Molecular insights into p53-driven hormonal dysregulation and ART failure

Abstract Objective Infertility is an increasing global concern, with Assisted Reproductive Technology (ART) playing a crucial role in improving reproductive outcomes. Emerging evidence highlights the significance of the tumor suppressor protein p53 in fertility, implantation, and ART success. Prolactin, a key reproductive hormone, also plays a critical role in fertility, with its imbalance contributing to menstrual irregularities, ovulatory dysfunction, and impaired spermatogenesis. Although p53 and prolactin have individually been associated with reproductive outcomes, their combined clinical relevance in ART failure remains inadequately characterized. The potential interaction between p53 expression and prolactin levels may reflect hormonal dysregulation associated with ART outcomes rather than a direct causal mechanism. Therefore, this study aims to investigate the associative relationship between p53 and prolactin to identify potential predictive biomarkers for ART success or failure. Methodology This case-control study included 600 adults from hospitals across Kerala, with 300 infertility cases who underwent ART treatment and 300 fertile controls matched by age. Blood samples were collected for hormonal and genetic analysis, including prolactin measurement via ELISA and p53 gene expression assessment using Real-Time PCR. Statistical analysis, including t-tests and ROC curve analysis, were conducted using Stata 17.0 and RStudio, with a significance threshold of p < 0.05. Ethics approval was obtained, and all participants provided informed consent. Result Comparative analysis revealed significantly elevated prolactin levels and p53 gene expression in cases ( p < 0.001), with prolactin showing a more substantial effect in females. ROC analysis confirmed prolactin as a strong discriminatory marker of infertility, achieving an AUC of 0.828 in males and 0.918 in females. Scatter plot analysis demonstrated a positive but weak association between prolactin levels and p53 expression, with considerable inter-individual variability and no evidence of causality. Conclusion This study demonstrates that elevated prolactin and increased p53 expression are significantly associated with ART failure, with prolactin emerging as a strong predictive biomarker, particularly in females. Given the observational nature of the study, causality cannot be inferred, and the findings should be interpreted as hypothesis-generating. Although causality cannot be inferred from expression-based analyses alone, these findings highlight a clinically relevant hormonal–molecular signature that warrants further functional investigation.