• acute lymphoblastic leukaemia;
  • cyclophosphamide;
  • male fertility;
  • tubular fertility index


To study long-term testicular function following the treatment of acute lymphoblastic leukaemia (ALL) in childhood, 37 young adult males were assessed at two separate time points. The initial assessment was made by a wedge testicular biopsy after completion of treatment (median 9.7 years; range 4.1–16.3 years) and the subsequent assessment (median 18.6 years; range 15.4–26.8 years) consisted of the clinical examination of pubertal stage, measurement of serum gonadotrophins and testosterone and, in 19 patients, semen analysis.

All 37 men completed pubertal development normally and had a testosterone concentration within the normal adult range. Six men showed evidence of severe damage to the seminiferous epithelium, five were azoospermic and one, who did not provide semen for analysis, had a reduced mean testicular volume (11 mls; normal ≥15 mls) and a raised basal FSH level (13 IU 1--1; normal ≤6 IU I-1). All six men with germ-cell damage had received either cyclophosphamide or both cyclophosphamide and cytosine arabinoside as part of their chemotherapy regimen.

Approximately 10.7 years earlier all 37 men had undergone a testicular biopsy after completion of their chemotherapy. Morphological damage to the seminiferous epithelium had been calculated by estimating the tubular fertility index (TFI), which is the percentage of seminiferous tubules containing identifiable spermatogonia (age-matched normal = 100%).

Of the 11 males who had a TFI >50%, consistent with severe germ-cell damage, five had recovered normal germ-cell function more than 10 years later. Twenty-three of the 26 males, who had a TFI >50% at testicular biopsy, showed completely normal testicular function when reassessed subsequently, and in the remaining three men the results were inconclusive. It is concluded that the long-term outlook for male fertility after chemotherapy for ALL in childhood improves with time after treatment, but remains poor for at least 10 years in the more severely affected.