Optimizing the process of fertility preservation in pediatric female cancer patients - a multidisciplinary program

Abstract

Background: Current evidence indicates sub-optimal incidence of fertility preservation (FP) in eligible patients. We present herein our designated multidisciplinary program for FP in pediatric and adolescent population and present our data on FP in female patients.

Methods: Pediatric patients (age 0-18) who were candidate for highly gonadotoxic treatments were referred to FP program for a multidisciplinary discussion and gonadal risk-assessment followed by either oocyte cryopreservation or ovarian cryopreservation (OCP) for female patients, and sperm banking for male patients. The OCP protocol consists of aspiration of oocytes from small antral follicles and in-vitro maturation followed by cryopreservation, as well as ovarian tissue cryopreservation.

Results: The establishment of a designated FP program resulted in a significant increase in referral and subsequent FP procedures of all eligible patients. Sixty-two female patients were referred for FP discussion during a period of 36 months; 41 underwent OCP; 11 underwent oocyte cryopreservation and six were declined due to parental decision. The median age was 13.2y (range 18 months-18y). Thirty-two (51.6 %) were chemotherapy-naïve. Seventeen patients (27 %) had sarcoma, 16 patients (26 %) had acute leukemia. The mean number of mature oocytes that were eventually vitrified was significantly higher in chemotherapy-naïve patients compared with chemotherapy-exposed patients (mean 12 oocytes (1-42) versus 2 (0-7)).

Conclusion: Multidisciplinary programs that encompass experts of all relevant fields, skilled laboratory resources and a facilitated path appear to maximize the yield. We observed a considerable higher referral rates following launching a designated program and earlier OCP in chemo-naïve patients that culminated in a better fertility preservation procedure.

Keywords: Fertility preservation; Ovarian cryopreservation; Pediatric cancer patients.

Fig. 1

FP options for prepubertal girls and pubertal adolescents. a Current evidence for ovarian cryopreservation. b Schematic representation of in vitro oocyte maturation (IVM) and subsequent cryopreservation. c Ovulation induction and oocyte retrieval and cryopreservation

Fig. 2

referral algorithm Oncofertility program at RMC. Team is comprised by REI, Oncologist (moderator), Psychologist. The lower part represents the components of the prospective study for longitudinal evaluation of reproductive outcomes in this cohort

Fig. 3

Characteristics of referred patients (a) Patient distribution according to cancer type (b) Patient distribution according to therapeutic protocol. Abbreviations: HL – Hodgkin’s lymphoma; AML – acute myeloid leukemia; ALL – acute lymphocytic leukemia; STS – soft tissue sarcoma; CNS – central nervous system; BMT – bone marrow transplantation TBI – total body irradiation, XRT – irradiation

Fig. 4

Reproductive outcomes (a) Small antral follicles - distribution according to prior chemotherapy exposure (naïve, recent (<1 year), prior chemotherapy (in case of cancer recurrence; >1y)). b In Vitro matured (frozen) oocytes; distribution according to prior chemotherapy exposure

Fig. 5

shifting paradigms – referral rate of chemo-naïve patients before and after initiation of a designated program. Bone tumors (Ewing sarcoma and osteosarcoma), RMS - Rhabdomyosarcoma