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Jill Davies

Jill Davies

Oxford University, UK

Title: Fertility cryopreservation in Oxford, UK

Biography

Biography: Jill Davies

Abstract

Late effects of cancer treatment may cause premature infertility in children and adolescent cancer survivors. Oxford applied for UK license for cryopreservation of ovarian and immature testicular tissue (ITT) for patients requiring gonadotoxic treatment. This required validation with animal/human studies, development of protocols, information, staff training, establishing costs/funding source. Oxford recruited first set of patients in 2013. Patients eligible for treatment intent is curative, cytoxicity high risk, age <40 years (females) and boys pre-pubertal. Patients consented prior to day of surgery. Ovarian tissue from 145 females, age 10 months – 39 years cryopreserved (14% with benign diagnosis), testicular tissue (ITT) from 31 boys, (0.9–13.6 years). Referrals from oncologists/hematologists and patients, most patients travel to Oxford for surgery scheduled to coincide with other interventions (minimizing risk of anesthesia). Right ovary procured using laparoscopic oophorectomy, wedge testicular biopsy procured via midline incision. Tissue bank technician collects tissue and dissects within cleanroom, producing ovarian cortical strips (1x1x5mm) containing primordial follicles or testicular segments (2x2x2 mm) containing spermatagonial stem cells. Histological evaluation reviews viability and presence of metastatic cells. Immature oocytes collected for in vitro maturation (IVM) and vitrified. Cryopreservation of ovarian tissue requires ethylene glycol, sucrose, human albumin serum, slow controlled freezing (manual seeding at 8ËšC) and vapor phase nitrogen storage. DMSO is used for ITT. Tissue is stored until the patient is cured and confirmed infertile. 86 live births following ovarian tissue transplantation was recorded. A live birth in ITT is successful in animal studies only. Patients with hematological malignancy will use vitrified oocytes (gametes are free from residual disease). For other females and ITT patients, tissue will be matured in vitro (IVM) to develop primordial follicles/spermatogenesis for use in conventional ART. Oxford University researchers currently are optimizing IVM techniques (three dimensional/organ culture studies). All details were registered in OTCP database. Service evaluation (interviews with patients/parents) confirms patients/parents understood risks/potential for fertility restoration. Setting up the Oxford service has been challenging due to evolving UK legislation. Referrals are from all UK centers.