Association of the minimal cyclophosphamide equivalent dose and outcome of microdissection testicular sperm extraction in patients with persistent azoospermia after chemotherapy

Objective: To investigate whether the minimal cyclophosphamide equivalent dose (mCED), a novel approach for estimating alkylating agent exposure, is associated with the sperm retrieval rates by microdissection testicular sperm extraction (mTESE) in azoospermic postchemotherapy cancer survivors. Design: A retrospective cohort study conducted between 2002 and 2017. Setting: An academic medical center. Patients: A total of 28 azoospermic postchemotherapy cancer survivors who underwent mTESE. Interventions: Chemotherapy exposure and mCED calculation. Main Outcome Measures: The primary outcome was the association between the mCED and sperm retrieval rate using mTESE. The mCED value for each patient's regimen received was estimated using the lowest recommended dosing regimen from the range of recommended doses at the time of administration. Results: Spermatozoa were successfully retrieved in 11 (39.3%) of the patients. Age at the time of receiving chemotherapy and mCED were significant factors associated with sperm retrieval. An mCED of <4,000 mg/m² had a higher sperm retrieval rate (10/14, 71.4%) than an mCED of >4,000 mg/m² (0/8, 0). The hormone levels were not significantly different when comparing patients with and without successful sperm retrieval. Seminoma, nonseminomatous germ cell tumor, and acute lymphoblastic leukemia had favorable sperm retrieval rates—100% (2/2), 66.7% (2/3), and 66.7% (2/3), respectively—although the numbers of patients in each group were small. Conclusion: Among this cohort of patients with cancer who required chemotherapy regimens, successful sperm retrieval by mTESE was only noted among cancer survivors receiving an mCED of <4,000 mg/m².