Fertility preservation in children, especially girls, before undergoing chemotherapy involves timely and tailored fertility preservation strategies based on pubertal status, treatment urgency, and gonadotoxic risk assessment.
For prepubertal girls, the primary and currently most viable fertility preservation method is ovarian tissue cryopreservation (OTC), which involves laparoscopic surgical removal and freezing of ovarian cortex containing primordial follicles prior to gonadotoxic therapy initiation NICE CG156,Hafele et al. 2025 Rahman et al. 2025. OTC does not require ovarian stimulation, making it feasible even when cancer treatment cannot be delayed. It has been demonstrated to enable puberty induction and live births after transplantation, although the risk of malignant cell contamination must be considered and carefully evaluated Purandare et al. 2025 Hafele et al. 2025 Rahman et al. 2025. Ovarian transposition (surgically relocating ovaries outside the radiation field) is another adjunct surgical approach when pelvic radiotherapy is planned, aiming to preserve ovarian endocrine function from radiation damage; however, it does not protect from chemotherapy toxicity and is preferably performed before radiotherapy NICE CG156 Yazdani et al. 2026.
For postpubertal girls and adolescents who have reached or are nearing menarche, established methods include oocyte and embryo cryopreservation, which require controlled ovarian stimulation and egg collection. These methods can be offered when there is sufficient time before cancer treatment, and the patient is medically fit to undergo stimulation without worsening their condition NICE CG156,Hafele et al. 2025 Rahman et al. 2025. Gonadotropin-releasing hormone agonists (GnRHa) administration may be considered as a complementary ovarian suppression strategy during chemotherapy, though its protective effect remains inconclusive and is more supported in breast cancer contexts NICE CG156,Hafele et al. 2025 Rahman et al. 2025.
Before therapy initiation, discussing and documenting pubertal status, hormonal evaluations including anti-Müllerian hormone (AMH), FSH, and estradiol, help stratify fertility risk and tailor preservation strategies Hafele et al. 2025 Hafele et al. 2025. Importantly, counseling should be multidisciplinary and include the patient and family to support informed decisions, recognizing the experimental nature and associated uncertainties of some procedures like OTC in prepubertal girls ESHRE FP for Boys Working Group et al. 2025 NICE CG156,Hafele et al. 2025.
While gonadotoxic chemotherapy, notably alkylating agents such as cyclophosphamide, can cause premature ovarian insufficiency or failure, even in prepubertal girls who often develop normal secondary sexual characteristics, these interventions aim to preserve primordial follicles and thus future fertility potential SmPC Cyclophosphamide,SmPC Cyclophosphamide,SmPC Cyclophosphamide,SmPC Cyclophosphamide Rahman et al. 2025. Proactive fertility preservation is crucial as no safe dose threshold reliably predicts infertility, and all patients should be counseled about risks and options regardless of age or pubertal status NICE CG156,Hafele et al. 2025 Hafele et al. 2025.
Overall, the pathway is as follows: early fertility risk assessment involving oncologists, reproductive specialists, and pediatric endocrinologists; offering oocyte/embryo cryopreservation for postpubertal girls; offering ovarian tissue cryopreservation for prepubertal girls or when treatment urgency precludes stimulation protocols; considering ovarian transposition if pelvic radiotherapy is planned; and providing psychological and ethical counseling to patients and families with discussion of experimental nature, risks, and future fertility options NICE CG156,Hafele et al. 2025,Rahman et al. 2025 Rahman et al. 2025Purandare et al. 2025Yazdani et al. 2026.
Key References
- NICE CG156: Fertility problems: assessment and treatment
- SmPC: Cyclophosphamide 500 mg Powder for Solution for Injection or Infusion
- SmPC: Cyclophosphamide 2000 mg Powder for Solution for Injection or Infusion
- SmPC: Cyclophosphamide 1000 mg Powder for Solution for Injection or Infusion
- SmPC: Cyclophosphamide Seacross 2000 mg powder for solution for injection/infusion
- NICE CKS: Childhood cancers - recognition and referral
- NICE CKS: Crohn's disease
- NICE NG73: Endometriosis: diagnosis and management
- NICE CKS: Ovarian cancer
- NICE CKS: Pre-conception - advice and management
- (Guzy and Demeestere, 2017): Assessment of ovarian reserve and fertility preservation strategies in children treated for cancer.
- (ESHRE FP for Boys Working Group et al., 2025): ESHRE good practice recommendations on fertility preservation involving testicular tissue cryopreservation in children receiving gonadotoxic therapies†.
- (Purandare et al., 2025): Cancer and fertility management: FIGO best practice advice.
- (Hafele et al., 2025): Fertility Preservation in Pediatric Oncology: Results of a Single-Center Retrospective Study (2000-2018).
- (Rahman et al., 2025): From Survival to Parenthood: The Fertility Journey After Childhood Cancer.
- (Yazdani et al., 2026): Surgical approaches to fertility preservation in the cancer patient: current and future directions.