Male survivors of childhood, adolescent, and young adult cancers often experience persistent azoospermia due to gonadotoxic chemotherapy, impairing fertility. Microdissection testicular sperm extraction (mTESE) enables retrieval of viable sperm for assisted reproduction in these patients. This systematic review and meta-analysis evaluated the overall sperm retrieval rate (SRR) and identified clinical predictors of successful mTESE in men with post-chemotherapy azoospermia to inform fertility counseling and optimize treatment decisions.

A comprehensive literature search was conducted across PUBMED, EMBASE, Web of Science, and Cochrane databases covering studies published from January 2000 to December 2024, using terms related to chemotherapy, azoospermia, and testicular sperm extraction. Only English-language human studies were included. Eligible studies involved patients with post-chemotherapy non-obstructive azoospermia who underwent testicular sperm extraction or mTESE and reported sperm retrieval outcomes. Two reviewers independently screened studies, and data were extracted on cancer type, alkylating agent exposure, age at chemotherapy and mTESE, interval from chemotherapy to mTESE, testis size, and hormone profiles (FSH, LH, testosterone). Meta-analyses were performed using RevMan, and P-scores were applied to assess the certainty of evidence. Study reporting followed the PRISMA guidelines.

A total of 14 studies involving 459 patients with post-chemotherapy azoospermia were included, with pooled SRR of 43.8% (201/459). Among 123 patients exposed to alkylating agents, only 35 (28.5%) had successful sperm retrieval. Alkylating agent exposure (n=123) reduced success (28.5%, 35/123; OR 0.17, 95% CI 0.08–0.35, p<0.001, I²=9%). Age at mTESE (MD 0.64 years, 95% CI -0.42 to 1.69, p=0.24, I²=0%), age at chemotherapy (MD 3.23 years, 95% CI -0.71 to 7.18, p=0.10, I²=69%), interval to mTESE (MD -1.81 months, 95% CI -6.73 to 3.12, p=0.41, I²=80%), testis size, and hormone levels (FSH, LH, testosterone) showed no significant associations.

mTESE offers a 43.8% SRR for post-chemotherapy azoospermia, with alkylating agent exposure significantly lowering odds (OR 0.17, p<0.001). Age, chemotherapy-to-mTESE interval, testis size, and hormone levels were not predictive. These findings emphasize the alkylating agents’ impact on spermatogenesis and the need for early, tailored fertility counseling for cancer survivors pursuing assisted reproduction.