knowledge was not demonstrated before. High seminal plasma iron can lessen sperm motility to 10% of normal, thus significantly affecting reproductive potential [8]. Further, the elevated systemic NTBI and LPI and low seminal GSH in our patients, correlating with sperm motility, imply that iron-induced oxidative stress may have a major role in the subfertility often detected in TDT men, beyond the hypogonadism caused by iron in the pituitary gland. Indirect evidence for seminal oxidative stress in TDT men was suggested [9]. In nonthalassemia subfertile men low seminal GSH levels were present, while normal GSH levels were associated with better sperm qualities [10]. Our results of normal sperm DNA fragmentation, an important measure for fertilization rate, contradict previous findings of increased sperm DNA fragmentation in TDT men [1,11]. It is possible that the relative low iron burden and normal seminal GSH levels found in our three patients were protective against increase DNA fragmentation. If confirmed in a larger study, it could suggest better preserved sperm quality in patients with consistent good iron chelation habits. Alternatively, diminished sperm DNA integrity was attributed to the use of the iron chelator desferroxamine [11,12], while our three patients were not using this chelation agent. Additionally, low seminal plasma zinc levels detected in most our patients also affects fertility, as zinc is an important micronutrient for DNA repair during spermatogenesis. In males, low zinc levels adversely affected fertilization ability that improved with increase in dietary zinc intake [5,13]. Since zinc deficiency is common in TDT [14] examining the effect of increase zinc intake in TDT men, even with apparent normal plasma levels may be warranted.This study suggests that individuals with high iron burden have decreased pituitary volume and low gonadotropin levels; additionally their seminal environment has a detrimental effect on sperm vitality and quality. In patients with consistent adherence to iron chelation the pituitary size and fertility measures are better preserved. The value of serial measures of pituitary volume and iron concentration needs further study but may prove to have a better predictive value for fertility potential than gonadotropin levels. Aggressive iron reduction along with antioxidant and zinc supplementation could assist with fertility preservation. The use of antioxidants supplementation was shown to improve sperm qualities, though the overall effectiveness remains controversial [4,15]. Clarifying the risk thresholds of these causative factors in larger studies can assist in treatment interventions and fertility preservation.