Exploring zinc-α2-glycoprotein as a mediator of infertility in polycystic ovarian syndrome: a comparative study from a metabolic perspective

Introduction
Polycystic ovarian syndrome (PCOS) is a leading cause of infertility linked to insulin resistance and obesity. Zinc-2-glycoprotein (ZAG) is an adipokine involved in lipid metabolism and insulin sensitivity. We hypothesized that reduced ZAG serum levels among PCOS cases could predict fertility odds. The aim is to examine ZAG’s relationship with fertility parameters and to test its role as a predictor for fertility potential.

Material and methods
A comparative cross-sectional study recruited PCOS cases into two groups: the infertile and fertile group; n = 60 for each. Women’s anthropometric (age, body mass index – BMI, waist circumference) hormonal (follicle-stimulating hormone, luteinizing hormone, anti-Müllerian hormone (AMH), total testosterone, and prolactin) metabolic parameters and ZAG serum levels, estimated via ELIZA/ELISA were recorded.

Results
Body mass index was significantly high in infertile cases; ZAG levels were significantly lower among the infertile group (37.08 ±3.885 vs. 54.25 ±14.71 µg/ml; p < 0.0001). Zinc-α2-glycoprotein was inversely and significantly correlated to BMI, waist circumference (r = –0.81, –0.78; p < 0.0001), and all hormonal and metabolic parameters. Zinc-α2-glycoprotein cut-off value of > 42 µg/ml predicted fertility potential in PCOS, with 67% sensitivity, 97.50% specificity, and p < 0.0001, but it did not surpass AMH.

Conclusions
Zinc-α2-glycoprotein is a potential biomarker for fertility that links metabolic and reproduction dysfunction in PCOS women. It mediates 13.5% of obesity’s inverse effect on fertility. Restoring normal ZAG levels may improve fertility odds and can have prognostic value in following the therapy in those populations. Further longitudinal, larger-sized studies are recommended to explore newer diagnostic and prognostic avenues to improve reproduction potential among PCOS cases.