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Cyclophosphamide Gonadotoxicity Dose-Dependent Counselling — ESENeph MCQ

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ModerateRenal VasculitisCyclophosphamide Gonadotoxicity Dose-Dependent CounsellingESENeph

A 55-year-old man with CKD G3b (eGFR 34 mL/min/1.73m2) is diagnosed with ANCA-negative pauci-immune crescentic GN after presenting with rapidly progressive renal failure. During shared decision-making about induction immunosuppression (cyclophosphamide vs rituximab), the patient asks about the risk of infertility. He has not completed his family. What specific counselling is required regarding cyclophosphamide?

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Correct answer: C — Gonadotoxicity is dose-dependent — cumulative dose matters most

Cyclophosphamide gonadotoxicity is dose-dependent and cumulative. In males, the threshold for permanent azoospermia is approximately 7.5-10 g cumulative dose (though damage can occur at lower doses). The Euro-Lupus low-dose IV CYC protocol (500 mg fortnightly x6 = 3 g total) was partly developed to reduce this risk. Semen cryopreservation should be offered BEFORE starting treatment. Rituximab offers equivalent efficacy for remission induction (RAVE, RITUXVAS trials) without gonadotoxicity, making it preferred in this clinical scenario. Oral CYC carries higher cumulative exposure than pulsed IV regimens. GnRH agonist co-treatment may offer partial protection in females but is unproven in males.

Reference: KDIGO 2024 – AAV Guideline; Mok et al 2007 – Cyclophosphamide Gonadotoxicity; HFEA Guidance