Bone Marrow Stem Cell Treatment for Asherman's Syndrome and Endometrial Atrophy

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Bone Marrow Stem Cell transplantation may improve Assisted Reproduction Techniques (ART) outcomes in refractive Asherman's Syndrome or Atrophic Endometrium.

Detailed Description
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This novel technique refers to the use of CD133+ autologous bone marrow stem-cells to regenerate the endometrium in patients with Asherman's Syndrome, Endometrial Atrophy or any condition that produce a destruction of the endometrium or its de novo creation in a bioengineered uterus. It requires a previous mobilization in the peripheral blood of CD133+ autologous bone marrow stem cells, subsequent apheresis and transplant of the same cells in the spiral arterioles of the uterus with the aim to regenerate de novo the endometrium. This technique represents a new therapeutical approach for the treatment of endometrial regeneration problems such Asherman Syndrome and the endometrial atrophy since currently no specific treatment for these endometrial pathologies exist. A prospective experimental non controlled study has been designed in order to assess the effectiveness of these technique as a new tool for treat Asherman's Syndrome and Endometrial Atrophy.

Official Title
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New Therapeutic Approaches to Treat Asherman's Syndrome and Endometrial Atrophy Based in BM Stem Cells Autologous Transplantation

Conditions
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Asherman's Syndrome, Endometrium; Atrophy, Cervix

Intervention / Treatment
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* Biological: Bone Marrow CD133+ Stem Cell Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed of Asherman Syndrome and absence of pregnancy after treatment Endometrial atrophy (<6mm) with Implantation Failure Age 20-45 years-old Normal liver, heart and kidney function Presence of menstrual bleeding with Natural Cycle or HRT Absence of psychiatric pathology and ability to accomplish the treatment β-hCG negative Absence of SDT Exclusion Criteria: Absence of peripheral vein access Lack of accomplish inclusion criteria

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Bone Marrow CD133+ Stem Cell Transplantation|Bone Marrow Stem Cell (BMSC) mobilization peripheral blood induced by granulocyte-CSF (G-CSF) 5 mcg/kg sc every 12 hours for 4 days. BMSC recollection with apheresis procedure and positive selection of the CD133+ cells. The selection procedure will be performed for a maximum of 3 hours or until at least 50 million cells are collected. CD133+ cells transplantation into the uterine spiral arterioles by intra-arterial catheterization Subsequently Hormonal Replacement Therapy (HRT) will be given to the patients Hysteroscopy will be performed 2-3 months after stem cell transplantation Embryo transfer will be performed 3-6 months after stem cell transplantation with HRT endometrial preparation|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live-birth rate | Live birth rate is the percentage of all cycles that lead to live birth, and is the pregnancy rate adjusted for miscarriages and stillbirths. | 15 months | 
| Ongoing pregnancy rate | Ongoing pregnancy rate is the percentage of all cycles that lead to presence of heartbeat in Ultrasound scan at the end of the first trimester | 9 months | 
| Implantation Rate | Implantation rate is the percentage of embryos which successfully undergo implantation compared to the number of embryos transferred in a given period. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrial thickness prior to the treatment | Endometrial thickness measured with Ultrasound in a previous treatment with Hormonal Replacement Therapy | 0 | 
| Endometrial Thickness after treatment | Endometrial thickness measured with Ultrasound with Hormonal Replacement Therapy 3-6 months after Bone Marrow Stem Cell Transplantation | 3-6 months |