When 'idiopathic' is not idiopathic: imaging-based differentiation of azoospermia in the APHRODITE algorithm

The recently introduced APHRODITE criteria provide a structured framework for classifying and treating men with idiopathic male infertility, including azoospermic men in Group 2, who present with normal serum FSH and normal total testosterone concentrations and may be considered for hormonal therapy. However, a normal FSH concentration does not by itself distinguish obstructive from non-obstructive azoospermia, and obstructive azoospermia characteristically shares the same hormonal and testicular-volume profile that defines Group 2; non-obstructive azoospermia due to maturation arrest can present similarly, and hormonal therapy is unlikely to benefit these men either. Men with obstructive azoospermia or non-obstructive azoospermia due to maturation arrest who are misclassified in Group 2 may be exposed to prolonged, ineffective gonadotrophin therapy while definitive treatment is delayed. This commentary highlights this risk together with broader limitations of the APHRODITE criteria and proposes earlier imaging, using whichever modality is available at the treating centre, as a potential strategy to identify occult obstruction and avoid unnecessary hormonal therapy. This approach, however, requires prospective validation.