Comparable infertility risk across HCT conditioning regimens supports thorough fertility preservation counseling

February 2024

Given the high risk of infertility associated with hematopoietic cell transplant (HCT), this study evaluated the fertility potential and gonadal function in adolescent and young adult survivors of HCT, focusing on the differences between reduced-intensity conditioning (RIC) and myeloablative conditioning (MAC) regimens. Researchers found no significant differences in fertility outcomes between RIC and MAC regimens for HCT patients, emphasizing the importance of thorough education and counseling on fertility preservation options before HCT.

Download a PDF to the study highlights and citation here

Background

HCT is a life-saving treatment for various malignant and non-malignant diseases, but it comes with significant risks, including gonadal failure and infertility. These side effects can severely impact quality of life for survivors. As a result, understanding the risk factors and outcomes related to fertility post-HCT is crucial. The shift towards using RIC regimens over MAC has been driven by the desire to reduce end-organ toxicity, including gonadal toxicity, in HCT patients. However, the impact of RIC on fertility preservation compared to MAC is not well understood.

Methods

This multi-institutional, international, retrospective cohort study was conducted to assess the incidence of impaired fertility and gonadal function in HCT survivors and identify key risk factors, such as conditioning intensity, that may contribute to these outcomes.

Researchers analyzed data from 17 programs across 15 institutions in the United States and Brazil. The study included 326 patients aged 10-40 years who underwent their first allogeneic HCT before Dec. 1, 2019. Participants were selected based on their survival, remission status and availability for follow-up 1-2 years post-HCT. Exclusion criteria included previous bilateral orchiectomy/oophorectomy, pre-HCT gonadal failure, radiotherapy to the gonads outside of conditioning and certain diagnoses like Fanconi anemia. Patients who required additional conditioning for graft failure within the first year post-HCT were also excluded.

Results

Of the study participants, 54% had a malignant indication for HCT, 26% were racially/ethnically diverse and 20% were of Hispanic ethnicity. Overall, 63% of patients received MAC compared to 37% RIC, and 46% underwent total body irradiation (TBI). No significant difference in fertility potential or toxicity was observed between RIC and MAC regimens in male or female patients.

Of 114 evaluable female patients, 55.3% experienced gonadal failure. Older age at the time of HCT was a significant risk factor, while conditioning intensity, TBI and other factors were not.

Of 125 evaluable male patients, 44% experienced gonadal failure. Like females, older age at HCT significantly increased the risk. Additionally, higher doses of TBI significantly raised the likelihood of gonadal failure, with standard doses (>600 cGy) posing a much greater risk compared to no TBI. See the Figure below.

Key takeaways

This study found no significant difference in fertility outcomes between RIC and MAC regimens for HCT patients, suggesting that RIC does not offer a protective effect against gonadal failure. These findings emphasize the need for thorough education and counseling on fertility preservation options before HCT, especially given the high risk of infertility associated with the treatment. The study also underscores the importance of ongoing screening for gonadal failure in long-term survivors. Given that older age at the time of HCT is a significant risk factor for infertility, these insights can guide family planning and treatment decisions for patients considering HCT.

Figure

This figure shows male gonadal failure based on TBI dosage.

Rotz S, et al., published in Transplantation and Cellular Therapy.