Male reproductive function in long‐term survivors of childhood cancer

Abstract

We evaluated reproductive function in 27 male long-term survivors of childhood cancer treated during the prepubertal and pubertal period. Sperm samples were obtained from 23 patients; four who refused to provide specimens indicated that they had fathered normal healthy children. Thirteen patients were 12 years old or younger at the time of diagnosis and initiation of therapy. Chemotherapy was calculated according to the cumulative amount of drug administered and correlated with the surface area. Sterility was associated with large doses of single alkylating agents or reduced doses administered with other agents in combination regimens. It was noted in boys treated in both the prepubertal and pubertal period. Sterility was also observed in patients who received testicular radiation alone or in combination with chemotherapy. However, it was not an inevitable consequence in all patients, despite treatment with similar or identical regimens. Fertility potential could not be predicted by clinical examination (testicular size) or gonadotrophin and testosterone values. The results were compared to published reports of treatment-induced sterility in adult males. Additional investigations are required to establish more accurate correlations of dosage with reproductive potential.

Reproduction following treatment for childhood leukemia: A population‐based prospective cohort study of fertility and offspring

“…Craniospinal radiation, resulting in scatter doses to the gonads, may also cause primary ovarian dysfunction, as shown in a study where ALL patients with this type of CNS prophylaxis were compared to a group with only cranial radiation [48]. Doses of 400 cGy to the ovaries may result in permanent sterility in young females [44,47,48], and doses of 140-300 cGy may cause permanent aspermia in males [33,42,44]. Reduced testicular size and impaired sperm production have been associated both with cranial and testicular radiation [49].…”

“…This effect may to some extent be dose related and has been observed in males treated before as well as during and after puberty [3, 38,[40][41][42][43]. The concept that the prepubertal testis may be less susceptible remains to be proven in humans; some studies suggest a higher risk in the sexually more mature patients [33], others show no age relationship [35,39,42]. Although return of spermatogenesis may occur even after a prolonged period of time [3,34,41], a fertility deficit after alkylating agents has been shown in long-term survivors [33].…”

Preservation of Fertility in Pediatric and Adolescent Patients With Cancer

“…21 Subsequent follow-up studies of childhood, adolescent, and young adult cancer and bone marrow transplant survivors have further defined variables associated with decreased fertility after cancer treatment. 22 These variables include (1) older age and/or developmental maturity of the patient at the time of therapy, 23 (2) the type of therapy, 24 (3) the site of therapy, and (4) gender. For example, the administration of alkylating agents seems to involve more of a risk of infertility in boys compared with the same therapy administered to girls, 21 although the alkylating agents destroy the primordial ovarian follicles in a dosedependent manner.…”

Critical Windows of Exposure for Children's Health: The Reproductive System in Animals and Humans

“…The effects of exogenous agents on ovarian follide recruitment, growth, differentiation, and atresia are important to study. (126)(127)(128)(129). PMSG presumably acts through the ovary to induce estrogen synthesis, which acts on the brain to increase the number of synapses per unit area of the ARCN.…”

“…Germ cells in the prepubertal testis are at least as sensitive to cytotoxic agents as in the adult (66). In one study of long-term survivors of childhood cancer, 6 of 13 patients treated prepubertally had a normal or near-normal reproductive state compared to 7 of 14 treated postpubertally (129). Interestingly, tests to detect abnormal testicular function, such as basal levels of gonadotropins and gonadotropin response to GnRH, are unlikely to detect testicular damage in prepubertal boys (130).…”