# Hodgkin Lymphoma—The Effect of Chemotherapy on Gonadal Function and Fertility Is Strongly Related to the Treatment Regimen, Age, and Sex: A Systematic Review and Meta-Analysis

## TL;DR

This study shows that chemotherapy for Hodgkin lymphoma affects fertility differently based on treatment type, age, and sex, guiding personalized fertility counseling.

## Contribution

The paper provides the first comprehensive meta-analysis of chemotherapy-induced infertility in Hodgkin lymphoma patients, stratified by regimen, age, and sex.

## Key findings

- Presumed infertility rates are 21% in women and 45% in men after Hodgkin lymphoma chemotherapy.
- Regimens like BEACOPP have high infertility risks (38% in women, 81% in men), while ABVD has much lower risks (6% in both sexes).
- Male adolescents treated for Hodgkin lymphoma face particularly high infertility risks (67%).

## Abstract

Hodgkin lymphoma (HL) mainly affects people during their reproductive years, making fertility an important part of survivorship. Although cure rates are high, chemotherapy can impair gonadal function, with the extent of damage depending on the specific regimens used, as well as on age and sex. To provide clearer, evidence-based counselling, we systematically reviewed studies published since 2000 and combined data from more than 7000 patients. Overall, the likelihood of presumed infertility after treatment was approximately 21% in adult women and 45% in adult men. Infertility risk varies widely by regimen: it is low after ABVD but substantially higher after regimens containing alkylating agents. Men are generally at greater risk than women, and boys treated during childhood/adolescence show particularly high vulnerability. These findings highlight the importance of personalized fertility counselling and help determine when fertility preservation before treatment is essential and careful post-treatment assessment may be sufficient.

Background/Objectives: Hodgkin lymphoma (HL) primarily affects individuals of reproductive age, making gonadal dysfunction after chemotherapy a critical survivorship concern. While fertility preservation options including gamete and gonadal tissue cryopreservation are available before treatment, evidence-based counseling requires regimen-specific risk estimates accounting for patient age and sex. Therefore, a meta-analysis was performed to assess presumed infertility in HL patients, stratified by chemotherapy regimen, age, and sex. Methods: This systematic review and meta-analysis, conducted within the FertiTOX project, included studies published between 2000 and February 2024. Eligible studies reported gonadal function outcomes ≥ 1 year after chemotherapy, excluding patients who received pelvic radiotherapy or stem cell transplantation, or had recurrent disease. Presumed infertility was defined by surrogate markers, including amenorrhea, premature ovarian failure, or abnormal hormonal levels in women, and azoospermia, oligozoospermia, or abnormal hormonal levels in men. Results: Of 2376 screened studies, 50 were included (meta-analysis: 43 studies; 5564 female and 1631 male patients). Overall presumed infertility prevalence was 21% in women (95% CI: 0.14–0.29) and 45% in men (95% CI: 0.29–0.62). The highest prevalence occurred after BEACOPP (women 38%; men 81%), while ABVD was associated with the lowest (6% each in women and men). Childhood/adolescent HL treatment resulted in lower prevalence in women (8%) but remained high in men (67%). Conclusions: Fertility risk depends on regimen, age, and sex, requiring tailored counseling. For female children/adolescents and all patients receiving ABVD, post-treatment fertility evaluation and treatment may suffice. However, pre-treatment fertility preservation is strongly recommended for male adolescents and patients receiving other regimens.