol. 2010; 22: 235–241. Ref.: https://goo.gl/C26k1B
  31. Salem HK, Thiemermann C. Mesenchymal stromal cells: current understanding and clinical status. Stem Cell. 2010; 28: 585–596. Ref.: https://goo.gl/XqemaE
  32. Sudoma I, Kremenska Y, Zukin V, Goncharova Y. Novel treatment for patients with thin endometrium? MSRM International meeting ―Implantation – Recurrent Miscarriages Science and Clinical Aspects, Crete, Greece, 2010; 24-26, 22–23.
  33. Sudoma I, Pylyp L, Goncharova Y, Zukin V. Endometrial regeneration with autologous adipose derived stem cells resulting in pregnancy with donated oocyte embryos. Hum Reprod. 2012; 27: 342–344. Ref.: https://goo.gl/QXMXDj
  34. Check JH, Cohen R. Live fetus following embryo transfer in a woman with diminished egg reserve whose maximal endometrial thickness was less than 4 mm. Clin Exp Obstet Gynecol. 2011; 38: 330–332. Ref.: https://goo.gl/y4op2p
  35. Dix E, Check JH. Successful pregnancies following embryo transfer despite very thin late proliferative endometrium. Fertil Steril. 2008; 89: 15–16. Ref.: https://goo.gl/Bygnf5
  36. Sundström P. Establishment of a successful pregnancy following in-vitro fertilization with an endometrial thickness of no more than 4 mm. Hum. Reprod. 1998; 13: 1550-1552. Ref.: https://goo.gl/og9hnQ