High risk of azoospermia in men treated for childhood cancer

Abstract

Childhood cancer survivors (CCS) have an increased risk of impaired spermatogenesis, but data regarding the disease- and treatment-related risk factors of azoospermia are scarce. Such information is crucial both for counselling CCS and for selecting patients for testicular tissue cryopreservation. The proportion of azoospermic men in CCS was 18% [95% confidence interval (CI): 12-26], specifically for leukaemias (19%; 95% CI: 5.5-42), Hodgkin's disease (53%; 95% CI: 29-76), non-Hodgkin's lymphoma (11%; 95% CI: 0.28-48) and testicular cancer (11%; 95% CI: 0.28-48). In CCS treated with high doses of alkylating agents, the proportion of azoospermic men was 80% (95% CI: 28-99) and if radiotherapy was used additionally, the proportion was 64% (95% CI: 35-87). In CCS with subnormal Inhibin B levels, the proportion of azoospermic men was 66% (95% CI: 47-81) and for those with elevated follicle-stimulating hormone (FSH) levels, the proportion was 50% (95% CI: 35-67). Among CCS with subnormal testicular volume (≤ 24 mL), azoospermia was found in 61% (95% CI: 39-80) of the cases. Most childhood cancer diagnoses are associated with an increased risk of azoospermia, especially in CCS receiving testicular irradiation, high doses of alkylating drugs and other types of cytotoxic treatment, if combined with irradiation. Inhibin B, FSH and testicular volume can be used as predictors for the risk of azoospermia.

Primary Gonadal Insufficiency in Male and Female Childhood Cancer Survivors in a Long-Term Follow-Up Clinic

“…10,39 In such cases, inhibin B, the most accurate serum marker of impaired spermatogenesis, may provide a more acceptable alternative for fertility assessment. 12 In females, AMH, a serum marker of ovarian function, is a convenient and superior adjunct or alternative to FSH due to its consistency throughout the menstrual cycle. 23,40 Once a diagnosis of PGI has been established, management includes HDT, fertility preservation, and fertility treatment if indicated.…”

“…Therefore, normal pubertal development and sexual function may be preserved. 7,11,12 In females, <40 years of age, PGI is characterized by primary amenorrhoea (pre-pubertal) or secondary amenorrhoea (for >4 months), elevated FSH, and low estradiol. 13 Intermittent reproductive capacity may be preserved, as some ovarian function is retained in almost 50% of females with PGI and 5%-10% conceive spontaneous viable pregnancies.…”

Estrogen receptor α single nucleotide polymorphism modifies the risk of azoospermia in childhood cancer survivors

“…Recently, we have published data on treatment-related risk of azoospermia in this patient cohort [5]. The proportion of CCSs with azoospermia was 18% for the whole group, and as high as 80% in the subgroup receiving potentially sterilizing doses of alkylating drugs ( Table 1).…”

“…For the 40 CCSs being in the particular high-risk group for development of azoospermia after high-dose alkylating drugs or lower doses of these compounds combined with irradiation [5], the corresponding ORs are presented in Table 4.…”

“…It is well known that the risk for permanent infertility is most pronounced in boys treated with alkylating drugs [4,5], but good prognostic markers for predicting the impact of childhood cancer treatment on future fertility potential are lacking. It is also well known that individuals who have received identical treatment may differ in terms of semen quality, some having preserved sperm production, whereas approximately 20% develop azoospermia afterwards [6], indicating that some individuals might be more sensitive to the sterilizing effect of course of therapy, possibly due to genetic factors.…”