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Predictors of decision to pursue fertility preservation prior to gonadotoxic therapy in male pediatric, adolescent, and young adult patients
Abbey Riazzi, MSPAS, PA-C, Megan Sax, MD, Elizabeth Spitznagel, MSN, APRN, CPNP, Marion Schulte, RN, MHSA, Brycen Ferrara, BS, CRC II, Olivia Frias, MSN, RN III, CNL, Brian VanderBrink, MD, Paul Noh, MD, Bob DeFoor, Jr., MD, MPH, Eugene Minevich, MD, Pramod Reddy, MD, Karen Burns, MD, Julie Rios, MD, Andrew Strine, MD.
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

BACKGROUND:
Many therapies for childhood cancer as well as a variety of hematologic diseases and immunodeficiencies are gonadotoxic with the potential for permanent azoospermia. With an improving survival due to the advent of more effective multimodal therapies, the late effects on fertility have become increasing important. However, a paucity of evidence is available on the factors that influence the decision to pursue fertility preservation (FP) prior to gonadotoxic therapy in male pediatric, adolescent, and young adult patients.
METHODS:
A retrospective cohort study was performed for male patients in the Comprehensive Fertility Care and Preservation Program registry between September 2013 and October 2018. All male patients who received a consultation were included for analysis. The risk assessment was based on the cumulative cyclophosphamide equivalent dose and stratified into low (<20% risk of permanent azoospermia), intermediate (20-80%), and high (>80%) risk. Demographic and clinical data were compared between those who did and did not pursue an option for FP. A multivariate logistic regression model was fitted to determine the predictors of the decision to pursue FP.
RESULTS:
Of 471 consultations, 235 (49.9%) patients were eligible for FP during the study period. A total of 102 (43.4%) patients pursued an option for FP, including sperm cryopreservation in 73 patients and testicular tissue cryopreservation (TTC) in 29 patients. Neither the proportion of eligible patients at 56.1% (p=0.38) nor the patients pursuing an option for FP at 45.3% (p=0.85) significantly changed after IRB-approval of TTC in April 2016. Demographic and clinical data are included in the Table. A pre-pubertal stage of development (OR 0.04, p<0.001), a private insurance (OR 5.88, p=0.03), an intermediate-risk assessment (OR 7.60, p=0.003), a high-risk assessment (OR 6.76, p=0.005), and the care team (p<0.001) remained significant predictors of the decision to pursue FP in the multivariate logistic regression model.
CONCLUSIONS:
The stage of pubertal development, type of insurance, risk assessment, and care team influenced the decision to pursue FP prior to gonadotoxic therapy in male pediatric, adolescent, and young adult patients. Further research is needed to better characterize the barriers to FP in this population.

Fertility Preservation (n=102)No Fertility Preservation (n=133)p value
Age in years, median (IQR)15.5 (12.6-17.6)10.8 (2.8-16.3)<0.001
Pubertal development, n (%)
Pre-pubertal
Peri- or post-pubertal
29 (28.4)
73 (71.6)
80 (60.2)
53 (39.8)
<0.001
Race, n (%)
White
Middle Eastern
Black
Other
Refused or unknown
69 (67.6)
17 (16.7)
8 (7.8)
6 (5.9)
2 (2.0)
87 (65.4)
20 (15.1)
14 (10.5)
10 (7.5)
2 (1.5)
0.93
Primary language, n (%)
English
Other
85 (83.3)
17 (16.7)
111 (83.5)
22 (16.5)
1.00
Religion, n (%)
Christian
Muslim
Other
Refused or unknown
47 (46.1)
18 (17.6)
1 (1.0)
36 (35.3)
61 (45.9)
22 (16.5)
1 (0.8)
49 (36.8)
0.99
Insurance, n (%)
Private
Public
International
None or self pay
66 (64.7)
18 (17.6)
16 (15.7)
2 (2.0)
61 (45.9)
46 (34.6)
20 (15.0)
6 (4.5)
0.01
Prior treatment, n (%)14 (13.7)25 (18.8)0.38
Risk assessment, n (%)
Low
Intermediate
High
None
8 (7.8)
22 (21.6)
61 (59.8)
11 (10.8)
20 (15.1)
12 (9.0)
93 (69.9)
8 (6.0)
0.01
Care team, n (%)
Bone marrow transplant
Neuro-oncology
Leukemia/Lymphoma
Solid cancer
Other
35 (34.3)
7 (6.9)
24 (23.5)
33 (32.4)
3 (2.9)
62 (46.6)
14 (10.5)
28 (21.1)
29 (21.8)
0 (0.0)
0.04

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