ESPEYB21 9. Oncology and Chronic Disease Fertility Issues (9 abstracts)
9.5. Fertility potential and gonadal function in survivors of reduced-intensity hematopoietic stem cell transplantation
Rotz SJ , Hamilton BK , Wei W , Ahmed I , Winston SA , Ballard S , Bernard RJ , Carpenter P , Farhadfar N , Ferraro C , Friend BD , Gloude NJ , Hayashi RJ , Hoyle K , Jenssen K , Koo J , Lee CJ , Mariano L , Nawabit R , Ngwube A , Lalefar N , Phelan R , Perkins L , Rao A , Rayes A , Sandheinrich T , Stafford L , Tomlinson K , Whiteside S , Wiedl C & Myers K
rotzs@ccf.org Transplant Cell Ther. 2024 May; 30 (5):534.e1-534.e13. doi: 10.1016/j.jtct.2024.02.002. PMID: 38342136
Brief Summary: This multicenter, international, retrospective study evaluated fertility potential and gonadal function in 326 adolescent and young adult cancer survivors. Risk factors for impairment included hematopoietic stem cell transplantation (HCT) conditioning regimen (myeloablative conditioning, MAC vs reduced-intensity conditioning, RIC).
The prevalence of gonadal hormone failure in females was 55.3% (defined as FSH >30 mIU/mL with an estradiol <17 pg/mL or current use of hormone replacement therapy). Only 1/45 female recipients of MAC and 4/26 recipients of RIC had preserved fertility potential (AMH ≥0.5 ng/mL). Older age at HCT was associated with greater likelihood of gonadal failure, while conditioning intensity, total body irradiation (TBI), chronic graft-versus host disease (GVHD) requiring systemic therapy and cyclophosphamide equivalent dose (CED) were not associated with gonadal function. The incidence of gonadal failure in males was 44% (defined as FSH >10.4 mIU/mL or current use of hormone replacement therapy). Older age (median, 16.2 vs 14.4 years) and TBI dose were associated with gonadal failure, whereas conditioning intensity and CED were not significantly associated.
RIC regimens are increasingly used to decrease end-organ toxicity from HCT. However, the results here suggest that RIC does not substantially mitigate the risk for gonadal failure in either sex. More RIC recipients had detectable AMH levels and all 4 females with spontaneous pregnancy had a nonmalignant condition and received RIC, but these successes were infrequent.
Study limitations include the small number of patients with measured hormone levels and the short follow up (1 to 2 years post-HCT). It is possible that differences in AMH levels between RIC and MAC recipients might only emerge during a longer follow-up. The authors did not account for pubertal stage at the time of HCT, and therefore patients who remained prepubertal 1 to 2 years post-transplantation might have spuriously low FSH levels (despite substantial gonadal damage). Only 7 males had post-HCT semen analysis, which is the gold standard for assessing fertility in HCT male survivors. Further studies investigating the fertility outcomes of newer, specific conditioning regimens with reduced-toxicity (eg, treosulfan-based) are needed.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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