{"entity":{"id":"rejuv-tx-fertility-and-growth","kind":"technology","name":"Fertility, growth and what total body irradiation costs","aka":["infertility after transplant","premature ovarian insufficiency after HSCT","growth after total body irradiation","TBI late effects"],"tldr":"Transplant conditioning, and total body irradiation in particular, usually ends natural fertility and in children slows growth. The decisions that preserve the most are made before conditioning starts. A randomised trial in children with leukaemia tested replacing the radiation with chemotherapy and found the radiation worked better.","summary":"What happens to fertility. Myeloablative conditioning, whether with total body irradiation or high-dose alkylating agents, destroys the ovarian follicle reserve and the germinal epithelium of the testis in most recipients. A single-centre cross-sectional study of 102 young women aged 8 to 35 who had an allogeneic transplant reported premature ovarian failure in 88.2 per cent of those transplanted for acute myeloid leukaemia, 93.9 per cent for acute lymphoblastic leukaemia and 61.5 per cent for aplastic anaemia, with age at transplant the only factor independently associated on multivariate analysis. A larger retrospective study of 263 nulliparous women transplanted between 2012 and 2024 found secondary amenorrhoea in 228, 86.7 per cent, with natural recovery of menstruation in 35, 13.3 per cent; among 137 who received hormone replacement therapy, 134, 97.8 per cent, resumed menstruation, and over a median follow-up of 83.8 months 5 patients gave birth, one by natural conception and four using cryopreserved oocytes. Those are single-centre series from one country and the percentages should be read as the order of magnitude rather than as a universal rate, but the direction is consistent across every published series: for most people, natural fertility does not survive myeloablative conditioning.\n\nWhat can be done, and when. Everything useful happens before conditioning. OnCo covers the options on `fertility-preservation`: sperm banking, oocyte or embryo cryopreservation after a random-start stimulation that can be completed in around two weeks, ovarian tissue cryopreservation, which is the only option for pre-pubertal girls, and surgical transposition of an ovary out of a radiation field. A GnRH agonist before and during treatment is used in some settings; in the 263-patient series, pre-transplant GnRH agonist use was independently associated with menstrual recovery (odds ratio 0.06, 95 per cent CI 0.03 to 0.15, P less than 0.001), which is an observational association in a non-randomised series and is weaker evidence than the cryopreservation options. Hormone replacement after transplant treats the consequences of ovarian failure, bone loss, vasomotor symptoms, vaginal atrophy and cardiovascular risk, and is covered on `menopause-after-cancer-treatment` and `testosterone-after-cancer-treatment`.\n\nThe gap that recurs in every study of this is counselling, not technology. In a cohort of 32 pubertal survivors of transplant for sickle cell disease, 25 per cent of parent proxies and 45 per cent of patients reported that they had not been informed by a healthcare provider of the risk of infertility after transplant.\n\nGrowth in children. Total body irradiation reduces final adult height through three separate mechanisms: direct damage to the growth plates, growth hormone deficiency from irradiation of the hypothalamic-pituitary axis, and the effects of hypothyroidism and gonadal failure on the pubertal growth spurt. Growth hormone deficiency after cranial or total body irradiation is treatable with growth hormone, which is why growth monitoring and endocrine assessment are in the screening recommendations for children after transplant. The paediatric survivorship cohorts belong to another facet of this round; what is specific here is that transplant concentrates several growth-limiting exposures at once.\n\nThe FORUM trial, and why this is a trade rather than a choice. FORUM randomised children with acute lymphoblastic leukaemia in complete remission, aged 4 to 21 at transplant with an HLA-compatible related or unrelated donor, between myeloablative conditioning with fractionated 12 Gy total body irradiation plus etoposide and chemoconditioning with fludarabine, thiotepa and either busulfan or treosulfan. The trial's own stated rationale was that total body irradiation is efficacious but long-term side effects are concerning. Between April 2013 and December 2018, 417 patients were randomised, 212 to total body irradiation and 201 to chemoconditioning, and the stopping rule was applied on 31 March 2019 because chemoconditioning was significantly inferior.\n\nThat result is the honest centre of this record. The late costs of total body irradiation are real and are documented throughout this file: cataract, second solid cancers with a ninefold relative risk in those irradiated under 30, renal impairment, thyroid and gonadal failure, altered body composition and reduced growth. The trial that tested removing it in the population where it is most used in children found that doing so cost survival. Conditioning choice is therefore a genuine trade-off, made case by case, and a reader should expect their team to be able to explain which way they have made it and why, rather than to present either option as free.