Reproductive capacity in iron overloaded women with thalassemia major

Abstract

The pathophysiology of iron-induced compromised fertility in women with thalassemia major (TM) was evaluated in 26 adult TM females. Low gonadotropin secretion resulted in reduced ovarian antral follicle count and ovarian volume, but levels of anti-müllerian hormone (AMH), a sensitive marker for ovarian reserve independent of gonadotropin effect, were mostly normal. AMH correlated with non-transferrin-bound iron (NTBI), suggesting a role of labile iron in the pathogenesis of decreased reproductive capacity, possibly occurring in parallel to cardiac iron toxicity, as cardiac iron was associated with the presence of amenorrhea and with NTBI levels. AMH emerges as an important biomarker for assessment of reproductive capacity in TM, demonstrating that fertility is preserved in the majority of those younger than 30 to 35 years. AMH can be useful in future studies aiming at improved chelation for fertility preservation, whereas NTBI and labile plasma iron may be valuable for monitoring iron effect on the reproductive system.

Figure 1

AMH levels and AFC in TM women and normo-ovulatory controls. (A) AMH levels in the thalassemia women, 25 years and older (n = 23, red circles) were compared with normal controls (●; n = 759), showing that the slopes of the regression lines against age were not statistically different (P = .56). The slope was significant for the normal controls (P < .0001; 95% CI, −1.867 to −1.406) and for the thalassemia patients (P < .03; 95% CI, −2.323 to −0.1142), implying an association with age. There was a 5.0pM (95% CI, 13.4 to 26.8) difference between the group means. The levels in the thalassemia women were in the low-normal range of normal and dropped to lower levels in women older than 30 years. (B) Age-dependent AFC in thalassemia women and normal controls. AFC number includes all counted follicles 2-10 mm in size, in thalassemia women, and in the cohort of normal controls (n = 769).