The effects of relatively low-dose single fraction irradiation on spermatogenesis in healthy fertile men have been well documented (6) and are illustrated in Fig. 1. The more immature cells are more radiosensitive, with doses as low as 0.1 Gy causing morphological and quantitative changes to spermatogonia. Doses of 2 to 3 Gy result in overt damage to spermatocytes, leading to a reduction in spermatid numbers. At doses of 4 to 6 Gy, numbers of spermatazoa are significantly decreased, implying spermatid damage. The decline in sperm count after damage to more immature cells, with doses of up to 3 Gy, takes 60 to 70 d, with doses more than 0.8 Gy resulting in azoospermia and doses less than 0.8 Gy giving rise to oligospermia. A much faster fall in sperm concentration occurs after doses of 4 Gy and higher because of damage to spermatids.
Time to recovery
Time to onset of oligo/azoospermia
Azoospermia 60 days
Azoospermia < 60 days
Stage of germ cells damaged
Radiation dose 1 1 1 1 1 1
Fig. 1. Impairment of spermatogenesis after single-dose irradiation: the effect of radiation dose on stage of germ cell damage and time to onset and recovery from germ cell damage. (Adapted from ref. 6.)
Spermatogenesis recovery occurs from surviving stem cells (type A spermatogonia) and is dependent on the radiation dose. Complete recovery, as indicated by a return to pre-irradiation sperm concentrations and germinal cell numbers, occurs within 9 to 18 mo after 1 Gy or less, 30 mo for 2 to 3 Gy, and 5 yr or more for doses of 4 Gy and above.
Animal data suggest that fractionation of radiotherapy increases its gonadal toxicity, and the evidence suggests that this is also the case in humans. Speiser et al. (36) studied 10 patients who received a testicular dose of radiation of 1.2 to 3 Gy in 14 to 26 fractions during inverted Y-inguinal field irradiation for Hodgkin's disease. All patients were azoospermic after treatment, and recovery was not seen in a single patient, despite follow-up of more than 15 mo in 4 patients and up to 40 mo in 1 patient. An update of these data published in 1994 (37) revealed no recovery of spermatogenesis in patients receiving doses of 1.4 to 2.6 Gy after 17 to 43 mo follow-up, but a return of fertility in the 2 patients with testicular radiation doses of 1.2 Gy, suggesting that this may represent a threshold for permanent testicular damage. Hahn et al. (38) carried out serial semen analysis on 11 patients with cancer who had received large pelvic field irradiation or interstitial 125I seeds implanted into the prostate gland. The dose of radiation to the testis was 1.18 to 2.28 Gy delivered in 24 to 34 fractions. All patients became azoospermic, and recovery to oligospermia (three men) or normospermia (two men) was only seen in five patients. The other six remained azoospermic during a follow-up period of 35 to 107 wk.
However, lower doses of radiation to the testes are associated with better recovery rates for spermatogenesis. Centola et al. (37) reported a return of spermatogenesis in all 8 patients who received radiation doses of 0.28 to 0.9 Gy for testicular seminoma, with 4 out of 5 reviewed at 12 mo having normal sperm counts. Kinsella et al. (39) published
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