# Fertility in boys and young men treated for cancer, including testicular tissue banking

Source: https://onco.cc/technologies/rejuv-paed-fertility-male/  
OnCo record `rejuv-paed-fertility-male` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Male survivors were about half as likely as their brothers to father a child, and the causes are specific: testicular radiotherapy above 7.5 gray, and high cumulative cyclophosphamide, ifosfamide, procarbazine or cisplatin. A young man with none of those was no less likely than his brother. Sperm banking works; tissue banking before puberty has produced no births.

## Summary

The numbers that matter, from 6,224 male survivors aged 15 to 44 who were not surgically sterile, compared with siblings in the Childhood Cancer Survivor Study: the hazard ratio for ever siring a pregnancy was 0.56. Risk was concentrated by exposure. Radiotherapy of more than 7.5 gray to the testes carried a hazard ratio of 0.12; the highest tertile of cumulative alkylating agent dose or of cyclophosphamide, 0.42; procarbazine, 0.48 in the second tertile and 0.17 in the third. The result that should be told to every family is the control comparison: for survivors with an alkylating agent dose score of zero, no hypothalamic or pituitary radiation and no testicular radiation, the hazard ratio against siblings was 0.91 (95 per cent confidence interval 0.73 to 1.14, P = .41). No detectable reduction at all.

The later analysis of 10,938 survivors confirmed and extended this: male survivors had a hazard ratio of 0.63 (0.58 to 0.68) for pregnancy and 0.63 (0.58 to 0.69) for a livebirth, with reduced likelihood associated with upper-tertile cyclophosphamide (0.60), ifosfamide (0.42), procarbazine (0.30) and cisplatin (0.56), and a cyclophosphamide equivalent dose relationship of 0.82 (0.79 to 0.86) per 5,000 mg/m2.

Testosterone is a separate question from sperm. Leydig cells are more radioresistant than germ cells, so a young man can be infertile with normal testosterone, or, after higher doses, need testosterone replacement as well. In the St Jude Lifetime Cohort the estimated cumulative prevalence of Leydig cell failure at age 50 among men at risk was 31.1 per cent (27.3 to 34.9). The International Guideline Harmonization Group's 2017 male gonadotoxicity recommendations, developed with PanCareSurFup by a panel of 25 experts, cover both, and state that they "reveal the paucity of high-quality evidence, highlighting the need for further targeted research".

What can be done before treatment. Sperm banking is cheap, quick, effective and under-offered; it is the standard for any post-pubertal boy or young man, and the only real obstacles are that nobody raised it and that the appointment was not made in time. For a boy who cannot yet produce sperm, the only option is testicular tissue cryopreservation, and it remains experimental. The largest coordinated experience banked tissue from 189 patients between January 2011 and November 2018 across a network of academic centres, average age 7.9 years (standard deviation 5), range 5 months to 34 years. The indication was a malignancy in 118, a blood disorder in 45 and another condition in 26. Thirty-nine per cent (74 patients) had already started chemotherapy before the biopsy. Of 189 patients, 137 were analysed for the presence of germ cells and germ cells were confirmed in 132. The authors state the limit plainly: "The function of those spermatogonia was not tested." No child has yet been born from human testicular tissue frozen before puberty. Families should be offered it on that basis and not another.

What comes back, and when: spermatogenesis often recovers, over one to five years and sometimes longer, because spermatogonial stem cells can repopulate the tubules if enough survive. That is why a semen analysis at one year is not the final answer and why contraception still matters. Recovery is unlikely after testicular irradiation above about the threshold above or after transplant conditioning. Leydig cell function that has failed does not return, and testosterone replacement is the treatment.

