Clinical Report: Fertility Impact of Hematopoietic Stem Cell Transplantation

Overview

Hematopoietic stem cell transplantation (HSCT) is increasingly used for malignant and benign hematologic conditions, with improved survival rates. However, HSCT conditioning regimens carry a high risk of gonadal toxicity leading to infertility, with pregnancy rates post-HSCT reported below 5%. This systematic review and meta-analysis assess gonadal toxicity to guide fertility preservation counseling.

Background

HSCT is a curative or consolidative therapy for various hematologic malignancies and benign disorders. The number of HSCT procedures continues to rise, with 47,412 performed in Europe in 2021 and 5-year survival rates reaching up to 90% for some diseases. Despite improved outcomes, long-term complications such as infertility due to primary ovarian insufficiency or testicular failure remain significant concerns. Fertility preservation strategies are complex and vary depending on disease type, urgency of transplantation, and patient age.

Data Highlights

The systematic review included studies from 2000 onwards, focusing on fertility outcomes post-HSCT in both males and females with benign and malignant hematologic diseases. Quality assessment was performed using the Newcastle-Ottawa Scale. Fertility preservation options differ by patient demographics and disease urgency, with sperm freezing feasible before induction chemotherapy in males, while oocyte or ovarian tissue preservation is limited in females, especially prepubertal patients.

Key Findings

• HSCT conditioning regimens are highly gonadotoxic, frequently causing primary ovarian insufficiency or testicular failure.
• Pregnancy rates after HSCT are generally less than 5%, indicating significant infertility risk.
• Fertility preservation counseling is essential prior to HSCT, but options vary by disease type and patient age.
• In benign diseases without urgent HSCT, multiple fertility preservation methods (oocyte, ovarian tissue, sperm, testicular tissue freezing) are feasible.
• In malignant diseases, especially leukemia, time constraints limit fertility preservation, with sperm freezing possible in males but oocyte freezing often not feasible in females.
• Prepubertal patients have limited, mostly experimental fertility preservation options involving cryopreservation of gonadal tissue.

Clinical Implications

Clinicians should proactively counsel patients undergoing HSCT about the high risk of infertility and discuss fertility preservation options tailored to disease urgency, patient sex, and pubertal status. Early referral to reproductive specialists is recommended to optimize preservation strategies before gonadotoxic conditioning. Awareness of the limited fertility preservation options in malignant diseases and prepubertal patients is crucial for realistic patient counseling.

Conclusion

HSCT is associated with significant gonadal toxicity leading to infertility, necessitating early and individualized fertility preservation counseling. This systematic review provides critical data to inform clinical decision-making and improve patient quality of life post-transplant.

References

1. Snowden et al. -- Indications for HSCT
2. Saad et al. -- HSCT in Hematologic Diseases
3. FertiTOX Project -- Gonadotoxicity of Anticancer Therapies