HOXA10 and HOXA11 Methylation: Epigenetic Barriers to Endometrial Receptivity in ART

The global prevalence of infertility has reached critical levels, making it one of the most pressing issues in modern society. Assisted reproductive technologies (ARTs), particularly in vitro fertilization (IVF), are the primary treatment methods for infertility. However, even under optimal conditions, the pregnancy rate per IVF cycle does not exceed 40%, while the live birth rate remains around 30%. A key unresolved challenge in ART is impaired endometrial receptivity (ER), which significantly contributes to repeated implantation failure (RIF). Advances in molecular and genetic diagnostics have revealed that gynecological conditions associated with infertility, such as chronic endometritis, uterine fibroids, polycystic ovary syndrome (PCOS), and tuboperitoneal factor infertility, are often linked to epigenetic alterations. Specifically, abnormal hypermethylation of the promoter regions of the HOXA10 and HOXA11 genes has been observed in women of reproductive age with these conditions. Such epigenetic dysregulation negatively impacts ER and is associated with infertility. The methylation status of HOXA10 and HOXA11 may serve as a potential diagnostic marker for evaluating and treating infertility. These markers can be assessed using available molecular genetic techniques, including real-time PCR. A promising therapeutic approach to improve ER involves the use of epigallocatechin-3-gallate and indole-3-carbinol, which have been shown to demethylate and restore the expression of HOXA10 and HOXA11. Epigenetic regulation holds significant potential for enhancing the effectiveness of ART programs, offering new avenues for addressing infertility and improving reproductive outcomes. This review consolidates the current body of knowledge regarding the epigenetic regulation of endometrial receptivity. It outlines fundamental scientific data on epigenetic mechanisms and discusses contemporary diagnostic and pharmacological intervention strategies.