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Total_body_irradiation","links":[{"label":"Hou et al., Fertility assessment in long-term young female survivors with hematological disease after allogeneic hematopoietic cell transplantation (Ann Hematol 2025)","url":"https://doi.org/10.1007/s00277-025-06275-4"},{"label":"Retrospective study of fertility in female patients with hematological diseases after allogeneic hematopoietic stem cell transplantation (Zhonghua Xue Ye Xue Za Zhi 2025)","url":"https://doi.org/10.3760/cma.j.cn121090-20250630-00307"},{"label":"Reproductive health assessment and reports of fertility counseling in pediatric and adolescent patients with sickle cell disease after hematopoietic cell transplantation (Transplant Cell Ther 2024)","url":"https://doi.org/10.1016/j.jtct.2024.06.029"},{"label":"Peters et al., Total body irradiation or chemotherapy conditioning in childhood ALL: a multinational, randomized, noninferiority phase III study, FORUM (JCO 2021)","url":"https://doi.org/10.1200/JCO.20.02529"},{"label":"Majhail et al., Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation (Biol Blood Marrow Transplant 2012)","url":"https://doi.org/10.1016/j.bbmt.2011.12.519"},{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"}],"tags":["rejuvenation","survivorship","transplant","fertility","late-effects","radiation"],"related":["rejuv-tx-endocrine-and-cardiometabolic","rejuv-tx-late-effects-overview","ovarian-function-after-chemotherapy","menopause-after-cancer-treatment","testosterone-after-cancer-treatment","sexual-function-after-cancer","rejuv-tx-quality-of-life"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["fertility-preservation","total-body-irradiation","allogeneic-hsct","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","conditioning-regimen","quality-of-life"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Oocytes are a non-renewing population and spermatogonial stem cells are highly radiosensitive, so the gonadal effect of myeloablative conditioning is a one-time depletion rather than a reversible suppression. Growth plate chondrocytes and the hypothalamic-pituitary axis are similarly sensitive and similarly non-renewing in effect, which is why height loss after irradiation in childhood is permanent. Preservation therefore has to precede the exposure; nothing afterwards restores the pool.","strengths":["Preservation options exist for most situations and most can be completed in about two weeks","Hormone replacement restores menstruation in nearly all women who take it and treats the downstream bone and cardiovascular consequences","Births after transplant using cryopreserved gametes are documented","Growth hormone deficiency after irradiation is treatable and growth monitoring is in the screening recommendations"],"limitations":["Most people lose natural fertility; in published series 86 to 94 per cent of young women after transplant for acute leukaemia had ovarian failure or amenorrhoea","Opportunities are lost if the conversation happens after conditioning starts","A large minority of patients and families report never being told about the risk","Replacing total body irradiation with chemoconditioning in childhood ALL was significantly inferior in the randomised FORUM trial","The fertility series cited are single-centre and from one country, so the exact percentages do not generalise"]},"route":"/technologies/rejuv-tx-fertility-and-growth/","neighbours":{"technology":[{"id":"rejuv-tx-what-to-ask-for","kind":"technology","name":"After a transplant or cell therapy: what to ask for","route":"/technologies/rejuv-tx-what-to-ask-for/"},{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"rejuv-tx-endocrine-and-cardiometabolic","kind":"technology","name":"Hormones, metabolism and the heart after transplant","route":"/technologies/rejuv-tx-endocrine-and-cardiometabolic/"},{"id":"rejuv-tx-late-effects-overview","kind":"technology","name":"Late effects after a stem cell transplant","route":"/technologies/rejuv-tx-late-effects-overview/"},{"id":"menopause-after-cancer-treatment","kind":"technology","name":"Menopause brought on by cancer treatment, and the options for it","route":"/technologies/menopause-after-cancer-treatment/"},{"id":"fertility-preservation","kind":"technology","name":"Oncofertility and fertility preservation","route":"/technologies/fertility-preservation/"},{"id":"ovarian-function-after-chemotherapy","kind":"technology","name":"Ovarian function after chemotherapy: who recovers, and when","route":"/technologies/ovarian-function-after-chemotherapy/"},{"id":"rejuv-tx-quality-of-life","kind":"technology","name":"Quality of life after transplant and cell therapy","route":"/technologies/rejuv-tx-quality-of-life/"},{"id":"sexual-function-after-cancer","kind":"technology","name":"Sexual function and intimacy after cancer, for both sexes","route":"/technologies/sexual-function-after-cancer/"},{"id":"survivorship-care-plan","kind":"technology","name":"Survivorship care and late-effects surveillance","route":"/technologies/survivorship-care-plan/"},{"id":"testosterone-after-cancer-treatment","kind":"technology","name":"Testosterone after cancer treatment in men","route":"/technologies/testosterone-after-cancer-treatment/"},{"id":"total-body-irradiation","kind":"technology","name":"Total body and total marrow irradiation","route":"/technologies/total-body-irradiation/"},{"id":"rejuv-access-fertility-preservation","kind":"technology","name":"Who gets told about fertility before treatment, and who does not","route":"/technologies/rejuv-access-fertility-preservation/"}],"section":[{"id":"rejuvenation","kind":"section","name":"Recovery & Rejuvenation","route":"/fronts/rejuvenation/"},{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"}],"term":[{"id":"conditioning-regimen","kind":"term","name":"Conditioning regimen (myeloablative, reduced-intensity)","route":"/terms/conditioning-regimen/"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"},{"id":"quality-of-life","kind":"term","name":"Quality of life","route":"/terms/quality-of-life/"}],"bottleneck":[{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}]}}