Abstract
BACKGROUND: Apoptosis is a continuous process throughout follicular development and plays a critical role in normal ovarian physiology. Although the key apoptotic molecule-encoding genes have been well characterized, their associations with ovarian reserve and pregnancy outcomes remain controversial. Such inconsistency largely arises from confounding effects of uncontrolled variables and methodological limitations in the quantification of apoptosis. To address this knowledge gap, the present study systematically evaluated the correlation between granulosa cell apoptosis and ovarian reserve, as well as its subsequent impact on ovarian stimulation outcomes, using specific apoptotic marker gene expression analysis. METHODS: A prospective cohort study was conducted involving 75 patients undergoing assisted reproductive technology(ART). Luteinized granulosa cells were isolated from collected follicular fluid samples, and total RNA was extracted following standard protocols. Quantitative real-time polymerase chain reaction (qPCR) was then utilized to quantify the relative transcript levels of caspase-3, caspase-8, Bax, P53, PTEN, and Bcl-2 genes. RESULTS: Compared with patients with normal ovarian reserve (NOR), those with diminished ovarian reserve (DOR) exhibited significantly fewer antral follicles, retrieved oocytes, fertilized oocytes, high-quality embryos, blastocysts, and high-quality blastocysts, along with a markedly lower clinical pregnancy rate. Furthermore, the relative transcript level of caspase-3 was significantly upregulated in DOR patients and was notably higher in the non-pregnant subgroup. CONCLUSION: Notably, significantly higher transcript-level expression of caspase-3 in mural granulosa cells was correlated with DOR. Collectively, these findings suggest that the caspase-3 gene may play a role in regulating clinical pregnancy outcomes, thereby highlighting its potential as a molecular marker associated with ovarian reserve and pregnancy success.