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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03067623
Other study ID # PRP-Et
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date February 27, 2017
Est. completion date February 27, 2020

Study information

Verified date May 2019
Source University Magna Graecia
Contact Roberta Venturella, MD
Phone +390961883234
Email venturella@unicz.it
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 200
Est. completion date February 27, 2020
Est. primary completion date December 31, 2019
Accepts healthy volunteers No
Gender Female
Age group 18 Years to 46 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
PRP
PRP intrauterine infusion
Device:
Tomcat catheter
PRP intrauterine infusion by means Tomcat catheter

Locations

Country Name City State
Italy Pugliese Ciaccio Hospital Catanzaro

Sponsors (1)

Lead Sponsor Collaborator
University Magna Graecia

Country where clinical trial is conducted

Italy, 

References & Publications (3)

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. — View Citation

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

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 (Yazd). 2016 Oct;14(10):625-628. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Other Clinical pregnancy rate Defined by the number of fetal poles with heartbeat seen on 6-week ultrasound divided by the number of embryos transferred Approximately 8 weeks after treatment
Other Return to spontaneous period Records of a menstrual flow diary (Menstrual Assessment Chart) for 1-3 months after treatment Approximately 1 to 3 months after treatment
Primary Endometrial thickness Endometrial thickness > 7 mm measured by means of transvaginal ultrasound 24-48h after the intrauterine PRP infusion
Secondary Positive pregnancy test rate Positive pregnancy test rate after Embryo-transfer Approximately 3 weeks after treatment
Secondary Implantation rate defined by number of gestational sacs seen on early pregnancy 6-week ultrasound divided by number of embryos transferred Approximately 6 weeks after treatment
See also
  Status Clinical Trial Phase
Completed NCT03724617 - Clinical Study of Umbilical Cord Mesenchymal Stem Cells Combined With Collagen Scaffold in the Treatment of Thin Endometrium N/A
Not yet recruiting NCT04100655 - The Effect of the GM-CSF Gel on the Endometrial Thickness in Infertile Women With Thin Endometrium N/A
Recruiting NCT04292886 - Thin Endometrium Undergoing Frozen-thawed Embryo Transfer N/A
Completed NCT05455151 - Hysteroscopic Injections of Autologous Endometrial Cells and Platelet-rich Plasma in Patients With Thin Endometrium Phase 1
Recruiting NCT06379659 - Effectiveness of Intrauterine Growth Hormone Administration as an add-on Therapy to Conventional Hormone Therapy Compared to Placebo in Patients With Thin Endometrium Undergoing Frozen Thawed Embryo Transfer Phase 1/Phase 2
Recruiting NCT06234540 - a-PRP Intrauterine Instillation in Women With Thin Endometrium N/A

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