Autologous Platelet-Rich Plasma (PRP) and Endometrial Thickness

NCT ID: NCT03067623

Last Updated: 2019-05-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-27
• Study Completion Date: 2020-02-27

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.

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.

Conditions

Thin Endometrium; Endometrial Disorder; Endometrial Thickness Not Growing Under Estrogen Stimulation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

PRP

Intervention Type: DRUG

PRP intrauterine infusion

Tomcat catheter

Intervention Type: DEVICE

PRP intrauterine infusion by means Tomcat catheter

Interventions

PRP

PRP intrauterine infusion

Intervention Type: DRUG

Tomcat catheter

PRP intrauterine infusion by means Tomcat catheter

Intervention Type: DEVICE

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 46 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Magna Graecia

OTHER

Sponsor Role: lead

Responsible Party

Roberta Venturella

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Roberta Venturella, MD

Role: PRINCIPAL_INVESTIGATOR

Magna Graecia University of Catanzaro

Locations

Pugliese Ciaccio Hospital

Catanzaro, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Roberta Venturella, MD

Role: CONTACT

venturella@unicz.it

+390961883234

Sara Pedri, MD

Role: CONTACT

sara.pedri89@gmail.com

+390961883234

Facility Contacts

Roberta Venturella, MD

Role: primary

venturella@unicz.it

+390961883234

References

Chang Y, Li J, Chen Y, Wei L, Yang X, Shi Y, Liang X. Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med. 2015 Jan 15;8(1):1286-90. eCollection 2015.

Reference Type: BACKGROUND

PMID: 25785127 (View on PubMed)

Nazari L, Salehpour S, Hoseini S, Zadehmodarres S, Ajori L. Effects of autologous platelet-rich plasma on implantation and pregnancy in repeated implantation failure: A pilot study. Int J Reprod Biomed. 2016 Oct;14(10):625-628.

Reference Type: BACKGROUND

PMID: 27921085 (View on PubMed)

L. Aghajanova, S. Houshdaran, S. Balayan, J. Irwin, H. Huddleston, L. Giudice. Platelets for endometrial regeneration: a novel approach. Fertil Steril. Volume 106, Issue 3, Supplement, Page e82

Reference Type: BACKGROUND

Related Links

https://clinicaltrials.gov/ct2/show/record/NCT02825849?term=prp+endometrium&rank=2

Ongoing Trial

Other Identifiers

PRP-Et

Identifier Type: -

Identifier Source: org_study_id