P-361 Granulocyte colony-stimulating factor and platelet-rich plasma improve pregnancy outcomes in patients with thin endometrium and recurrent implantation failure (RIF) in frozen embryo transfer cycles (FET)
Authors: Dzhincharadze L , Abubakirov A , Martazanova B , Korolkova A , Mikhaylova N , Fedorova T , Mishieva N 
Published: June 2022

Abstract

Study question
Does the use of granulocyte colony-stimulating factor (G-CSF) and platelet-rich (PRP) plasma improve endometrial thickness and pregnancy outcome in patients with thin endometrium and RIF?

Summary answer
The use of G-CSF and PRP improve the endometrial thickness and pregnancy outcome in patients with thin endometrium and RIF undergoing artificial FET cycles

What is known already
Thin endometrium is a negative prognostic factor for achieving pregnancy, which occurs in 2.4% of assisted reproductive technology cycles. According to previous studies use of G-CSF and PRP are perspective methods for these patients’ management. G-CSF is a polypeptide that belongs to the colony-stimulating factor glycoprotein group. PRP is derived from patient’s own blood and contains platelets’ growth factors that promote reparation in tissues. However, there is limited data about IVF treatment success after G-CSF or PRP perfusion in patients with thin endometrium and RIF, also there are no studies comparing these two protocols.

Study design, size, duration
This prospective observational study included 163 patients. All the patients underwent artificial frozen-thawed embryo transfer cycles. Group 1 (n = 43), the control group, did not get additional therapy. Group 2 (n = 46) received intrauterine G-CSF (300 mcg) perfusion on 5-6 and 8-9 days of cycle. Group 3 (n = 74) received intrauterine PRP (5-7 ml) perfusion on 8-9, 10-11 and 12-13 days of cycle. The study was carried out between December 2017 and December 2019.

Participants/materials, setting, methods
Inclusion criteria: age 20-42 years; BMI 18-30 kg/m2; endometrial thickness on embryo transfer (ET) day ≤ 7mm in previous cycles; previous non-effective ET cycles; good quality embryos (Gardner and Schoolcraft classification). Exclusion criteria: uterine fibroids ≥4 cm; deep endometriosis; Asherman syndrome; allergic reaction to G-CSF. PRP was prepared by the double centrifugation technique (Beckman, USA). From 400 ± 50 ml of whole blood was made 40 ± 5 ml PRP with 0,6-0,7 x 1011 platelets.

Main results and the role of chance
Endometrial thickness on ET day in Group 1 was 7,0±1,1 mm, in Group 2 – 7,9±1,8 mm, in Group 3 – 8,0±1,3 mm. The difference was statistically significant between Group 1 and 2 – p = 0,003 (MD-0,96; 95% CI: 0,33; 1.59), between Group 1 and 3 – p = &lt;0,001 (MD-1,0; 95% CI: 0,53; 1,47). No statistically significant difference was between Group 2 and 3 – p = 0,790 (MD-0,004; 95% CI: -0,53; 0,61). FET cycle cancelled due to thin endometrium occurred in 26 (60,5%), 18 (39,1%) and 13 (17,6%) patients in Groups 1,2 and 3 respectively. Pregnancy rate was statistically significant different between Group 1 and 2 – p = 0,005 (5,9% (1/17) vs. 46,4% (13/28), OR-0,07; 95%CI: 0,01; 0,62), between Group 1 and 3 – p = 0,007 (5,9%(1/17) vs. 41,0%(25/61), OR-0,09; 95%CI: 0,01; 0,72). No statistically significant difference was between Group 2 and 3 in pregnancy rate – p = 0,630 (46,4% (13/28) vs. 41,0% (25/61)). There was statistically significant difference in livebirth rate between Group 1 and 2 – p = 0,003 (0 (0/17) vs. 39,3% (11/28), between Group 1 and 3 – p = 0,014 (0 (0/17) vs. 27,9% (17/61). No statistically significant difference was in livebirth rate between Group 2 and 3 – p = 0,282 (39,3% (11/28) vs. 27,9% (17/61)).

Limitations, reasons for caution
Our study was carried out in a relatively small subset of patients; also in our study we investigated only FET cycles. There should be larger trials in future, including fresh embryo transfer cycles.

Wider implications of the findings
This study opens new possibilities in management of patients with thin endometrium.

Trial registration number
N/A