Endometrial Steroid Receptor Dysregulation and Its Association with Vitamin D, AMH, and Inflammation in Recurrent Implantation Failure: A Case-Control Study.

Abstract

Background: Defects in endometrial receptivity are significant factors in infertility and recurrent implantation failure (RIF) during in vitro fertilization (IVF). This study aimed to evaluate the expression levels of steroid hormone receptors and circulating biomarkers in women with RIF compared to fertile controls.

Materials and methods: This case-control study was conducted in Tehran from June 2021 to December 2023, involving 50 fertile women as controls and 50 women with unexplained RIF referred to the RIF Medical Center at Arash Hospital. Blood samples and endometrial biopsies were collected at the day of the LH surge was LH 0. The expression levels of estrogen receptors (ESR-α and ESR-β) and progesterone receptor B (PGR-B) in endometrial tissue were assessed using real-time polymerase chain reaction (RT-PCR). Serum levels of estrogen were measured by enzyme-linked immunosorbent assay (ELISA).

Results: Women with RIF exhibited significantly higher ESR-α expression and lower ESR-β and PGR-B expression compared to fertile women (P<0.001). A positive correlation was found between ESR-α gene expression and hs-CRP levels, while ESR-β and PGR-B were associated with AMH concentrations. RIF patients showed lower serum levels of AMH and Vit-D3, but elevated hs-CRP. Fertile women demonstrated a positive association between PGR-B expression and Vit-D3 levels. The ROC curve analysis revealed high discrimination power for the expression of ESR-α (AUC 1.00), ESR-β (0.988), and PGR-B (0.898).

Conclusion: The study links endometrial PGR-B expression and vitamin D3 levels to decidualization and inflammation regulation. It suggests that infertility in women with RIF may stem from elevated ESR-α, increased inflammation, and reduced ESR-β and PGR-B expression. Further research is needed on PGR-B, VDR gene expression, and fertility biomarkers. ROC analysis indicates that endometrial steroid receptor expression, AMH, and vitamin D3 levels could aid in diagnosing RIF.