P-414 Evaluation of small non-coding RNAs in uterine fluid in the diagnosis of endometrial receptivity in assisted reproductive technology programs
Authors: Gokhberg Y , Kalinina E , Timofeeva A 
Published: July 2024

Abstract

Study question
To analyze endometrial receptivity in patients undergoing frozen-thawed embryo transfer (FET) based on the expression of small non-coding RNAs (sncRNAs): microRNAs and piwiRNAs.

Summary answer
According to our studies, the expression of sncRNAs in uterine aspirate may become an additional non-invasive and effective way to determine endometrial receptivity.

What is known already
Today, infertility remains an important medical and social problem. According to statistics, the effectiveness of ART programs remains at the level of 30-40%. Violation of the implantation mechanism is associated with a shift in the “implantation window” period and endometrial receptivity. Therefore, the search for an ideal marker of endometrial receptivity is a priority. Studying the expression of sncRNAs in endometrial secretions or uterine aspirate may become a potential marker of endometrial receptivity.

Study design, size, duration
The study included 102 infertile couples with women aged from 23 to 40 years. The patients were divided into two groups depending on the preparation of the endometrium for the FET: group 1 - 42 patients with natural cycle (NC); group 2 - 60 patients with hormone replacement therapy (HRT). SncRNAs were assessed in uterine aspiration on the day of FET.

Participants/materials, setting, methods
Uterine fluid was carried out in a volume of 5 to 50 μl with noninvasive technique. Next, the material was sent to the laboratory of applied transcriptomics for identification of sncRNAs. Quantitative assessment of sncRNAs in the endometrial secretion on the day of FET was carried out by deep sequencing on the NextSeq 500/550 platform (Illumina).

Main results and the role of chance
Logistic regression models were constructed for predicting pregnancy and endometrial receptivity based on the expression profiles of microRNAs and piwiRNAs in uterine aspirate, which are with 95% sensitivity and 74% specificity in the case of a combination of miR-34c-5p, miR-363–3p, miR-1180–3p, miR-361–3p, miR-183–5p (AUC = 0.91, p &lt; 0.001) or with 74% sensitivity and 87% specificity in the case of a combination of molecules piR_004152, piR_020541, piR_001318, piR_014923, piR_017716 (AUC = 0.81, p &lt; 0.001) determine the readiness of the endometrium for embryo implantation in the FET.
In the NC and HRT groups, statistically significant differences were established between patients who became pregnant and patients with a negative result of the ART program in terms of baseline progesterone levels (p &lt; 0.001). In the HRT group, positive correlations were revealed between endometrial thickness on the day of embryo transfer and the baseline level of progesterone (p = 0.04, r = 0.28).

Limitations, reasons for caution
The study was limited in sample size of patients and requires further randomized studies.

Wider implications of the findings
For the first time, a test system has been developed for assessing endometrial receptivity based on the expression of sncRNAs in patients both in the NC and in the HRT during the FET. It was found that increased initial progesterone levels correlate with positive outcomes of ART programs.

Trial registration number
not applicable