Follicular kisspeptin-VEGF axis in polycystic ovary syndrome and ovarian hyperstimulation syndrome

Polycystic ovary syndrome (PCOS) and ovarian hyperstimulation syndrome (OHSS) are characterized by excessive follicular activity and profound alterations in the ovarian microenvironment. Kisspeptin and vascular endothelial growth factor (VEGF) play central roles in the regulation of folliculogenesis, angiogenesis, vascular permeability, and ovarian responsiveness. This study aimed to compare follicular fluid levels of Kisspeptin-1, Kisspeptin-54, and VEGF among women with PCOS, women who developed OHSS, and normoresponder controls, and to investigate their associations with established markers of ovarian response.

In this retrospective cross-sectional study, 90 women undergoing IVF treatment were stratified into three groups: normoresponder controls (n = 30), women with PCOS (n = 30), and patients who developed OHSS (n = 30). Follicular fluid samples were collected at the time of oocyte retrieval. Concentrations of Kisspeptin-1, Kisspeptin-54, and VEGF were quantified using validated enzyme-linked immunosorbent assay (ELISA) methods. Clinical, hormonal, and embryological parameters were collected and analyzed using group comparisons, correlation analyses, and multivariable logistic regression models.

Follicular fluid concentrations of Kisspeptin-1, Kisspeptin-54, and VEGF differed significantly among study groups (all p < 0.001), demonstrating a progressive increase from normoresponder controls to women with PCOS and those who developed OHSS. Kisspeptin-54 and VEGF exhibited strong positive correlations with established indicators of ovarian response, including AMH, AFC, trigger-day estradiol levels, total oocyte yield, MII oocyte count, and the number of good-quality embryos (r = 0.41-0.78, all p < 0.001). In multivariable logistic regression analyses, Kisspeptin-54 (OR = 1.031) and VEGF (OR = 1.008), together with AFC, AMH, trigger-day estradiol, and total oocyte count, remained significantly associated with OHSS occurrence (all p < 0.01).

Follicular fluid levels of Kisspeptin-1, Kisspeptin-54, and VEGF are significantly elevated in ovarian hyperresponse conditions and exhibit strong associations with key indicators of ovarian stimulation outcomes. These findings suggest that Kisspeptin-54 and VEGF reflect the biological features of ovarian hyperresponsiveness and may serve as complementary biomarkers of the follicular microenvironment, rather than clinically actionable predictors of OHSS.