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Ovarian function has been studied sequentially since 1975 in 19 patients treated in childhood for an intra-abdominal tumour with surgery and whole abdominal radiotherapy (total dose 30 Gy). Eleven patients received chemotherapeutic agents that are not known to cause gonadal dysfunction. All but one patient have developed ovarian failure with persistently elevated gonadotrophin levels (FSH and LH greater than 32 IU/litre) and low serum oestradiol values (less than 40 pmol/litre) before the age of 16 years. The majority (n = 12) did not progress beyond breast stage 1 without sex steroid replacement therapy. As the number of oocytes within the ovary declines exponentially by atresia from approximately 2,000,000 at birth to approximately 2000 at the menopause, we have been able to estimate that the LD50 for the human oocyte does not exceed 4 Gy.

Vcr alone is as effective for stage I FH tumors as the two-drug regimen used in the NWTS and International Society of Pediatric Oncology (SIOP) studies. Fractionation of Act-D is unnecessary. The poorer results for stage IV FH and UH patients compared with the NWTS may be due to treatment differences, such as the use of lung irradiation for stage IV FH patients in NWTS3, and/or to case selection bias.

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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 greater than or equal to 15 mls) and a raised basal FSH level (13 UI 1-1; normal less than or equal to 6 IU 1-1). 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%).(ABSTRACT TRUNCATED AT 250 WORDS)

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