ESPEYB20 7. Oncology and Chronic Disease Gonadal Function and Fertility Issues in Childhood Cancer Survivors (7 abstracts)
7.4. Reduced-intensity conditioning mitigates risk for primary ovarian insufficiency but does not decrease risk for infertility in pediatric and young adult survivors of hematopoietic stem cell transplantation
Bender JD , Oquendo-Del Toro H , Benoit J , Howell JC , Badia P , Davies SM , Grimley MS , Jodele S , Phillips C , Burns K , Marsh R , Nelson A , Wallace G , Dandoy CE , Pate A , Strine AC , Frias O , Breech L , Rose SR , Hoefgen H , Khandelwal P & Myers KC
jonathan.bender@cchmc.org Transplant Cell Ther. 2023 Feb;29(2):130.e1–130.e8.
Brief summary: This single-center, retrospective, cross-sectional study compared the prevalence of gonadal insufficiency and infertility among 58 pubertal, post pubertal and young adult survivors of hematopoietic stem cell Transplantation (HSCT), treated with conditioning regimens of different intensity.
Gonadal insufficiency or infertility affects almost all HSCT survivors who received a myeloablative conditioning (MAC) regimen. In recent years, reduced-intensity conditioning (RIC) regimens have been proposed and are increasingly used in medically fragile patients or in patients with nonmalignant diseases to limit the toxicities associated with HSCT.
In this study, females who received RIC showed a lower prevalence of primary ovarian insufficiency (0% versus 53%), although most females in the RIC (75%) and MAC (93%) groups had low levels of anti-Mullerian hormone (AMH), indicating an impaired follicular reserve. Male RIC recipients less frequently showed testicular failure (5% vs 25% of MAC recipients) and low Inhibin B levels (31% versus 67%), although these differences did not reach statistical significance. Almost all males who underwent semen analysis had azoospermia or oligospermia: 10/11 RIC recipients and 10/10 MAC recipients.
All patients undergoing HSCT should receive counseling about the high risk of gonadal toxicity, and efforts should be made to preserve their fertility before receiving cancer treatment. This study shows that RIC regimens reduce the risk of primary ovarian insufficiency, although both RIC and MAC conferred a significant risk of infertility in survivors of both sexes. The study reports the largest series of semen analyses in young recipients of RIC regimens – unfortunately, azoospermia or oligospermia was found in nearly all (91%) RIC survivors.
Study limitations include the lack of pre-HSCT data on gonadal function to identify patients with a pre-existing gonadal dysfunction, and LH and FSH measurements irrespective of the menstrual cycle in females. Moreover, the cross-sectional study design does not allow longitudinal assessment of gonadal function, given the possible recovery of both gonadal function and fertility many years after transplantation. To this end, the same working group is conducting a larger longitudinal study with a long follow-up, to draw more definitive conclusions about the different short- and long-term gonadotoxicity associated with MAC and RIC regimens.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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