Autologous Bone Marrow-derived Mesenchymal Stem Cells for Atrophic Endometrium in Patients With Repeated IVF Failures
Condition: Infertility, Female; Infertility of Uterine Origin; Asherman Syndrome
MeSH terms: Infertility; Infertility, Female; Gynatresia
Study type: Interventional
Phase: Phase 2

Summary: 
      Investigators will examine safety and efficiency of the cell product of autologous bone
      marrow-derived mesenchymal stem cells (MSC) for patients with repeated IVF failures and
      hypoplastic or/and fibrosis process of endometrium
    

Detailed description: 
      Sixty patients eligible for the study will be divided to two groups (experimental and
      control) according to randomization (envelope) procedure in 1:1 ratio.

      For patients of the main group bone marrow stem cells will be extracted from the crest of the
      ilium using standard methodology. After extraction and cultivation final product of
      autologous bone marrow-derived mesenchymal stem cells will be transplanted to endometrial
      cavity on menstrual cycle day 5-6. Meanwhile patients will receive three cycles of hormonal
      replacement therapy (4 mg Progynova (Bayer Pharma, Germany) daily on menstrual cycle day 5-25
      in combination with 20 mg Duphaston (Abbott Healthcare Products, B.V., Netherlands) daily
      from day 15 to day 25. On day 20 of hormonal replacement therapy (HRT) of the last (third)
      cycle Pipelle-biopsy of endometrium will be performed. Obtained material will be analyzed by
      immunohistochemistry with the assessment of estrogen and progesterone receptors, VEGFa,
      GM-CSF, CD133+, CD34 and CD56. Ultrasound characteristics of endometrial quality will be
      registered on day 9-10 and day 19-21 of every cycle. When morphological and echographic
      parameters of endometrium are found satisfactory for embryo transfer, the HRT for endometrial
      preparation for frozen/thawed embryo transfer cycle will be initiated. If acceptable
      endometrial characteristics are not achieved, patients could be offered to undergo repeated
      (not more than 3) transplantation of MSC procedures.

      Control group will receive three standard cycles of HRT following hysteroscopy before
      frozen/thawed embryo transfer. If endometrial characteristics are found unsatisfactory,
      gestational surrogacy might be offered.
    

Intervention name(s): bone marrow-derived MSC and HRT; hormonal replacement therapy
Intervention type(s): Biological; Other
Intervention description(s): Transplantation procedure to endometrial cavity is performed with ultrasound guidance on menstrual cycle day 5-6 through uterine cervix using cater for embryo transfer with 1 ml of suspension containing 5 millions of autologous bone marrow-derived mesenchymal stem cells
Three cycles of HRT following MSC transplantation;
Pipelle-biopsy of endometrium on day 20 of hormonal replacement therapy of the last (third) cycle;
Frozen/thawed embryo transfer 3-6 months after transplantation.; standard treatment of hypoplastic endometrium or Asherman's syndrome:
Three cycles of HRT preceding frozen/thawed embryo transfer;
Frozen/thawed embryo transfer.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Repeated IVF failure; Stem cell