Hysteroscopic Injections of Autologous Endometrial Cells and Platelet-rich Plasma in Patients With Thin Endometrium

Study Overview
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Brief Summary
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The investigation is devoted to the study of the effect of the introduction of autologous platelet-rich plasma (PRP) on the thickness of the endometrium. It was found that the injection of PRP and endometrial cells resuspended in PRP into the endometrium of patients with thin endometrium leads to an increase in the proliferation of endometrial cells, and as a result, to an increase in its thickness.

Detailed Description
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The study enrolled 115 patients with thin endometrium (<7 mm at implantation window) and infertility. The cohort was divided into groups based on the treatment regimen. Group 1 (the control, n=30) underwent conservative therapy. Group 2 (n=42) received intraendometrial injections of autologous PRP instead of the conservative therapy. Group 3 (n=38) received identical injections after conservative therapy. Group 4 (n=5) received injections of the minimally manipulated autologous endometrial cells suspended in autologous PRP. Injections of PRP and endometrial cells suspended in autologous PRP into basal layer of endometrium facilitate the reconstitution by enhancing cell proliferation and angiogenesis.

Official Title
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Hysteroscopic Injections of Autologous Endometrial Cells and Platelet-rich Plasma in Patients With Thin Endometrium - a Pilot Study

Conditions
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Thin Endometrium

Intervention / Treatment
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* Procedure: Conservative therapy
* Biological: PRP injection
* Biological: Injection of PRP after conservative therapy
* Biological: Injection of PRP with endometrial cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-40 years Normal karyotype Normal karyotype of the partner Regular ovulatory and menstrual cycle Endometrium <7 mm thick as measured at implantation window Availability of ≥2 vitrified blastocysts of good quality History of implantation failure and/or embryo transfer (ET) cancellation due to insufficient endometrial thickness Exclusion Criteria: Pathospermia in partner Use of donor gametes Premature ovarian failure Internal genital anomalies Systemic blood diseases and coagulopathy Hemoglobin <100 g/L Platelets <100×109/L Antiplatelet/anticoagulant therapy recipient status

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The patients were divided into 4 groups depending on the substances introduced into the basal layer of the endometrium. Group 1 underwent conservative therapy. Group 2 received intraendometrial injections of autologous PRP instead of the conservative therapy. Group 3 received identical injections after conservative therapy. Group 4 received injections of the minimally manipulated autologous endometrial cells suspended in autologous PRP.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conservative therapy<br>This is Group 1, whose patients received electrical impulse therapy using a BTL-4000 Premium G device (BTL Medical Technologies, Czech Republic) starting from day 5-7 of menstrual cycle for 10-12 days daily. | Procedure: Conservative therapy<br>* Conservative therapy to which the patients were subjected was the effect of an electrical impulse<br>|
| Experimental: PRP injection<br>This is Group 2, whose patients received single intraendometrial injections of autologous PRP during proliferative phase (day 6-9) of menstrual cycle. | Biological: PRP injection<br>* This intervention consisted of injecting platelet-rich plasma (PRP) into the endometrium<br>|
| Experimental: Injection of PRP after conservative therapy<br>This is Group 3, whose patients received electrical impulse therapy identically with Group 1 during the first menstrual cycle. In the second cycle, the patients received autologous PRP injections identically with Group 2. | Biological: Injection of PRP after conservative therapy<br>* This intervention consisted of conducting conservative therapy with an electrical impulse and then injecting PRP inside the endometrium<br>|
| Experimental: Injection of PRP with endometrial cells<br>This is Group 4, whose patients received single intraendometrial injections of the minimally manipulated autologous endometrial cells suspended in autologous PRP during proliferative phase (day 6-9) of menstrual cycle. | Biological: Injection of PRP with endometrial cells<br>* This intervention consisted of injecting endometrial cells suspended in prp<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in endometrial thickness after treatment compared with control. | Ultrasonography measurements of endometrial thickness before and after the therapy and compare the thickness. Endometrial thickness measured in mm. | Baseline and 2 month | 
| The Doppler-assisted detection of the uterine spiral arteries | The number of identified vessels is counted and the percentage of detection frequency is calculated accordingly, adjusted for the McNemar's binomial test. Compare the rates of visualization of the uterine spiral arteries after therapy in all groups of patients. | 1 month | 
| Study of the effect of therapy on the onset of pregnancy | Investigation of the rates of clinical pregnancies and live births in all groups. After therapy, the number of clinical pregnancy and the number of live births were calculated. | 9 months | 
| The content of growth factor in autologous PRP | Investigation of the content of platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF) in autologous PRP. Relative levels of PDGF-BB and VEGF are normalized to the total protein content. | 3 month | 
| Phenotyping of cells isolated from endometrial biopsies | Investigation of cellular composition in endometrial biopsy. The percentage of cells positive for markers of mesenzymal stromal cells, epithelial and endothelial cells, lymphocytes is calculated and the determination of the phenotype of cells in endometrial biopsy. | 3 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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platelet-rich plasma, infertility, endometrial cells