ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Bone Marrow Transplant. 2020 Apr 24. doi: 10.1038/s41409-020-0914-5. Epub ahead of print. a.leiper@nhs.net

Anti-Müllerian hormone (AMH), secreted by granulosa cells of growing pre- and early antral ovarian follicles, reflects the reserve of primordial ovarian follicles at any time from birth to menopause. Serum AMH levels are low during childhood, increase to a plateau in the mid-twenties and progressively decline to the menopause. lnhibin B is produced by Sertoli cells, serum levels surge during puberty and then plateau. Inhibin B measurement is considered a suitable surrogate marker of spermatogenesis, even if cannot replace semen analysis. Low AMH and lnhibin B levels reflect the entity of gonadal damage related to chemotherapy and represent promising tools to predict infertility in childhood cancer survivors (CCS).

In this study, serum levels of AMH and inhibin B were analysed to assess fertility potential in survivors of childhood hematopoietic stem cell transplantation (HSCT) after 3 different chemotherapy-based conditioning treatments. Group A received a treosulfan-based low-toxicity regimen; Group B had reduced-intensity regimen based on fludarabine/melphalan (Flu-Mel) and Group C received a busulphan/cyclophosphamide (Bu-Cy) myelo-ablative regimen.

In females, AMH levels expressed as mean standard deviation scores (SDS) were below zero in all groups, but were significantly higher after treosulfan (group A) and Flu-Mel (group B) than after Bu-Cy (group C). Gonadotropin levels were normal in group A, and elevated in group B and C.

In males, gonadotrophins were normal for age in all groups, but FSH levels were significantly higher in Group B, than in group C. Mean Inhibin B levels in boys were significantly higher in Group A than in Group B and C, with the Flu-Mel group showing the greatest impairment.

The treosulfan-based regimen is confirmed to be less gonadotoxic than myeloablative Bu-Cy in both sexes. Flu-Mel appears to be less gonadotoxic than Bu-Cy and is comparable to treosulfan in girls, while it is associated with the most severe damage in boys. Late recovery of spermatogenesis in the Bu-Cy myeloablative group may explain this sex difference. This study also confirms that AMH and inhibin B are more reliable than gonadotrophins in the early prediction of gonadal failure in patients treated with conditioning regimens.

References:

1. Slatter MA, Rao K, Abd Hamid IJ, Flood T, Abinun M, Hambleton S, et al. Treosulfan and fludarabine conditioning for hematopoietic stem cell transplantation in children with primary immunodeficiency: UK experience. Biol Blood Marrow Transpl. 2018;24:529–36.