ESHRE Issues 44 Recommendations for Preserving Fertility in Boys Before Cancer Treatment

Cancer survivorship in children has improved dramatically, but gonadotoxic chemotherapy and radiotherapy can permanently destroy the spermatogonial stem cells (SSCs) that underpin future fertility. For postpubertal males, sperm banking offers a straightforward solution. For prepubertal boys and adolescents who cannot yet produce sperm, however, testicular tissue cryopreservation (TTC) is the only available strategy — and until now, no international consensus existed on how to perform it safely and consistently.

The ESHRE Working Group on Fertility Preservation for Boys conducted a systematic literature review through September 2024 using PubMed/MEDLINE and the Cochrane Library. A multidisciplinary panel — spanning paediatric oncology, reproductive endocrinology, andrology, surgery, tissue banking, stem cell science, nursing, and ethics — synthesized the evidence and reached consensus on 44 Good Practice Recommendations across six major domains. The draft underwent open stakeholder review, receiving 172 comments from 22 independent reviewers, all adjudicated before final publication.

A striking backdrop to the guidelines is rapid uptake of TTC: a recent international survey documented more than 3,000 procedures performed worldwide, with the number doubling over just five years. Despite this growth, clinical use of the cryopreserved tissue to restore fertility remains unproven in humans. The recommendations therefore distinguish clearly between established procedure (tissue banking) and experimental application (future transplantation or in vitro maturation), urging transparent patient and family counselling to set realistic expectations.

Key clinical recommendations address who should be offered TTC — primarily boys facing high-risk gonadotoxic regimens (e.g., alkylating agents above threshold doses, total body irradiation) where the risk of azoospermia exceeds ~50%. The guidelines specify that a multidisciplinary team is essential, with a designated 'Divisional Champion' to ensure timely referral before treatment begins. Surgical biopsy technique, volume of tissue retrieved, cryoprotectant protocols, quality control markers (SSC viability, somatic cell function), and biobanking standards are all addressed in detail. Importantly, the recommendations call for systematic histological assessment of biopsied tissue and for centres to maintain prospective registries tracking patient outcomes.

The working group explicitly highlights several unresolved research gaps: no human live birth has yet been reported from immature testicular tissue transplantation or in vitro maturation of SSCs; the oncological safety of autologous tissue retransplantation (risk of reintroducing malignant cells) is unresolved for haematological cancers; and optimal cryopreservation protocols remain debated. The guidelines therefore frame TTC as a procedure offered within an ethically robust, research-active framework rather than a routine clinical service — while also arguing that withholding the option deprives boys of their only available fertility insurance. Centres are urged to participate in national and European registries to accelerate the evidence base needed to transition from tissue storage to actual fertility restoration.