Background: Bone marrow transplantation (BMTx) involves pre-conditioning regimens that compromise fertility Delayed puberty and hypogonadism are common in children with beta thalassemia major, due to chronic disease and transfusion requirements, due to iron overload in endocrine glands.
Objective and hypotheses: Pubertal induction using hCG and FSH prior to gonadotoxic conditioning before BMTx should result in spermatogenesis sufficient to store sperm. We aimed to induce puberty and spermatogenesis, over a short time of 69 months before planned BMTx.
Methods: After explanation and parental consent, a prepubertal 13 year old boy with beta thalassemia major, height 151.9 cm (25 th centile), mid-parental expectation (90 th centile) was administered human chorionic gonadotropin (hCG) 500IU x2/week by subcutaneous injection, increased to 1000IU x2/week after 3 months. When serum testosterone rose to 11.9 nmol/l, follicle stimulating hormone (FSH) 150IU x3/week was added, to induce spermatogenesis, increased after 3 months to 300IU x3/week.
Results: Pubertal progress was mildly accelerated, height 169 cm, gain of 17.1 cm over 10 months. Adult virilisation with 20ml testes bilaterally occurred, with serum testosterone 17.6 nmol/L inhibin B 135 ng/L(50350). Semen collection, 9 months after commencing FSH, demonstrated 0.51.8 ×106/ml in three samples. Cryopreservation of 11 straws was undertaken. Four months after semen collection he underwent BMTx, preceded by Busulphan conditioning.
Discussion: This report provides the first evidence of feasibility of inducing puberty and spermatogenesis adequate for future fertility, in a prepubertal adolescent male, prior to BMTx. Unlike transplant performed in the setting of malignancy where time is extremely limited, elective transplant for non-malignant conditions may in some cases be postponed for a reasonable period to permit the possibility of pubertal induction and sperm retrieval. Fertility preservation in this case is assured. In the setting of chronic disease mild loss of final height may occur.
Conclusion: This option should be considered in future, for other adolescent males, prior to gonadotoxic treatments.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology