Clinical Study of in Situ Regeneration of Endometrium

Study Overview
=================
Brief Summary
-----------------
Thin endometrium will lead to hypomenorrhea，infertility and recurrent pregnancy loss and there are few effective methods to increase the endometrial thickness and improve the fertility outcomes. Patients with thin endometrium will be divided into three groups and receive estrogen therapy, stem cell therapy and growth factor therapy respectively. This randomized controlled clinical study is carried out to explore the optimal treatment method and best indications for thin endometrium.

Official Title
-----------------
Clinical Study of in Situ Regeneration of Endometrium

Conditions
-----------------
Infertility, Female, of Uterine Origin, Endometrial Fibrosis

Intervention / Treatment
-----------------
* Drug: CBD-bFGF
* Drug: Collagen/BMMNCs
* Drug: Estrogen


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1.Patients with thin endometrium (4mm≤ EMT <7mm )or scarred endometrium (scarred area≤70%) which is nonresponsive to estrogen stimulation 2.Infertile patients with clear fertility desires 3.20-42 years old 4.Normal ovarian function or with frozen embryos 5.Willing to participate in follow-up Exclusion Criteria: Endometrial thickness <4mm or scarred endometrial area>70% Uterine cavity out of shape and the cavity depth<6.5mm Abnormal chromosome karyotype Uterine diseases including large intramural myomas, severe endometriosis, severe adenomyosis, severe congenital uterine malformations, endometrial tuberculosis, vaginitis and endometritis Systemic diseases: hypertension, diabetes, and so on Contraindications to pregnancy Contraindications to hormone replacement therapy Medical history of pelvic tumors or receiving pelvic radiotherapy 9 .Involved in other clinical studies 10. Unable to adhere to the follow-up

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 42 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBD-bFGF<br> | Drug: CBD-bFGF<br>* CBD-bFGF will be injected into the endometrium after hysteroscopy under the guidance of ultrasound<br>|
| Experimental: Collagen/BMMNCs<br> | Drug: Collagen/BMMNCs<br>* A collagen scaffold loaded with BMMNCs will be transplanted into the uterine cavity after hysteroscopy under the guidance of ultrasound<br>|
| Experimental: Estrogen<br> | Drug: Estrogen<br>* Patients will receive regular estrogen therapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrial thickness | Endometrial thickness evaluated by transvaginal sonography during late proliferative phase | 6 months | 
| Ongoing pregnancy rate | The presence of a living intrauterine fetus on TVU at the 12th week of gestation | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrial blood flow | Endometrial blood flow evaluated by transvaginal sonography | 6 months | 
| Pregnancy related complications | Miscarriage rate, live birth rate, ET cycle cancellation rate,Placenta related complications | 24 months | 
| Histological changes of endometrium | Histological changes of the thin endometrium before and after treatment | 12 months | 
| Menstrual blood volume | The change of menstrual blood volume after treatment compared with pre-treatment | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
thin endometrium, infertility