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Autologous Platelet-Rich Plasma (PRP) and Endometrial Thickness

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ClinicalTrials.gov Identifier: NCT03067623
Recruitment Status : Recruiting
First Posted : March 1, 2017
Last Update Posted : May 23, 2019
Sponsor:
Information provided by (Responsible Party):
Roberta Venturella, University Magna Graecia

Brief Summary:
The goal of this interventional study is to evaluate the increasing in endometrial thickening after the intrauterine infusion of 0,5-1 ml of autologous Platelet-Rich Plasma (PRP) and the implantation rate in women with thin endometrium undergoing Embryo-transfer, in order to propose a novel therapeutic approach for women with an endometrium < 7 mm unresponsive to standard treatments.

Condition or disease Intervention/treatment Phase
Thin Endometrium Endometrial Disorder Endometrial Thickness Not Growing Under Estrogen Stimulation Drug: PRP Device: Tomcat catheter Phase 2

Detailed Description:

In clinical practice, a thin endometrium, unresponsive to conventional therapies, usually results in cycle cancellation and embryo cryopreservation. The evaluation of an adequate endometrial growth is performed using grey-scale ultrasound. The minimal endometrial thickness required for embryo transfer is now considered about 7 mm at the end of natural or medically induced follicular phase, despite some investigators reported different cutoff values, ranging between 7 and 10 mm. Currently, no evidence-based data show the predictive positive value of endometrial thickness on pregnancy rate after Embryo-transfer, but if the endometrial lining is below 7mm the chance of pregnancy is statistically significant reduced.

Thin endometrium is relatively frequent in women with previous trauma of the uterus (cesarean sections, repetitive curettage), patients subjected to antitumoral treatments in childhood (Radiotherapy, Chemotherapy, Surgery), women affected by Asherman's syndrome, chronic infections (endometritis, Pelvic Inflammatory Disease) and inadequate blood flow (stress, malposition of uterus, fibrosis), patients with low estradiol values or excessive use of Clomiphene Citrate.

Several alternative treatments have been proposed over the years to improve the endometrial thickening, then showed themselves to be not considered the answer in many cases: some of them, indeed, require a not damaged endometrium, other act on endometrial blood flow and have no direct proliferative effect on the endometrium. The only factor presumed to have a proliferative effect on endometrium is the Granulocyte-Colony Stimulating Factor (G-CSF) but this hypothesis is not supported by in vitro studies.

Recently, first results from an in vitro study ongoing on the evaluation of Platelet-Rich Plasma (PRP) effect on endometrial cell proliferation have been presented (Aghayanova et al., 2016). The authors demonstrated that PRP increased proliferation not only on cultured fibroblasts, as currently known but also on mesenchymal cells, which are progenitors of different types of cells, including endometrial cells. This evidence supports the hypothesis that PRP stimulates some of the cellular processes involved in endometrial regeneration, that can be relevant to the management of a thin lining.

Autologous Platelet-Rich Plasma is prepared from fresh whole blood which is collected from a peripheral vein and processed to separate platelets from the other blood components. PRP contains activating platelets that stimulate the action of cytokines and growth factors. On the basis of this evidence, local intrauterine infusion of PRP may improve endometrial growth and implantation.

Patients considered to be candidates for a PRP application must undergo a minor hematological evaluation to exclude blood disorders or platelet dysfunction. The study, since it involves the use of a blood component, was approved by Ethical Committee and all participant have to sign an informed written consent before undergoing the procedure.

Any concerns of immunogenic reactions or disease transmission, that exist with homologous blood products, are eliminated because PRP is produced from autologous blood. Preparation of PRP, however, demands many processing steps, thus there is the theoretic possibility of contamination. For these reasons, all samples are subjected to quality and sterility controls within a closed mechanism. No wound infections after PRP applications have been reported. Despite PGF has mitogenic properties, there is no evidence that the growth factors included in PRP promote tumor growth or that they are involved in carcinogenesis.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intrauterine Infusion of Autologous Platelet-Rich Plasma (PRP) in Women With Thin Endometrium Undergoing Embryo-transfer.
Actual Study Start Date : February 27, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : February 27, 2020

Arm Intervention/treatment
Experimental: PRP-infusion
PRP will be obtained from a fresh whole blood collected from a peripheral vein; the blood sample will be centrifuged at 1500g (RCF) for 10 minutes and the repeated reversal of the tube will allow obtaining the PRP at the concentration required. Then 0,5-1ml of PRP will be infused into the uterine cavity through a Tomcat catheter. The endometrial thickening will be evaluated by ultrasonography 24-48h after the instillation and, if the endometrial lining reaches 7mm the Embryo-transfer will be arranged.
Drug: PRP
PRP intrauterine infusion

Device: Tomcat catheter
PRP intrauterine infusion by means Tomcat catheter




Primary Outcome Measures :
  1. Endometrial thickness [ Time Frame: 24-48h after the intrauterine PRP infusion ]
    Endometrial thickness > 7 mm measured by means of transvaginal ultrasound


Secondary Outcome Measures :
  1. Positive pregnancy test rate [ Time Frame: Approximately 3 weeks after treatment ]
    Positive pregnancy test rate after Embryo-transfer

  2. Implantation rate [ Time Frame: Approximately 6 weeks after treatment ]
    defined by number of gestational sacs seen on early pregnancy 6-week ultrasound divided by number of embryos transferred


Other Outcome Measures:
  1. Clinical pregnancy rate [ Time Frame: Approximately 8 weeks after treatment ]
    Defined by the number of fetal poles with heartbeat seen on 6-week ultrasound divided by the number of embryos transferred

  2. Return to spontaneous period [ Time Frame: Approximately 1 to 3 months after treatment ]
    Records of a menstrual flow diary (Menstrual Assessment Chart) for 1-3 months after treatment



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Ages Eligible for Study:   18 Years to 46 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Endometrial thickness < 7 mm under estrogen replacement therapy or repeated implantation failure
  • Age between 18 and 46 years

Exclusion Criteria:

  • Age < 18 and > 46 years
  • Pregnancy
  • Bleeding diathesis
  • Previous uterine surgery (miomectomy, cesarean section, etc...)
  • Platelet count < 105/μL
  • Hemoglobin < 10 g/dL
  • Presence of a tumor in the wound bed or metastatic disease
  • Current diagnosis of cancer
  • Other concomitant active infections

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03067623


Contacts
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Contact: Roberta Venturella, MD +390961883234 venturella@unicz.it
Contact: Sara Pedri, MD +390961883234 sara.pedri89@gmail.com

Locations
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Italy
Pugliese Ciaccio Hospital Recruiting
Catanzaro, Italy, 88100
Contact: Roberta Venturella, MD    +390961883234    venturella@unicz.it   
Sub-Investigator: Adalgisa Brescia, MD         
Sub-Investigator: Andrea Dominijanni, MD         
Sub-Investigator: Sara Pedri, MD         
Sponsors and Collaborators
University Magna Graecia
Investigators
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Principal Investigator: Roberta Venturella, MD Magna Graecia University of Catanzaro

Additional Information:
Publications:
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Responsible Party: Roberta Venturella, Principal Investigator, University Magna Graecia
ClinicalTrials.gov Identifier: NCT03067623     History of Changes
Other Study ID Numbers: PRP-Et
First Posted: March 1, 2017    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Roberta Venturella, University Magna Graecia:
Thin endometrium
Endometrial thickness