FEMALE FERTILITY PRESERVATON OPTIONS Female Fertility Option Standard

FEMALE FERTILITY PRESERVATON OPTIONS

Female Fertility Option • Standard of Care Options • Oocyte / Embryo Cryopreservation • Ovarian Transposition • Experimental Options • Gn. RH Analogues • Ovarian Cryopreservation

STANDARD OF CARE OPTIONS

Oocyte & Embryo Cryopreservation Consideration in Pediatric & Adolescent Patients • Standard of Care options in post-pubertal female patients • Oocyte cryopreservation non-experimental (ASRM 2012) • Controlled ovarian stimulation multiple mature oocytes • Success rates published by clinic • Society for Assisted Reproductive Technologies • Average: 33 -52% live birth rates • Limited adolescent and oncology specific data • Barriers: Time/delay in treatment, cost/insurance coverage, concern for procedural technique or side effects • Consideration: Adolescent friendly alterations Mature oocyte cryopreservation: A Guideline. Fertil Steril 2013; 99: 37– 43

Ovarian Transposition • Pelvic or abdominal radiation with significant risk of amenorrhea and subsequent infertility. • greater than 15 Gy in prepubertal girls • greater than 10 Gy in postpubertal girls • Surgically move ovaries out of the radiation field • Success rates • • 50 -90% reduction in radiation to the ovary 30 -50% maintenance of ovarian function Unknown fertility preservation success Not well study in pediatric population Estes S End Met 2015, https: //www. cincinnatichildrens. org/service/f/fertility-preservation/females

EXPERIMENTAL OPTIONS

Gn. RH Analogues • Mimic pre-pubertal “quiescent” ovary • Problems with early study design • More recent studies improve design • 3 show decreased amenorrhea • 3 show no protection of ovarian reserve (2 stopped earlier) • 2013 ASCO Guidelines: Insufficient evidence • POEMS Trial (2015) • Breast Cancer + Goserelin • Reduction in ovarian failure (p = 0. 04) • Increased odds ratio for pregnancy (p = 0. 03) Levine J Children 2014, Loren AW et al J Clin Oncol 2013, Moore HCF et al J Clin Onc 2014.

Ovarian Tissue Cryopreservation Jadoul P et al. Hum. Reprod. Update 2010; 16: 617 -630 Ovarian Tissue Cryopreservation: A Committee Opinion. Fertil Steril. 2014; 101: 1237– 43

Orthotopic Transplantation Ovarian Fossa Donnez et al. Frontiers in Bioscience 2012, Donnez et al. Fert Steril 2012 Contralateral Ovary Donnez J et al. Hum. Reprod. Update 2006; 12: 519 -535

Donnes et al. , 2013, 2016; Dittrich et al. , 2015; Jensen et al. , 2015; Meirow et al. , Van der en et al. , 2016

CCHMC OTC Protocols • Females 1 month to 41 years of age • Undergo surgery, chemotherapy, drug treatment, and/or radiation for the • treatment or prevention of a medical condition or Purposely left broad malignancy expected to result in permanent and complete loss of • No restrictions based on risk subsequent ovarian function • Or, haveassessment a medical condition or malignancy that requires removal of all or part of one both ovaries. • Allows fororcase by case evaluation • Is not a candidate for or chooses not to utilize embryo or oocyte banking. • Serum FSH levels ≤ 20 m. IU/ml.

OTC at CCHMC N = 52 Age ranged from 0. 6 years to 33. 2 years old Median age 10. 7 years old

OTC at CCHMC N = 52 Diagnosis Types Malignancy Infertility Risk 25 Solids 18 Liquids 2 High 47 Intermediate 5 Low 0 Neuro-Onc 5 Menarchal Status Hematologic Disorder 20 Premenarchal 34 Immune Deficiency 4 Post-menarchal 18 Metabolic Disorder 1 Time < 2 weeks 11 Other 2 Time > 2 weeks 7 Time Available Treatment Chemo Alone 10 < 1 week 8 Chemo + Radiation 11 1 -2 weeks 15 Bone Marrow Transplant 31 2 -6 weeks 19 > 6 weeks 10 Myeloablative 17 RIC 14 Benoit J, Hoefgen HR, et al. , Publication Pending (n= 52)