Systematic Review of the Gonadotoxicity and Risk of Infertility of Soft Tissue Sarcoma Chemotherapies in Pre- and Postpubertal Females and Males
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References 43 publications
Long-term effects on fertility after central nervous system cancer: A systematic review and meta-analysis
Background CNS cancer represents a common group of solid tumors in childhood & young adults, and less frequently in adults aged 30-40. Due to treatment advancements with increasing survival rates, disorders of the hypothalamus-pituitary-axis have become increasingly relevant for patients' future fertility plans. Most guidelines recommend that physicians should counsel their patients about fertility prognosis before initiating gonadotoxic therapy. However, for fertility preservation measures, gonadal toxicity as the only relevant risk factor has not yet been systematically reviewed. Methods A systematic literature search was performed in Medline, Embase and Cochrane in January 2024. The systematic review included studies of patients who had undergone treatment for all types of malignant CNS cancer. The outcomes were defined as clinically relevant gonadal toxicity as well as preserved fertility. The study adheres to the PRISMA guidelines. Results The qualitative analysis included 31 studies with a total of 4590 patients after CNS cancer. The overall pooled prevalence of gonadal toxicity was found to be 20% (95% CI: 10-34%). Preserved fertility was present in 75% (95% CI: 64-83%) of the patients and was maintained after at least five years following treatment (75%, 95% CI: 46-91%). Conclusions This initial meta-analysis provides a basis for fertility counselling after diverse CNS cancer treatments. Due to the high heterogeneity of the study population and lack of individual patient data on fertility outcomes, it is not possible to provide an exact estimation of the fertility prognosis following a specific treatment. Thus, fertility preservation measures should still be recommended.
Long-term effects on fertility after central nervous system cancer: A systematic review and meta-analysis
Background CNS cancer represents a common group of solid tumors in childhood & young adults, and less frequently in adults aged 30-40. Due to treatment advancements with increasing survival rates, disorders of the hypothalamus-pituitary-axis have become increasingly relevant for patients' future fertility plans. Most guidelines recommend that physicians should counsel their patients about fertility prognosis before initiating gonadotoxic therapy. However, for fertility preservation measures, gonadal toxicity as the only relevant risk factor has not yet been systematically reviewed. Methods A systematic literature search was performed in Medline, Embase and Cochrane in January 2024. The systematic review included studies of patients who had undergone treatment for all types of malignant CNS cancer. The outcomes were defined as clinically relevant gonadal toxicity as well as preserved fertility. The study adheres to the PRISMA guidelines. Results The qualitative analysis included 31 studies with a total of 4590 patients after CNS cancer. The overall pooled prevalence of gonadal toxicity was found to be 20% (95% CI: 10-34%). Preserved fertility was present in 75% (95% CI: 64-83%) of the patients and was maintained after at least five years following treatment (75%, 95% CI: 46-91%). Conclusions This initial meta-analysis provides a basis for fertility counselling after diverse CNS cancer treatments. Due to the high heterogeneity of the study population and lack of individual patient data on fertility outcomes, it is not possible to provide an exact estimation of the fertility prognosis following a specific treatment. Thus, fertility preservation measures should still be recommended.
Oncological treatments have limited effects on the fertility prognosis in testicular cancer: A systematic review and meta‐analysis
BackgroundTesticular 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.ObjectivesTo close the gap of data regarding gonadotoxicity of testicular cancer therapies to enable more accurate counselling regarding fertility preservation.Materials and methodsA 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.ResultsThe 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%).ConclusionSo 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.
Long-Term Effects on Gonadal Function After Treatment of Colorectal Cancer: A Systematic Review and Meta-Analysis
Background: The incidence of colorectal cancer (CRC) is increasing in the population under 50 years of age, with more than 10% of cases occurring in young adults. Fertility preservation counseling has therefore received increased attention in this younger patient population. The treatment of CRC is often based on multimodal therapies, including surgery, radiotherapy, chemotherapy, and, more recently, immunotherapy, which makes it difficult to estimate the expected effect of treatment on fertility. We, therefore, systematically analyzed the published literature on the gonadotoxic effects of CRC treatments to better advise patients on the risk of infertility and the need for fertility preservation measures. This systematic review and meta-analysis are part of the FertiTOX project, which aims to reduce the data gap regarding the gonadotoxicity of oncological therapies. Objectives: The aim of this review and meta-analysis is to evaluate the potential impact of CRC therapies on gonadal function to allow more accurate counseling regarding the risk of clinically relevant gonadotoxicity and the need for fertility preservation measures before oncological treatment. Materials and Methods: A systematic literature search was conducted in Medline, Embase, the Cochrane database of systematic reviews, and CENTRAL in March 2024. A total of 22 out of 4420 studies were included in the review. Outcomes were defined as clinically relevant gonadotoxicity, indicated by elevated follicle-stimulating hormone (FSH) and/or undetectable anti-Müllerian hormone (AMH) levels and/or the need for hormone replacement therapy in women and azoo-/oligozoospermia and/or low inhibin B levels in men. Studies with fewer than nine patients were excluded from the meta-analysis. Results: The qualitative analysis included 22 studies with 1634 subjects (775 women, 859 men). Treatment consisted of active surveillance after surgery (37.7%), chemotherapy (12.7%), radiation (0.2%), or radiochemotherapy (53.9%). In 0.5%, the therapy was not clearly described. The meta-analysis included ten studies and showed an overall prevalence of clinically relevant gonadotoxicity of 23% (95% CI: 13–37%). In women, the prevalence was 27% (95% CI: 11–54%), and in men, 18% (95% CI: 13–26%). A subanalysis by type of CRC was only possible for rectal cancer, with a prevalence of relevant gonadotoxicity of 39% (95% CI: 20–64%). In patients undergoing chemotherapy exclusively, the prevalence was 4% (95% CI: 2–10%). In those receiving only radiotherapy, the prevalence was 23% (95% CI: 10–44%); in contrast, it reached 68% (95% CI: 40–87%) in patients who received radiochemotherapy. Conclusions: This first meta-analysis of the clinically relevant gonadotoxicity of CRC therapies provides a basis for counseling on the risk of infertility and the need for fertility preservation measures. Despite the low prevalence of gonadotoxicity in cases receiving chemotherapy alone, fertility preservation is still recommended due to the uncertainty of subsequent therapy and the lack of large longitudinal data on individual treatment effects. Further prospective studies are needed to investigate the impact of CRC treatment on gonadal function and estimate the effect of new treatment modalities, such as immunotherapies.
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