P-383 Endometrial scratching: A strategy to stimulate the angiogenesis aspect of implantation in unexplained, repeated implantation failure
Authors: Aghajanpour S , Mehraeen F , Amjadi  , Zandieh  , Hosseini E , Ghaffari F , Yahyaei A , Aflatoonian K , Bakhtiyari M , Aflatoonian R 
Published: June 2022

Abstract

Study question
Does endometrial scratching serve as an angiogenic stimulator during implantation in unexplained, repeated implantation failure (uRIF) patients?

Summary answer
Endometrial scratching can reimburse and regulate genes involved in both endometrial angiogenesis and receptivity.

What is known already
The vascular endothelial growth factor (VEGF), as an angiogenic factor, is well-known for its function in a variety of physiological and pathological aspects of female reproduction. Following the embryo transfer in the In-Vitro Fertilization cycles, the most challenging clinical obstacle to overcome is RIF. Endometrial scratching is a technique considered as an option for enhancing the embryo implantation of uRIF patients by modulating the different cellular and molecular components regulating endometrial receptivity before and during implantation.

Study design, size, duration
Twenty uRIF patients were enrolled based on a randomized controlled trial (RCT) to study the expression of genes involved in endometrial angiogenesis and receptivity functions (VEGFR1, VEGFR2, COL18A1, E-cadherin, FGF1) following ES. Ten uRIF patients were randomly assigned to the intervention group (twice endometrial sampling in the follicular and luteal phases) and ten in the control group (only luteal phase sampling) prior to the ovarian stimulation cycle.

Participants/materials, setting, methods
Women who failed to conceive following three or more IVF/ICSI cycles, high-quality embryo transfer, and at least one blastocyst embryo transfer cycle met the inclusion criteria. Post-biopsy endometrial samples were divided evenly. One component was placed in 10% formalin for histology dating and another in RNALater for genomic analysis and preserved at -80 °C for RNA extraction.

Main results and the role of chance
The expression levels of VEGFR1 and VEGFR2 (both as the receptors of VEGF) were significantly increased after ES (P &lt;0.05).
The mRNA expression level of COL18A1 was significantly decreased after ES. COL18A1 is an inhibitor of VEGF which can impede VEGF-mediated signaling and endothelial cell proliferation, via blocking of its receptor specifically VEGFR2.
The E-cadherin expression level was significantly decreased (P &lt;0.05) in the endometrium of the intervention group after scratching. E-cadherin is a cell-cell adhesion molecule that has a pivotal role in maintaining normal epithelial architecture, establishing cell polarity, glandular differentiation, and morphogenesis.
Data showed that Fibroblast Growth Factor1 (FGF1) expression level was significantly increased in the intervention group (P &lt;0.05). FGF1 promotes the formation of blood vessels which improves endometrial trophoblastic interaction and affects embryo implantation.

Limitations, reasons for caution
To further understand the function of these changes, it is preferable to compare the data with endometrium from a fertile group, which is ongoing.

Wider implications of the findings
On the timeline of embryo implantation, angiogenic factors (e.g., VEGFR1 and VEGFR2), their inhibitors (e.g., E-cadherin and COL18A1), and activators (e.g., FGF1) work together to establish a dynamic environment responsible for endometrial receptivity, which has been compromised in the endometrium of RIF patients.ES can reimburse and regulate these angiogenesis processes.

Trial registration number
IRCT20210316050723N1