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-10-02
- Tags: rejuvenation; survivorship; paediatric; late-effects; evidence:moderate
- Principle: Spermatogonial stem cells divide continuously and are therefore highly sensitive to alkylating agents and radiation, but a surviving population can repopulate the seminiferous tubules, which is why fertility often returns after moderate exposure and never after an ablative one. Leydig cells divide rarely and tolerate more, so testosterone production usually outlasts sperm production. Tissue banking before puberty aims to preserve spermatogonial stem cells for a future technique, which is why it is offered as research rather than as treatment.
- Strengths: Risk is concentrated in identifiable exposures, so most survivors can be reassured specifically; Sperm banking is simple, cheap and effective where it is offered in time; Harmonised international surveillance recommendations cover both sperm and testosterone
- Limitations: No human birth has yet resulted from testicular tissue frozen before puberty; Thirty-nine per cent of boys in the largest banking series had already started chemotherapy; Sperm banking is still missed when treatment starts urgently

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Semen_cryopreservation
- Fertility of male survivors of childhood cancer (CCSS) (JCO 2010): https://doi.org/10.1200/JCO.2009.24.9037
- Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999 (CCSS) (Lancet Oncol 2016): https://doi.org/10.1016/S1470-2045(16)00086-3
- Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers (Hum Reprod 2019): https://doi.org/10.1093/humrep/dez043
- Recommendations for gonadotoxicity surveillance in male childhood, adolescent and young adult cancer survivors (IGHG with PanCareSurFup) (Lancet Oncol 2017): https://doi.org/10.1016/S1470-2045(17)30026-8
- Fertility preservation for male patients with childhood, adolescent and young adult cancer: PanCareLIFE and IGHG recommendations (Lancet Oncol 2021): https://doi.org/10.1016/S1470-2045(20)30582-9
- Clinical ascertainment of health outcomes among adults treated for childhood cancer (SJLIFE) (JAMA 2013): https://doi.org/10.1001/jama.2013.6296

## Connected records

- collections: [International Guideline Harmonization Group for late effects of childhood cancer](https://onco.cc/collections/ighg/), [PanCareSurFup and the European survivor cohorts](https://onco.cc/collections/pancaresurfup/)
- trials: [Childhood Cancer Survivor Study (CCSS)](https://onco.cc/trials/ccss/)
- ideas: [Default fertility preservation referral for every patient under 40 before treatment](https://onco.cc/ideas/idea-acc-default-fertility-preservation-referral/)
- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Childhood cancers (all types)](https://onco.cc/cancers/childhood-cancers/), [Ewing sarcoma](https://onco.cc/cancers/ewing-sarcoma/), [Germ cell tumours of childhood and adolescence (extracranial and CNS)](https://onco.cc/cancers/paediatric-germ-cell-tumours/), [Hodgkin lymphoma](https://onco.cc/cancers/hodgkin-lymphoma/), [Testicular germ cell tumours](https://onco.cc/cancers/testicular/)
- fronts: [Hormonal Therapy](https://onco.cc/fronts/hormonal/), [Recovery & Rejuvenation](https://onco.cc/fronts/rejuvenation/), [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- technologies: [How much illness childhood cancer survivors carry, and at what age](https://onco.cc/technologies/rejuv-paed-chronic-disease-burden/), [Oncofertility and fertility preservation](https://onco.cc/technologies/fertility-preservation/), [Testosterone after cancer treatment in men](https://onco.cc/technologies/testosterone-after-cancer-treatment/), [The Children's Oncology Group Long-Term Follow-Up Guidelines](https://onco.cc/technologies/rejuv-paed-cog-ltfu-guidelines/), [The pituitary, puberty and the hypothalamic axis after cranial radiotherapy in childhood](https://onco.cc/technologies/rejuv-paed-pituitary-and-puberty/), [Total body and total marrow irradiation](https://onco.cc/technologies/total-body-irradiation/), [Who gets told about fertility before treatment, and who does not](https://onco.cc/technologies/rejuv-access-fertility-preservation/)
- terms: [Allogeneic stem cell transplant (allo-SCT)](https://onco.cc/terms/allogeneic-transplant/), [Fertility preservation before lymphoma treatment: a decision with a deadline in days](https://onco.cc/terms/lymphoma-decision-fertility-timing/), [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/)
- drugs: [Busulfan](https://onco.cc/drugs/busulfan/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/), [Procarbazine](https://onco.cc/drugs/procarbazine/)
- bottlenecks: [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)

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