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

Svetlana Dambaeva; Mahmood Bilal; Sylvia Schneiderman; Alfredo Germain; Emilio Fernandez; Joanne Kwak-Kim; Kenneth Beaman; Carolyn Coulam

doi:10.1016/j.xfre.2020.12.004

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

F S Rep. 2020 Dec 29;2(1):95-103. doi: 10.1016/j.xfre.2020.12.004. eCollection 2021 Mar.

Authors

Svetlana Dambaeva¹, Mahmood Bilal¹, Sylvia Schneiderman¹, Alfredo Germain², Emilio Fernandez², Joanne Kwak-Kim³, Kenneth Beaman¹, Carolyn Coulam¹

Affiliations

¹ Clinical Immunology Laboratory, the Center for Cancer Cell Biology, Immunology and Infection, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois.
² Reproductive Medicine, Clinica las Condes, Santiago, Chile.
³ Reproductive Medicine and Immunology, Obstetrics and Gynecology, Clinical Sciences Department, Chicago Medical School, Rosalind Franklin University of Medicine and Science, Vernon Hills, Illinois.

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.

Patients: Women experiencing recurrent reproductive failure including recurrent pregnancy loss or unexplained infertility (n = 42) and fertile controls (n = 18).

Interventions: Endometrial biopsy samples were analyzed with targeted ribonucleic acid sequencing via next-generation sequencing.

Main outcome measures: 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.

Results: 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%).

Conclusions: 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; decidualization; gene expression; infertility; recurrent pregnancy loss.