Impact on Fertility Outcomes in Survivors after Oncological Treatment of Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis

PURPOSE: Non-Hodgkin lymphoma (NHL) is a heterogeneous group of cancers. Published recommendations and guidelines for fertility preservation are very general and heterogeneous. Therefore, a very first meta-analysis analyzing the worldwide-published data on the risk of infertility after treatment of NHL is required to better counsel patients regarding fertility issues and to develop further strategies to evaluate the gonadotoxicity of treatments in NHL. METHODS: A systematic literature search was conducted using Medline, Embase, and Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials (CENTRAL), including articles published since 2000. Exclusion criteria were cases with disease relapse, follow-up of <1 year, testicular NHL, studies with <40% reproductive markers, and case reports. A total of 4602 records were identified. For the systematic review, 58 studies met the inclusion criteria. In this meta-analysis, 51 studies were included. RESULTS: The prevalence of expected infertility is 27% (95% confidence interval [CI] 0.20-0.37) overall, 23% (95% CI: 0.14-0.35) in females, and 35% (95% CI: 0.27-0.44) in males. It is highest after chemotherapy and radiotherapy to the pelvis and testis ± bone marrow transplantation, 43% (95% CI: 0.20-0.69) in females and 57% (95% CI: 0.21-0.86) in males. After alkylating agents in females, it is 24% (95% CI: 0.17-0.34). CONCLUSION: The results of this review and meta-analysis indicate a broad heterogeneity of data regarding the risk of infertility. Therefore, fertility counseling and, if necessary, fertility preservation measures are mandatory before oncologic treatment for NHL. Prospective studies stratified by chemotherapy regimen and including new treatment regimens are urgently needed.