Clinical trial NCT03067623: Autologous Platelet-Rich Plasma (PRP) and Endometrial Thickness
Official title: Intrauterine Infusion of Autologous Platelet-Rich Plasma (PRP) in Women With Thin Endometrium Undergoing Embryo-transfer.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Thin Endometrium
Endometrial Disorder
Endometrial Thickness Not Growing Under Estrogen Stimulation
Keywords: Thin endometrium
Endometrial thickness
Lead sponsor: University Magna Graecia
Sponsor class: OTHER
First posted: 2017-03-01
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 46
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Endometrial thickness
timeFrame: 24-48h after the intrauterine PRP infusion
Secondary outcomes:
measure: Positive pregnancy test rate
timeFrame: Approximately 3 weeks after treatment
measure: Implantation rate
timeFrame: Approximately 6 weeks after treatment
Other outcomes:
measure: Clinical pregnancy rate
timeFrame: Approximately 8 weeks after treatment
measure: Return to spontaneous period
timeFrame: Approximately 1 to 3 months after treatment
Locations:
city: Catanzaro
country: Italy
facility: Pugliese Ciaccio Hospital
Study officials:
affiliation: Magna Graecia University of Catanzaro
name: Roberta Venturella, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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