Introduction
Infertility secondary to chemotherapy, radiation therapy, and/or myeloablative conditioning regimen prior to hematopoietic stem cell transplantation (HSCT) is an important cause of morbidity and psychosocial distress among pediatric cancer patients [1]. Although there are several options for fertility preservation, they are often overlooked and deemed less important than other therapy related late effects [2]. Infertility is one of the primary concerns of cancer survivors who report symptoms of post-traumatic stress disorder (PTSD) related to infertility as long as 10 years post therapy [3]. Therefore, it is essential for the treating providers to discuss infertility risk and fertility preservation options with all female and male patients undergoing gonadotoxic therapy, and their families, before treatment starts [4].
Alkylating chemotherapy agents, such as cyclophosphamide, present the greatest risk of infertility as determined by the cyclophosphamide equivalent dose (CED). Additionally, dose dependent radiation therapy to the ovaries or testes, gonadectomy and myeloablative conditioning regimens (e.g., Busulfan) for HSCT present another significant fertility risk [5]. Meacham et al recently developed a standardized risk assessment for gonadal insufficiency and infertility secondary to treatment in children, adolescents, and young adults with cancer compared to the general population [5].
Fertility preservation options for males include sperm banking, testicular sperm extraction (TESE) and testicular tissue cryopreservation (TTC). Sperm banking is only available for post-pubertal males and must be completed before any therapy is started, otherwise the semen is only to be used as last resort due to potential effects on DNA[6]. TESE is an option for post-pubertal males who cannot produce a semen sample[6], and TTC is the only option available for pre-pubertal males undergoing gonadotoxic therapy, and it is still considered experimental at this time [7].
Fertility preservation options for females include oocyte and embryo cryopreservation, ovarian tissue cryopreservation (OTC) and ovarian transposition for those undergoing pelvic radiation therapy [8]. Oocyte and embryo cryopreservation are only available for post-pubertal females, and embryo cryopreservation requires the availability of sperm, which is not feasible for many teenagers and young adults. OTC is the only option available for pre-pubertal females undergoing gonadotoxic therapy, and based on recent American Society of Reproductive Medicine (ASRM) practice committee opinion, it is no longer considered experimental [9]. Additionally, the 2019 ASRM guidelines include general recommendations on fertility preservation options for patients undergoing gonadotoxic therapy[9],