O-275 Is there a case for ovarian tissue cryopreservation in young girls and Turner syndrome patients?

Abstract

Abstract The development of new cancer drugs and drug combinations has led to a dramatic increase in the survival rates of prepubertal and postpubertal girls undergoing myeloablative treatment for malignant or non-malignant diseases. This includes girls who will receive high doses of alkylating agents, total body irradiation, or high radiation doses to the craniospinal, abdominal or pelvic area. Chemotherapy is also used as a conditioning regimen before hematopoietic stem cell transplantation for treatment of, for example, beta thalassaemia or homozygous sickle-cell anaemia. The corollary of improved treatment outcomes of childhood diseases is that many survivors are now at risk of multi-faceted, chronic morbidity, impaired quality-of-life and psychosocial problems. Depending on the nature and duration of their treatment some, but not all, young patients facing fertility threatening diagnosis and treatments will have an increased risk of adverse pregnancy outcomes and premature ovarian insufficiency (POI) as their future fertile potential will be defined by the number of follicles remaining in their ovaries following completion of their chemotherapy/radiotherapy. While a fully functioning hypothalamic-pituitary-ovarian axis and uterus are vital to the reproductive potential of adult females, Ovarian tissue cryopreservation (OTC) is now being used to safeguard the future fertility of prepubertal and adolescent girls and young women undergoing treatments that have a high risk of causing POI. OTC is increasingly advocated for young girls receiving an early diagnosis of the most common sex chromosome abnormality- Turner Syndrome (TS) who have a high risk of POI. In theory the ovaries of girls, including TS patients with an adequate ovarian reserve, are well suited to OTC as their ovaries contain high numbers primordial follicles which can be used to preserve future fertility. Ovarian tissue can be removed laparoscopically and early staged follicles cryopreserved in situ within slices of cortex. The operative approaches used for tissue removal from paediatric and adolescent patients are variable and invasive and are dependent on patient age, health and ovarian reserve at the time of tissue recovery. Extensive research has shown that ovarian cryopreservation techniques are robust and that experienced practitioners can achieve high levels of survival of both the ovarian stroma and follicle compartments post thaw. Cryobanked ovarian cortex collected from prepubertal and postpubertal girls has been shown to function normally and support fertility, pregnancy to term and the birth of healthy babies following orthotopic autografting in adulthood. Regardless of patient age at tissue preservation, autografting of frozen-thawed ovarian cortex at either the site of the retained ovary or into the peritoneal cavity results in an immediate and significant follicle loss due to ischaemia and accelerated apoptosis. Those primordial follicles that survive graft revascularization have been shown to have the capacity to grow to preovulatory stages, to reinstate hormonal function and to undergo ovulation and restore natural fertility. Alternatively, follicle growth can be induced in autografted tissue by controlled ovarian stimulation before oocyte harvest for insemination in vitro using assisted reproductive technologies. Graft functional longevity remains variable between patients and may extend from months to years. Alternative methods for fertility restoration such as the complete in vitro growth and maturation of oocytes and the construction of artificial ovaries remain unproven in humans. While OTC can be recommended for young girls at high risk of developing ovarian insufficiency for genetic reasons or following high dose chemotherapy and/or irradiation, to date very few young patients with stored ovarian tissue have used their tissue for fertility restoration. OTC therefore remains experimental and further research is needed to establish the risks, benefits, efficacy, safety and ethical and clinical frameworks for offering fertility preservation to girls during childhood and adolescence and to girls with TS.