Fertility Potential and Gonadal Function in Survivors of Reduced Intensity HCT.

BACKGROUND

Use of reduced intensity conditioning (RIC) regimens has increased to minimize hematopoietic cell transplantation (HCT) end-organ toxicity, including gonadal toxicity.

OBJECTIVE

We aimed to describe the incidence of fertility potential and gonadal function impairment in adolescent and young adult survivors of HCT and determine risk factors (including conditioning intensity) for impairment.

STUDY DESIGN

We performed a multi-institutional, international, retrospective cohort study of patients ages 10-40 who underwent first allogeneic HCT prior to December 1, 2019, and who are alive, in remission, and available for follow-up at one to two years post-HCT. For females, an AMH level of ≥0.5 ng/mL defined preserved fertility potential; an AMH level of ≥0.03 ng/mL was considered detectible. Gonadal failure was defined for females as an elevated FSH >30 mIU/mL with estradiol (E2) <17 pg/mL, or current use of hormone replacement therapy (regardless of specific indication/ intent). For males, gonadal failure was defined as FSH >10.4 mIU/mL, or current use of hormone replacement therapy.

RESULTS

A total of 326 patients (147 female) were available for analysis from 17 programs (13 pediatric, 4 adult). At 1-2 years post-HCT, 114 (77.6%) females had FSH and E2 levels, and 71 (48.3%) had AMH levels available; FSH levels were reported for 125 (69.8%) males. Nearly all female HCT recipients had very low levels of AMH. One of 45 MAC (2.2%) vs. four of 26 RIC (15.4%), (p=0.06) had an AMH ≥0.5 ng/m, and eight of 45 MAC (17.8%) vs. 12 of 26 RIC (46.2%), (p=0.015) had a detectible AMH. Total Body Irradiation (TBI) dose and cyclophosphamide equivalent dose (CED) were not associated with detectible AMH. The incidence of female gonadal hormone failure was 55.3%. In univariate analysis, older age at HCT was associated with greater likelihood of gonadal failure (median age: 17.6 vs. 13.9, p<0.0001), whereas conditioning intensity (RIC vs. MAC), TBI, chronic Graft-versus-Host Disease requiring systemic therapy, and CED were not significantly associated with gonadal function. In multivariable analysis, age remained statistically significant (odds ratio 1.11 (95% CI 1.03-1.22) for each year increase, p=0.012), Forty-four percent of males had gonadal failure. In univariate analysis, older age (median 16.2 vs. 14.4 years, p=0.0005), and TBI dose (p=0.002) were both associated with gonadal failure, whereas conditioning intensity (RIC vs. MAC, p=0.06), and CED (p=0.07) were not statistically significant. In multivariable analysis age (odds ratio 1.16 (95% CI 1.06-1.27) for each year increase, p=0.0016) and TBI ≥600 cGy (odds ratio 6.23 (95% CI 2.21-19.15), p=0.0008) remained significantly associated with gonadal failure.

CONCLUSIONS

RIC does not significantly mitigate the risk for gonadal failure in females or males. Age at HCT and, specifically in males, TBI use, seem to be independent predictors of posttransplant gonadal function and fertility status. All patients should receive pre-HCT infertility counseling and be offered appropriate fertility preservation options and be screened post-HCT for gonadal failure.

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no potential conflicts of interest related to this work.