Transplantation of hAMSCs for Woman With DOR

Study Overview
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Brief Summary
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Patients with Diminished ovarian response (DOR）have a poor in vitro fertilization（IVF） outcome, and is considered one of most challenging tasks in artificial reproductive treatment (ART). Stem cell therapies are rapidly progressing fields and have shown promise in treatment of lots of disease, including aging and premature ovarian failure. The purpose of this study is to determine the safety and efficacy of intra vein injection of human Amniotic Mesenchymal Stem Cells(hAMSCs) in women suffered from infertility caused by DOR.

Detailed Description
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Patients with Diminished ovarian response (DOR）have a poor in vitro fertilization（IVF） outcome, and is considered one of most challenging tasks in artificial reproductive treatment (ART). Stem cell therapies are rapidly progressing fields and have shown immense promise in the treatment of lots of disease, including aging and premature ovarian failure. The purpose of this study is to determine the safety and efficacy of intra vein injection of human amniotic mesenchymal stem cells(hAMSCs) in women suffered from infertility caused by DOR. The hAMSCs were isolated and cultured in vitro and qualified by National Institutes for Food and Drug Control, China. The serum of each patient was kept and sent for laboratory test before the transplantation. The biomarkers of hAMSCs were detected again before transplantation. The hAMSCs were transplanted via venous in the dorsum of hand. The outcomes of patients were examined during and after the injection. The patients are monitored for hormones, follicles stimulated with minimal stimulation, number of oocyte retrieval and embryos In Vitro Fertilization (IVF).

Official Title
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The Safety and Efficacy Assessment of Human Amniotic Mesenchymal Stem Cells(hAMSCs) Transplantation in Woman With Diminished Ovarian Reserve (DOR)

Conditions
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Diminished Ovarian Response

Intervention / Treatment
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* Other: stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women between35 and 45 years, who is diagnosed with Diminished Ovarian Reserve by Bologna criteria, (AFC≤7，or serum AMH level < 1.10ng/ml), and failed pregnancies in at least two cycles of In Vitro Fertilization(IVF) or Intracytoplasmic Sperm Injection(ICSI). Willing to sign the Informed Consent Form. Exclusion Criteria: Patients diagnosed with hereditary, immunological and iatrogenic premature ovarian failure Patients allergy to blood products Patients diagnosed with abnormal coagulation function Patients diagnosed with uterine malformation Patients undergoing Preimplantation Genetic Testing Patients diagnosed with hydrosalpinx Patients diagnosed with infectious diseases Contraindications for In Vitro Fertilization-Embryo Transfer(IVF-ET) or pregnancy Prior personal history of stem cell clinical trail or other clinical trails Unwilling to comply with study protocol Patients identified with high risk for stem cell injection

Ages Eligible for Study
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Minimum Age: 35 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hAMSCs injection<br>hAMSCs were injected via venous in the dorsum of hand. | Other: stem cells<br>* hAMSCs injection via venous in the dorsum of hand<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability after hAMSCs injection. | Safety and tolerability assessed by Adverse Events and serious during injection and adverse events (SAEs) after injection assessed by long term follow-up . | Up to 12 months after first hAMSCs injection | 
| The ratio of transplantable embryo in DOR patients after hAMSCs injection. | The ratio of transplantable embryo to normal fertilized embryos in DOR patients after hAMSCs injection. | Up to 12 months after first hAMSCs injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ovarian function in DOR patients after hAMSCs injection. | Anti-müllerian Hormone (AMH) serum level, Follicle Stimulating Hormone (FSH) serum level, Estradiol (E2) serum level, Luteinizing Hormone (LH)serum level on menstrual day 2/3 will be evaluated after injection. The number of antral follicles will be recorded by transvaginal ultrasound scan. | Up to 12 months after first hAMSCs injection | 
| Outcomes of IVF in DOR patients after hAMSCs injection. | The number of oocyte retrieval, fertilization rate , blastocyst formation rate, implantation rate, incidence of clinical pregnancy rate, after hAMSCs injection. | Up to 12 months after first hAMSCs injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diminished ovarian response, human Amniotic Mesenchymal Stem Cells, Cell therapy