Human Amniotic Epithelial Cells for Asherman's Syndrome

Study Overview
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Brief Summary
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This project aims to investigate the safety and effectiveness of human amniotic epithelial cells in the treatment of the severe refractory Asherman's syndrome.

Detailed Description
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Asherman's syndrome is a gynecological disorder caused by the destruction of the endometrium due to repeated or aggressive curettages and/or endometritis. As a result, there is a loss of functional endometrium in multiple areas and the uterine cavity is obliterated by intrauterine adhesions, which results in amenorrhea, hypomenorrhea, infertility and recurrent pregnancy loss. Transcervical resection of adhesion (TCRA) is the main treatment for Asherman's syndrome, so far the effect is usually poor in moderate to severe refractory cases. Human amniotic epithelial cells (hAECs) are derived from human amniotic epithelium. hAECs retain the characteristics approximating to embryonic stem cells. Animal experiments have shown that the endometrial thickness and fertility of mice were significantly improved after intrauterine therapy with amniotic epithelial cells. To further explore the role of hAECs in Asherman's syndrome patients, this project plans to evaluate the safety of hAECs provided by Chongqing iCELL Biotechnology Co.,Ltd., which is a subsidiary of Shanghai iCELL Biotechnology Co.,Ltd., and find an effective treatment protocol.

Official Title
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Safety and Therapeutic Effect of Human Amniotic Epithelial Cells in Severe Refractory Asherman's Syndrome

Conditions
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Asherman's Syndrome

Intervention / Treatment
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* Biological: hAECs
* Biological: biological amnion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Hysteroscopy examination confirms intrauterine adhesions, II -III according to the American Fertility Society (AFS) classification of uterine adhesions; 2. Regular Menstrual cycles and menstruation is normal before abortion or curettage; 3. Having a clear desire to fertility; 4. Normal blood coagulation, liver, heart, and kidney function, absence of HIV, Hepatitis B or C, syphilis and psychiatric pathology; 5. Serum β-hCG is negative; 6. Be willing to complete the study and sign the consent form. Exclusion Criteria: 1. Having a history of malignant tumor; 2. Having other uterine diseases, such as, uterine fibroids, adenomyosis and uterine malformations; 3. Hysteroscopic adhesiolysis more than 3 times in the past; 4. Absence of peripheral vein access.

Ages Eligible for Study
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Minimum Age: 20 Years
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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: biological amnion loaded with hAECs<br>Biological amnion loaded with 100 million hAECs is placed into uterine cavity immediately after TCRA. | Biological: hAECs<br>* hAECs are provided by Chongqing iCELL Biotechnology Co.,Ltd., which is a subsidiary of Shanghai iCELL Biotechnology Co.,Ltd. The participants are blind to their arms because the surgery is done under anesthesia. After hysteroscopic adhesiolysis, subsequently oral antibiotics will be given for 3 days to prevent infection. Estrogen will be administrated for 3 cycles to stimulate the repair of endometrium after the surgery.<br>|
| Placebo Comparator: biological amnion<br>Biological amnion is placed into uterine cavity immediately after TCRA. | Biological: biological amnion<br>* Biological amnion is purchased from JiangXi RuiJi BioTechnology Co.,Ltd. The participants are blind to their arms because the surgery is done under anesthesia. After hysteroscopic adhesiolysis, subsequently oral antibiotics will be given for 3 days to prevent infection. Estrogen will be administrated for 3 cycles to stimulate the repair of endometrium after the surgery.<br>|
| Experimental: intravenous infusion of hAECs<br>intravenous infusion of 100 million hAECs immediately after TCRA | Biological: hAECs<br>* hAECs are provided by Chongqing iCELL Biotechnology Co.,Ltd., which is a subsidiary of Shanghai iCELL Biotechnology Co.,Ltd. The participants are blind to their arms because the surgery is done under anesthesia. After hysteroscopic adhesiolysis, subsequently oral antibiotics will be given for 3 days to prevent infection. Estrogen will be administrated for 3 cycles to stimulate the repair of endometrium after the surgery.<br>|
| Experimental: intrauterine infusion of hAECs<br>100 million hAECs is infused into uterine cavity immediately after TCRA. | Biological: hAECs<br>* hAECs are provided by Chongqing iCELL Biotechnology Co.,Ltd., which is a subsidiary of Shanghai iCELL Biotechnology Co.,Ltd. The participants are blind to their arms because the surgery is done under anesthesia. After hysteroscopic adhesiolysis, subsequently oral antibiotics will be given for 3 days to prevent infection. Estrogen will be administrated for 3 cycles to stimulate the repair of endometrium after the surgery.<br>|
| Experimental: hydrogel loaded with hAECs<br>Hydrogel loaded with 100 million hAECs is infused into uterine cavity immediately after TCRA. | Biological: hAECs<br>* hAECs are provided by Chongqing iCELL Biotechnology Co.,Ltd., which is a subsidiary of Shanghai iCELL Biotechnology Co.,Ltd. The participants are blind to their arms because the surgery is done under anesthesia. After hysteroscopic adhesiolysis, subsequently oral antibiotics will be given for 3 days to prevent infection. Estrogen will be administrated for 3 cycles to stimulate the repair of endometrium after the surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Menstrual blood volume | Estimate the menstrual blood volume after surgery by the number of sanitary napkins per day and number of days, which will be compared with pre-operation. | at 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrial thickness | Measure the endometrial thickness during periovulatory period on ultrasound by the same trained medical sonographers at 3 months after surgery, compared with pre-operation. | at 3 months | 
| Uterine volume | Measure the uterine volume during periovulatory period on ultrasound by the same trained medical sonographers at 3 months after surgery, compared with pre-operation. | at 3 months | 
| Ongoing pregnancy rate | A ongoing pregnancy means that at the 12th week of pregnancy, ultrasound reveals that the fetus had a heart beat and the size of the fetus is in consistent with the gestational week. | up to 24 months |