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 = 42) and fertile controls (n = 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 ≥5 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

Keywords

• Endometrium
• gene expression
• recurrent pregnancy loss
• infertility
• decidualization