P–309 Effectiveness of intrauterine infusion of platelet-rich plasma (PRP) vs. granulocyte colony-stimulating factor (G-CSF) in women with thin endometrium undergoing assisted reproduction
Authors: Pivazyan L , Avetisyan J , Unanyan A , Ishchenko A 
Published: August 2021

Abstract

Study question
To compare the effect of intrauterine infusion of platelet-rich plasma (PRP) and granulocyte colony-stimulating factor (G-CSF) on endometrial thickness, clinical pregnancy rate and live-birth rate.

Summary answer
According to our research, PRP-therapy has more positive results in pregnancy rates. Nevertheless, there is still limited data to answer all questions completely.

What is known already
Thin endometrium is defined as endometrium thickness &lt;7 mm or &lt; 8 mm on the day of human chorionic gonadotropin (HCG) administration, which negatively affects the onset of pregnancy during natural fertilization and in assisted reproduction.
Endometrial thickness may impact pregnancy and live-birth rates in fresh and frozen IVF cycles but, currently, there is minimal evidence to support any specific protocol to significantly improve pregnancy outcomes in patients with thin endometrium. Therefore, we decided to compare effects of two methods: transvaginal intrauterine perfusion of G-CSF for infertile women with thin endometrium in IVF cycles and intrauterine infusion of PRP.

Study design, size, duration
We conducted a systematic review and meta-analysis by PRISMA checklist. PubMed, The Cochrane Library, ClinicalTrials.gov and Google Scholar were searched electronically until 2021 using key words: “G-CSF”, “PRP”, “endometrium”. We included published and unpublished randomized clinical trials (RCT) and non-randomized clinical trials in English which include min.10 patients.

Participants/materials, setting, methods
Participants: female infertile patients of reproductive age with thin endometrium (≤ 7 mm) in embryo transfer cycles. Exclusion criteria: history of any chromosomal or genetic abnormalities and hematological disorders. Outcomes – endometrial thickness, pregnancy and live-birth rates.Risk of bias assessment was held using The Cochrane Handbook and The Cochrane collaboration tools. RoB 2 tool was used for randomized trials and ROBINS-I tool for non-randomized trials. For quantitative synthesis RevMan 5.4 was used to conduct meta-analysis.

Main results and the role of chance
Literature search resulted in 144 potentially relevant publications initially (Google Scholar: 126, PubMed: 1, Clinicaltrials: 14, Cochrane: 3). These publications were checked for titles and abstracts, duplicates were removed and 7 publications were selected. After evaluating the selection criteria, 2 articles were excluded. As a result, 5 articles remained for qualitative and quantitative synthesis, including 2 randomized controlled trials (RCT), 2 retrospective cohort studies, and 1 prospective cohort study. 403 patients participated in selected studies (the PRP group included 205 patients, and the G-CSF group - 198 patients). The primary quantitative analysis (meta-analysis) is aimed at comparison of endometrial thickness in patients receiving PRP therapy and patients receiving G-CSF. Two RCTs were included in this meta-analysis. (RR = 1.07, 95% CI: 0.81 to 1.43, P = 0.63). The heterogeneity for this comparison was 0%. Consequently, both options are equally altered by the thickness of endometrium.
The secondary analysis compared clinical pregnancy rates in patients receiving PRP therapy and G-CSF. 4 studies were eligible for this synthesis. (RR = 1.36, 95% Cl: 1.06 to 1.76, P = 0.02). The heterogeneity for this comparison was 55%. PRP was significantly more effective.

Limitations, reasons for caution
Firstly, only 5 publications were found for the entire time. There are not enough well-conducted studies for more accurate analysis. Secondly, according to risk of bias assessment most of included studies had moderate concerns. Finally, there is no sufficient data to judge about live-birth rates after both types of treatment.
Wider implications of the findings: Thin endometrium negatively affects the onset of pregnancy in assisted reproduction.Based on our meta-analysis, PRP therapy has a considerable effect on pregnancy rates in patients with thin endometrium in comparison with G-CSF.Currently, there is minimal evidence to support any specific protocol for improving IVF outcomes in women with thin endometrium.

Trial registration number
PROSPERO 2020 CRD42020222075