RESUMO
BACKGROUND: Testicular cancer is the most common solid tumour among young men in the reproductive phase. After completing cancer treatment, up to 77% of cancer survivors report an interest in paternity after completing cancer treatment. To preserve fertility, most guidelines recommend that physicians should counsel their patients about sperm cryopreservation before initiating gonadotoxic therapy. However, few studies have assessed fertility parameters after testicular cancer therapies over the last 20 years. OBJECTIVES: To close the gap of data regarding gonadotoxicity of testicular cancer therapies to enable more accurate counselling regarding fertility preservation. MATERIALS AND METHODS: A systematic literature search was conducted in Medline, Embase and Cochrane until December 2022. The systematic review included studies of men who had undergone all types of unilateral testicular cancer treatment, whereas the meta-analysis excluded studies with unspecified treatments, less than 10 patients for outcome evaluation or rare tumours. Infertility (i.e. azoospermia, failure to achieve paternity or the usage of cryosperm) was defined as outcome. RESULTS: The qualitative analysis included 30 studies with a total of 13,718 men after unilateral testicular cancer. Treatment comprised active surveillance after unilateral orchidectomy (32.7%), radiotherapy (23.1%), standard- or low-dose chemotherapy (33.7%) and high-dose chemotherapy (1.4%). Post-treatment spermiograms were analysed in 17 studies. The quantitative synthesis included 23 studies, revealing an overall pooled prevalence of infertility (95% CI) of 14% (9%-21%). Azoospermia occurred in 8% (6%-12%). For good-prognosis patients who received standard therapy, the overall prevalence of infertility was only 4% (2%-10%). CONCLUSION: So far, this very first meta-analysis of overall infertility prevalence provides the best approximation of fertility prognosis for men who have undergone testicular cancer therapy. Despite the low prevalence of infertility, it is still recommended to undergo sperm cryopreservation because of the uncertainty of the subsequent therapy and the lack of large longitudinal data on individual treatment effects.
RESUMO
Increasing awareness of gonadotoxicity in cancer treatments and infertility risk is essential for counseling young cancer patients. While fertility preservation options are available in many countries, limited data on gonadotoxicity hinder recommendations, especially for soft tissue cancers. This review, part of the FertiTOX project (www.fertitox.com), organized by FertiPROTEKT (www.fertiprotekt.com), aims to address this knowledge gap to improve fertility preservation guidance. We performed a systematic literature search on gonadotoxicity in soft tissue sarcoma (STS) cancer treatments. Only patients without metastases or recurrent disease were considered. "Suspected infertility" was defined based on low ovarian reserve parameters, low inhibin B levels, high gonadotropin concentration, gonadal dysfunction, amenorrhea, oligomenorrhea, azoospermia, or oligozoospermia due to limited infertility data. The study quality was assessed using the Newcastle-Ottawa Scale. The search yielded 3309 abstracts, with 138 undergoing full-text analysis. Eight studies on STS were included. Suspected infertility was observed in 20 of 28 females (71.4%, range 0-100%) and 38 of 63 males (60.3%, range 34.8-100%) with STS. Six of the eight studies received high-quality scores on the NOS, while two received a fair score. Our data suggest a high risk of infertility from chemotherapy in pre- and postpubertal STS survivors. This underscores the importance of considering fertility preservation measures when counseling these patients.
RESUMO
Data on gonadotoxicity of chemotherapies are essential to better counsel young females and males about the risk of infertility and to better indicate fertility preservation measures before cancer therapies. However, such data have not recently been reviewed for bone cancer. Therefore, a systematic literature search was conducted considering papers published since 2000. This study is part of the FertiTOX® project, which aims to improve the lack of data regarding gonadotoxicity of cancer therapies to enable more accurate counseling regarding fertility preservation. Only relapse-free women and men were included. Gonadotoxic therapy-induced suspected infertility was defined as very low anti-mullerian hormone, high gonadotropin concentration, amenorrhea, oligomenorrhea, azoospermia, or oligozoospermia. The quality of the individual studies was assessed using the Newcastle-Ottawa Scale (NOS). In total, 11 out of 831 studies were included in the review. Suspected infertility was found in 10/190 (5.1%, range 0%-66%) of female patients with osteosarcoma (six studies), in 24/46 (52.2%, range 46%-100%) of male patients with osteosarcoma (three studies), in 18/138 (13.0%, range 3%-18%) of female patients with Ewing's sarcoma (three studies), and in 34/38 (89.5%) of male patients with Ewing's sarcoma (one study). A risk calculation in relation to specific chemotherapies was not possible. Risk of suspected infertility tends to be higher in Ewing's sarcoma in which all patients received chemotherapies with alkylating agents. Two of the 11 included studies received a high NOS quality score, whereas the remaining nine studies received a low quality score, mainly because of the lack of a comparator group. Published data are too limited for precise estimation of the gonadotoxicity. However, data indicate clinically relevant risk for infertility, supporting counseling patients before chemotherapy about fertility preservation measures.