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Autologous Bone Marrow-derived Mesenchymal Stem Cells for Atrophic Endometrium in Patients With Repeated IVF Failures

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03166189
Recruitment Status : Completed
First Posted : May 25, 2017
Last Update Posted : January 2, 2020
Sponsor:
Information provided by (Responsible Party):
Valeria Muller, D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

Brief 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

Condition or disease Intervention/treatment Phase
Infertility, Female Infertility of Uterine Origin Asherman Syndrome Biological: bone marrow-derived MSC and HRT Other: hormonal replacement therapy Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Randomized Trial of Clinical Efficiency and Safety of Cell Product of Autologous Bone Marrow-derived Mesenchymal Stem Cells for Reparative Treatment of Destructively Changed Endometrium in Patients With Repeated IVF Failures
Actual Study Start Date : December 20, 2017
Actual Primary Completion Date : March 16, 2019
Actual Study Completion Date : December 28, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: bone marrow-derived MSC and HRT
endometrial injection of autologous cell product of MSC with hormonal replacement therapy before frozen/thawed ET
Biological: bone marrow-derived MSC and HRT
  • 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.

Active Comparator: hormonal replacement therapy
standard endometrial preparation for frozen/thawed ET
Other: hormonal replacement therapy

standard treatment of hypoplastic endometrium or Asherman's syndrome:

  • Three cycles of HRT preceding frozen/thawed embryo transfer;
  • Frozen/thawed embryo transfer.




Primary Outcome Measures :
  1. Assessment of endometrial receptivity [ Time Frame: 3-6 month after randomization ]
    combination of endometrial thickness on ultrasound and immunohistochemistry of endometrium assessed at the biopsy day of the third cycle of HRT


Secondary Outcome Measures :
  1. Clinical pregnancy rate [ Time Frame: 3-4 weeks after embryo transfer ]
    presence of intrauterine gestational sac at transvaginal ultrasound at 5-6 weeks of gestation or 5-6 weeks after starting the intervention; measured per frozen/thawed embryo transfer

  2. Treatment-Emergent Adverse Events [ Time Frame: 3-6 month after randomization ]
    Incidence of adverse events: side reactions, abdominal discomfort and patient's tolerance (Safety and Tolerability)



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 44 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Repeated IVF attempts with high and good quality embryo transfer in fresh and frozen IVF cycles;
  • Age 20-44 years;
  • Endometrial thickness less than 6 mm in 2 or more of HRT cycles for endometrial preparation for embryo transfer
  • Hysteroscopic evidence of fibrosis processes of uterine cavity with the absence of positive dynamics of HRT in 3 months following operation;
  • Signed informed consent.

Exclusion Criteria:

  • Contraindication for pregnancy;
  • Absence of cryopreserved embryos, stored at clinic's cryobank;
  • BMI > 30 kg/m2;
  • Impaired carbohydrate metabolism according to glucose tolerance test;
  • Thrombosis in anamnesis;
  • Oncological diseases in anamnesis;
  • Diagnosed inherited thrombophilia;
  • Uterine fibroids of more than 4 cm or more than 2 fibroids of 2.5 cm diameter;
  • Nodal form of adenomiosis;
  • Ovarian cysts more than 4 cm in diameter.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03166189


Locations
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Russian Federation
D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
Saint Petersburg, Russian Federation, 199034
Sponsors and Collaborators
D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
Investigators
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Principal Investigator: Alexandr Gzgzyan, Prof, PhD D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
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Responsible Party: Valeria Muller, PhD, Medical Doctor of Assisted Reproduction Technologies department, D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
ClinicalTrials.gov Identifier: NCT03166189    
Other Study ID Numbers: MSC-001
First Posted: May 25, 2017    Key Record Dates
Last Update Posted: January 2, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Valeria Muller, D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology:
Repeated IVF failure
Stem cell
Additional relevant MeSH terms:
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Infertility
Infertility, Female
Gynatresia