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Clinical Trials/NCT03067623
NCT03067623UnknownPhase 2

Intrauterine Infusion of Autologous Platelet-Rich Plasma (PRP) in Women With Thin Endometrium Undergoing Embryo-transfer.

University Magna Graecia1 site in 1 country200 target enrollmentStarted: February 27, 2017Last updated:
Conditions
Interventions
Drugs

Trial Snapshot

Phase
Phase 2
Sponsor
Enrollment
200
Locations
1
Primary Endpoint
Endometrial thickness

Study Overview

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.

Study Design

Study Type
Interventional
Allocation
Na
Intervention Model
Single Group
Primary Purpose
Treatment
Masking
None

Eligibility Criteria

Ages
18 Years to 46 Years (Adult)
Sex
Female
Accepts Healthy Volunteers
No

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

Arms & Interventions

PRP-infusion

Experimental

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.

Intervention: PRP (Drug)

PRP-infusion

Experimental

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.

Intervention: Tomcat catheter (Device)

Outcomes

Primary Outcomes

Endometrial thickness

Time Frame: 24-48h after the intrauterine PRP infusion

Endometrial thickness \> 7 mm measured by means of transvaginal ultrasound

Secondary Outcomes

  • Positive pregnancy test rate(Approximately 3 weeks after treatment)
  • Implantation rate(Approximately 6 weeks after treatment)

Investigators

Sponsor
University Magna Graecia
Sponsor Class
Other
Responsible Party
Principal Investigator
Principal Investigator

Roberta Venturella

Principal Investigator

University Magna Graecia

Study Sites (1)

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