Male fertility in long‐term survivors of childhood acute lymphoblastic leukaemia

Abstract

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)

Effect of childhood cancer treatment on fertility markers in adult male long‐term survivors

“…Several studies have shown an impaired gonadal function in adult male survivors of childhood cancer [4,5]. Post-treatment gonadal damage showed to be depending on the type of used agents and cumulative dosages administered during childhood [6][7][8]. Usually, studies were based on one type of malignancy and treatment protocol and had limited number of survivors included [6][7][8].…”

“…Post-treatment gonadal damage showed to be depending on the type of used agents and cumulative dosages administered during childhood [6][7][8]. Usually, studies were based on one type of malignancy and treatment protocol and had limited number of survivors included [6][7][8]. Age at time of treatment was suggested to give some protection against chemotherapy induced gonadal damage due to quiescent stage of the testis in the prepubertal age [9].…”

Transplantation of spermatogonial stem cells isolated from leukemic mice restores fertility without inducing leukemia

“…Furthermore, more than half of the long-term survivors are not infertile and do not need to preserve spermatogonial stem cells (3,4). Alkylating agents and radiation therapy for testes are high-risk factors for infertility (4,28,29), but patients who need radiation therapy as a pretreatment for bone marrow transplantation have, among childhood leukemic patients, poor prognoses (30) and are in the minority of patients with childhood leukemia. This procedure should be strictly limited to candidates for preservation of spermatogonial stem cells.…”

Doxorubicin Induces Apoptosis in Germ Line Stem Cells in the Immature Rat Testis and Amifostine Cannot Protect against This Cytotoxicity

“…Male infertility is one of these major effects (1-3), but little is known about the mechanisms by which chemotherapeutic agents used to treat childhood cancer damage spermatogenesis in the prepubertal human testis. Permanent tubular damage may first become apparent during puberty when size of the testis remains prepubertal and sperm production does not initiate (1,4). The lack of appropriate methodology for detecting early cytotoxic damage to the immature testis has made it difficult to identify the exact maturational events on which these anticancer drugs exert their gonadotoxicity.…”