Challenges in differential diagnosis between obstructive and non-obstructive azoospermia

Background: Some cases of non-obstructive azoospermia(NOA) are characterized by normal clinical parameters, including testicular volume and levels of reproductive hormones, mimicking obstructive azoospermia(OA).Methods: We performed a retrospective review of a consecutive series of 1417 patients undergoing primary surgical sperm retrieval between 2014 and 2023.Follicle-stimulating hormone(FSH) level below 7.6 IU/l and normal testicular size with a long axis measurement >4.6 cm were used as criteria to suspect OA.Results: Four hundred and eighteen patients with normal testicular volume and FSH levels had an initial diagnosis of OA. Among them, 243(58.1%) had histological signs of spermatogenic dysfunction, and 175(41.9%) had true OA. One hundred eleven patients had long-standing obstruction(median:16.5 years) with a median Bergmann–Kliesch score(BKS) of 5(interquartile range [IQR]: 4–6) and 100% sperm retrieval rate(SRR), though some required microdissection testicular sperm extraction(micro TESE). Fifty-eight patients with a history of epididymo-orchitis had a median BKS of 4(IQR: 2–6) and100% SRR. Twenty patients with a history of unjustified medical treatment for male infertility had a median BKS of 3(IQR: 1–4) and 80% SRR. Fifty-four patients had uniform maturation arrest with a 5.5% SRR on micro TESE.Conclusion: Men with normal testicular volume and FSH level may have evidence of spermatogenic failure on pathology. Patients with complicated seminal tract obstruction commonly have hypospermatogenesis, but true NOA caused by uniform maturation arrest may also be observed. Patient counseling for suspected OA should not be overly optimistic, and couples should be warned about possibility of conversion to micro TESE and risks of negative sperm retrieval.