Decidualization score identifies an endometrial dysregulation in samples from women with recurrent pregnancy losses and unexplained infertility

Abstract

Objective: To study decidualization-associated endometrial factors. Design: Retrospective cohort study to compare endometrial gene expression patterns in women experiencing reproductive failure including recurrent pregnancy loss or unexplained infertility versus fertile controls. Setting: University Reproductive Medicine Center. Patient(s): Women experiencing recurrent reproductive failure including recurrent pregnancy loss or unexplained infertility (n ¼ 42) and fertile controls (n ¼ 18). Intervention(s): Endometrial biopsy samples were analyzed with targeted ribonucleic acid sequencing via next-generation sequencing. Main Outcome Measure(s): The primary end point measurements were the expression of genes important for endometrial transformation during decidualization measured singly and in a combined/cumulative score approach. The secondary end point measurements were receiver operating curve analysis and comparisons between the specific biomarkers. Result(s): The comparison revealed differential expression of factors associated with decidualization, tissue homeostasis, and immune regulation: FOXO1, GZMB, IL15, SCNN1A, SGK1, and SLC2A1. A combined evaluation of these 6 signature factors was designated as a decidualization score in which the maximal score was ''6'' and the minimal was ''0''. Among controls, 89% of the samples had a score R5 and 11% had a score of ''4''. A total of 76% of samples in the patient group had scores %4 and 19% had the lowest score of ''0''. A decidualization score <4 provided evidence of abnormality in the decidualization process with a sensitivity of 76% (95% CI 61%-88%) and specificity of 89% (95% CI 65%-99%). Conclusion(s): Decidualization scoring can determine whether the endometrial molecular profile is implantation-friendly. Further validation of this testing approach is necessary to determine a particular patient population in whom it could be used for selecting patients that require therapeutic actions to improve endometrial conditions prior to the in vitro fertilization procedure (Fertil Steril Rep Ò 2021;2:95-103. Ó2020 by American Society for Reproductive Medicine.

Stromal cell decidualization and embryo implantation: a vulnerable step leading to successful pregnancy

“…Maternal endometrial dysfunction is an important contributor to RPL development. Using the decidualization score, which combines the expression of genes associated with decidualization, tissue remodeling, and immune responses, Dambaeva et al [133] showed that RPL and unexplained infertility are related to endometrial dysregulation. The decrease in N-myc downstream regulated 1 and brain and muscle aryl hydrocarbon receptor nuclear translocator-like genes in ESCs results in impaired decidualization and pregnancy loss or miscarriage [134,135] .…”

Evaluation of endometrial receptivity and implantation failure

“…The primary secretory products of decidual cells (IGFB1 and Prolactin) as well as WNT4, itself, require FOXO1 for expression [20]. Finally, a recent paper [21] presented preliminary evidence for an endometrial function scoring system based on mRNA expression levels of six genes, which include SGK1, FOXO1, and IL-15.…”

ID3 mediates BMP2-induced downregulation of ICAM1 expression in human endometiral stromal cells and decidual cells

“…In recent decades, extensive research has been carried out to elucidate the biomolecular mechanisms that promote the acceptance of the embryo by the endometrium and the specific molecules and cellular pathways involved in endometrial receptivity. A number of studies have shown that various factors are dysregulated in the endometrium of women with uRPL (Comba et al, 2015;Dambaeva et al, 2021;Heidari et al, 2021;Zhu et al, 2022), including intercellular adhesion molecule 1 (ICAM1). ICAM1 is a single-chain, 90 kDa inducible cell-surface glycoprotein and a member of the immunoglobulin superfamily (Rothlein et al, 1991).…”