P-366 Unraveling the whole transcriptome profiles of receptive phase endometrium in infertile women

Abstract

Abstract Study question Are there differential transcriptomic profiles of the receptive phase endometria in infertile women with different infertility diagnoses? Summary answer Endometrium-related pathologies such as endometriosis and RIF seemed to share similar endometrial molecular profiles in mid-secretory phase,while samples from unexplained infertility were similar to controls. What is known already Successful embryo implantation is orchestrated by the combination of a viable blastocyst, a receptive endometrium and a perfectly synchronized molecular dialogue between them. Endometrium-associated pathologies such as endometriosis and recurrent implantation failure (RIF) are suggested to hamper endometrial receptivity, but the molecular mechanisms affected in these and other infertility diagnoses such as unexplained infertility need further investigation. Previous transcriptome studies of the human endometrium have analysed different infertility diagnoses separately, but whether and to what extent receptive-phase endometrial transcriptome profiles vary between distinct infertility diagnoses is underexplored. Study design, size, duration A prospective, cross-sectional study was performed at the Reproductive Unit at the University Hospital between March 2019 and April 2021. Forty-five well-characterized infertile women (age 34.7±3.8 years, BMI 24.5±kg/m2) were recruited before starting any infertility treatment. Four groups according to different infertility diagnoses were established: endometriosis (n = 12), RIF (n = 14), unexplained infertility (n = 10), and male factor infertility as control group (n = 9). Participants/materials, setting, methods Endometrial biopsies were collected using Pipelle curette during mid-secretory phase (LH + 7) of the natural cycle. Total RNA was extracted and sequenced using Illumina NovaSeq 6000 technology. Raw sequencing data was quality assessed, pre-processed and quantified, and differential expression and enrichment analyses were performed using R software. Main results and the role of chance Differential expression analysis revealed 743, 587 and 140 differentially expressed genes (DEGs) in endometriosis, RIF and unexplained infertility, respectively, when compared to control women of the male factor infertility group. Among these, 31 genes exhibited consistent differential expression between all infertility groups. Regarding functional enrichment analyses, the detected DEGs were mainly related to immune response and inflammatory processes, supporting the involvement of these pathways in the impairment of endometrial receptivity. Interestingly, the comparison between different study groups showed similar transcriptome profiles in endometrium-associated pathologies such as endometriosis and RIF, while women with unexplained infertility had similar molecular profiles with the control group of male factor infertility. These study results indicate common molecular pathways in endometrial receptivity between infertile women with endometriosis and RIF, and between unexplained infertility and control male factor infertility patients. Limitations, reasons for caution Further research with bigger sample size is required to confirm these findings. Wider implications of the findings We identified transcriptome profiles associated with infertility diagnoses. Further, women with unexplained infertility tended to have similar molecular profiles with control women, meaning that other factors than endometrial receptivity issues could lead to their infertility. Our study helps to understand the molecular mechanisms underlying female infertility in different infertility diagnoses. Trial registration number not applicable