Gonadal function in pediatric Fanconi anemia patients treated with hematopoietic stem cell transplant

Abstract

Gonadal dysfunction and reduced fertility are clinical manifestations well described in patients with Fanconi anemia (FA) and following hematopoietic stem cell transplantation (HSCT). It is difficult to differentiate gonadal dysfunction from the primary disease itself or from HSCT procedures. Therefore, it is important to manage expectations about gonadal failure and infertility for all patients with FA, regardless of HSCT status. We performed a retrospective analysis of 98 pediatric patients with FA who were transplanted between July 1990 to June 2020 to evaluate the incidence of gonadal dysfunction in female and male patients with FA. New onset premature ovarian insufficiency (POI) was diagnosed in a total of 30 (52.6%) patients. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were increased in patients diagnosed with POI. Anti-Mullerian Hormone (AMH) levels declined in POI patients after HSCT (r2 = 0.21, p = 0.001). Twenty (48.8%) male patients were diagnosed with testicular failure. FSH levels increased after HSCT even in patients without testicular failure (r2=0.17, p=0.005). Inhibin B levels decreased over time after HSCT in patients with testicular failure (r2 = 0.14, p = 0.001). These data indicate brisk decline in already impaired gonadal function in transplanted children with FA.

Fertility Preservation in Pediatric Age: Future Perspective among Andrological Diseases

“…After understanding all the fundamental passages of spermatogenesis and its regulation, it is possible to understand how various alterations created by external pathologies can affect the correct mechanism. Hormonal alterations will be the cause of the failure of Sertoli and Leydig cells to function, and alterations in temperature and the production of free radicals directly generated by stress on the testis will be the cause of the failure of spermatozoa to mature, and genetic alterations will be associated with more or less complete alterations in molecular regulatory mechanisms [ 2 , 3 , 4 , 5 , 6 , 7 ].…”

“…It is therefore essential to raise awareness around parents and doctors who care for pediatric patients suffering from cancer regarding the risks of infertility [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ].…”

“…Therefore, many patients are at risk for long-term side effects such as impaired pubertal development and impaired fertility, especially for testes disorders. In some cases, previous treatment or the disease itself may have caused spermatogonia loss [ 7 ].…”

“…Bone marrow failure is another represented group of benign conditions for which immature testicular tissue is banked. Many of these conditions require HSCT and, therefore, testicular failure [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ].…”

“…Any disease that can be related to hypogonadotropic hypogonadism, with a deficiency of hypothalamic/pituitary function, can result in a defect in spermatogenesis, failing stimulation with GnRH on the pituitary or gonadotropins on the testis. The consequence of this is the absence of hormonal stimulation on the testis related to spermatogenesis [ 3 , 4 , 5 , 6 , 7 ].…”