Mesenchymal Stem Cells (MSCs) - Like Cell Transplantation in Women With Primary Ovarian Insufficiency

Study Overview
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Brief Summary
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There is a high incidence of women suffering from Primary Ovarian Insufficiency (POI). So far, there was no treatment sufficient enough to cure POI. Cell therapy is a rapidly developing field and have shown immense promise in the treatment of ovarian dysfunction. In this study, the investigator will evaluate the safety of MSC-like cell therapy in women suffering from POI.

Detailed Description
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The purpose of this work is to explore the safety and preliminary efficacy of human embryonic stem cell derived MSC-like cell transplantation in women with POI. MSC-like cells were injected directly into bilateral ovaries under transvaginal ultrasound. Patients are subjected into 3 groups, with low (0.2×107), medium (0.5×107) and high dosage (1.0×107) of cells injection for each ovary. The outcomes of patients were followed after the injection every 2 weeks. The investigator mainly follow the safety indexes, and the level of sex hormone and signs of follicle growth will also be monitored. The growing follicles will be stimulated by exogenous hormone, followed by oocyte retrieval and in vitro fertilization (IVF).

Official Title
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Safety Study of Human Embryonic Stem Cell Derived Mesenchymal Stem Cell (MSC)-Like Cells Transplantation in Women With Primary Ovarian Insufficiency (POI)

Conditions
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Primary Ovarian Insufficiency

Intervention / Treatment
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* Genetic: Cell therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Under 40 years of age; Have established regular menstrual cycle, oligomenorrhea / amenorrhea ≥ 4 months; FSH (Follicle-Stimulating Hormone) > 25 IU/mL; Bilateral ovaries are visible by ultrasound; Have fertility requirement, husband has sperms; Willing to sign the Informed Consent Form. Exclusion Criteria: Primary amenorrhea; History of serious drug allergy or allergic constitution; Thrombophlebitis and thromboembolia, past and present; Acute or chronic infection, hematologic disease, angiocardiopathy, pulmonary disease, liver disease, nephropathy, pancreas disease Autoimmune disease, history of severe familial genetic disease, etc. Anatomical abnormality of reproductive system; Contraindications for pregnancy; Spouse azoospermia; HIV+, hepatitis B, C; Thyroid dysfunction; History of previous malignant or ovarian tumors, history of ovarian therapy; Abnormal karyotyping (e.g. turner syndrome, fragile X syndrome); During pregnancy or lactation; Alcohol or other substance abuse; Mental disease, communicate obstruction; Unwilling to comply with follow-up schedule or want to take other treatment during the follow-up period; Attending doctor consider inappropriate to take part in.

Ages Eligible for Study
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Maximum Age: 40 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Patients will be subjected into 3 groups, with a low (0.2×107), medium (0.5×107) and high dosage (1.0×107) of cells transplantation for each ovary. The investigator will first carry out the low dosage group, and then the medium dosage group, based on the safety evaluation of the previous group, the high dosage group will be executed in the same way.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dosage<br>The low dosage will inject 2 million MSC-like cells (in 100ul suspension) for each ovary. | Genetic: Cell therapy<br>* Ovary injection with MSC-like cells through transvaginal ultrasound,3 injection points for each ovary.<br>|
| Experimental: Medium dosage<br>The medium dosage will inject 5 million MSC-like cells (in 100ul suspension) for each ovary. | Genetic: Cell therapy<br>* Ovary injection with MSC-like cells through transvaginal ultrasound,3 injection points for each ovary.<br>|
| Experimental: High dosage<br>The high dosage will inject 10 million MSC-like cells (in 100ul suspension) for each ovary. | Genetic: Cell therapy<br>* Ovary injection with MSC-like cells through transvaginal ultrasound,3 injection points for each ovary.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Temperature | Body temperature of the participants will be measured fortnightly after injection. | 0-24 weeks | 
| Pulse | Pulse of the participants will be measured fortnightly after injection. | 0-24 weeks | 
| Breaths per minute | Breathing rate of the participants will be measured fortnightly after injection. | 0-24 weeks | 
| Blood pressure | Both systolic pressure and diastolic pressure of the participants will be assessed fortnightly after injection. | 0-24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of antral follicle | The number of antral follicles developing will be recorded by transvaginal ultrasound fortnightly after injection. | 0-24 weeks | 
| Follicle-stimulating hormone (FSH) serum level | Serum FSH level will be tested fortnightly after injection. | 0-24 weeks | 
| Estradiol (E2) serum level | Serum E2 level will be tested fortnightly after injection. | 0-24 weeks | 
| Anti-Mullerian hormone (AMH) serum level | Serum AMH level will be tested fortnightly after injection. | 0-24 weeks | 
| Ovarian volume | The ovarian volume will be recorded fortnightly by transvaginal ultrasound after injection. | 0-24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stem cell, Transplantation, Human embryonic stem cell, Premature ovarian failure