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Background: Women with uterine adenomyosis seeking assisted reproduction have been associated with compromised endometrial receptivity to embryo implantation. To understand the mechanisms involved in this process, we aimed to compare endometrial transcriptome profiles during the window of implantation (WOI) between women with and without adenomyosis., Methods: We obtained endometrial biopsies LH-timed to the WOI from women with sonographic features of adenomyosis (n=10) and controls (n=10). Isolated RNA samples were subjected to RNA sequencing (RNA-seq) by the Illumina NovaSeq 6000 platform and endometrial receptivity classification with a molecular tool for menstrual cycle phase dating (beREADY®, CCHT). The program language R and Bioconductor packages were applied to analyse RNA-seq data in the setting of the result of accurate endometrial dating. To suggest robust candidate pathways, the identified differentially expressed genes (DEGs) associated with the adenomyosis group in the receptive phase were further integrated with 151, 173 and 42 extracted genes from published studies that were related to endometrial receptivity in healthy uterus, endometriosis and adenomyosis, respectively. Enrichment analyses were performed using Cytoscape ClueGO and CluePedia apps., Results: Out of 20 endometrial samples, 2 were dated to the early receptive phase, 13 to the receptive phase and 5 to the late receptive phase. Comparison of the transcriptomics data from all 20 samples provided 909 DEGs (p<0.05; nonsignificant after adjusted p value) in the adenomyosis group but only 4 enriched pathways (Bonferroni p value < 0.05). The analysis of 13 samples only dated to the receptive phase provided suggestive 382 DEGs (p<0.05; nonsignificant after adjusted p value) in the adenomyosis group, leading to 33 enriched pathways (Bonferroni p value < 0.05). These included pathways were already associated with endometrial biology, such as "Expression of interferon (IFN)-induced genes" and "Response to IFN-alpha". Data integration revealed pathways indicating a unique effect of adenomyosis on endometrial molecular organization (e.g., "Expression of IFN-induced genes") and its interference with endometrial receptivity establishment (e.g., "Extracellular matrix organization" and "Tumour necrosis factor production")., Conclusions: Accurate endometrial dating and RNA-seq analysis resulted in the identification of altered response to IFN signalling as the most promising candidate of impaired uterine receptivity in adenomyosis., (© 2021. The Author(s).)

Background: Adenomyosis is a gynaecological condition with limited evidence of negative impact to endometrial receptivity. It is commonly associated with endometriosis, which has been shown to alter endometrial expression patterns. Therefore, the candidate genes identified in endometriosis could serve as a source to study endometrial function in adenomyosis., Methods: Transcripts/proteins associated with endometrial receptivity in women with adenomyosis or endometriosis and healthy women were obtained from publications and their nomenclature was adopted according to the HUGO Gene Nomenclature Committee (HGNC). Retrieved genes were analysed for enriched pathways using Cytoscape/Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Reactome tools to prioritise candidates for endometrial receptivity. These were used for validation on women with ( n = 9) and without ( n = 13) adenomyosis., Results: Functional enrichment analysis of 173, 42 and 151 genes associated with endometriosis, adenomyosis and healthy women, respectively, revealed signalling by interleukins and interleukin-4 and interleukin-13 signalling pathways, from which annotated LIF , JUNB , IL6 , FOS , IL10 and SOCS3 were prioritised. Selected genes showed downregulated expression levels in adenomyosis compared to the control group, but without statistical significance., Conclusion: This is the first integrative study providing putative candidate genes and pathways characterising endometrial receptivity in women with adenomyosis in comparison to healthy women and women with endometriosis.

Purpose: The purpose of this study was to find out the most important prognostic factors for achieving a pregnancy after in vitro fertilization (IVF) in women with history of repeated unsuccessful IVF attempts., Methods: We analyzed factors affecting pregnancy rate in a retrospective study including 429 IVF/ICSI cycles performed in women younger than 40 years with at least three previous consecutive failed IVF/ICSI attempts., Results: Clinical pregnancy was observed in 140/429 (32.6%) cycles. Clinical pregnancy rate (CPR) was significantly higher in cycles with LEI compared to cycles without LEI before embryo transfer (44.4 vs 26.54%, p = 0.007). The CPR was also higher in cycles with day 5 blastocyst- compared with day 3 cleavage-stage embryo transfers (45.51 vs 26.54%, p < 0.001). In multivariate logistic regression model, only transfer of at least one good quality embryo (OR = 4.32, 95% CI 2.41-7.73), local endometrial injury (OR = 1.73, 95% CI 1.02-2.92), and transfer on day 5 (OR = 3.02, 95% CI 1.53-5.94) remained important independent prognostic factors for clinical pregnancy., Conclusions: These results suggest that hysteroscopy with local injury to the endometrium prior to ovarian stimulation for IVF/ICSI can improve implantation and pregnancy rates in women experiencing recurrent IVF failure. However, large studies are needed to confirm these findings.