Scoping review of current practices and recommendations on fertility preservation in sickle cell disease Free

Introduction: Sickle cell disease and its treatments, mainly hydroxyurea and transformative therapies, are associated with male and female infertility. Despite this, there is little data on fertility preservation in this population.

Objective:

This scoping review aims to examine the current practices and recommendations on fertility preservation access, insurance coverage, counseling, and referral to reproductive specialists for sickle cell disease.

Methods:

We reviewed articles between 2015 and 2025 that fulfilled our research objectives. Databases such as Web of Science and Science Direct were utilized to gather relevant articles. Our search included the terms “sickle cell fertility and gene therapy access or sickle cell fertility and transplant access,” “sickle cell fertility and gene therapy counseling or sickle cell fertility and transplant counseling”, “sickle cell fertility and gene therapy or sickle cell fertility and transplant”, and “insurance coverage for sickle cell fertility preservation”. We identified 890 articles written in English that referenced counseling for fertility, specialist referral indications, the rate of referrals prior to transformative therapy, and access to fertility preservation for patients with sickle cell disease. We excluded documents that focused on other hemoglobinopathies, oncology-related conditions, fertility after transformative interventions, or those that we were unable to access. All documents underwent a full text review, with 51 selected for qualitative analysis.

Results:

Articles were categorized into three major headings with occasional overlap noted, namely: referral, counseling, and access. Five articles discussed the importance of referrals, emphasizing that formal referrals or consultations should be made to a fertility service informing patients of their fertility preservation options prior to gene therapy or hematopoietic stem cell transplant. Pediatric and reproductive endocrinologists, gynecologists, and maternal fetal medicine experts were specially mentioned. Twenty-three articles reported on the significance of counseling, all of which stated that counseling should occur before any curative procedures.

Additionally, twenty-three articles examined sickle cell patients' access to fertility preservation, focusing on factors such as insurance coverage, affordability, access to stem cell donors, and available interventions. These patients were shown to face a significant financial burden as fertility preservation methods could cost thousands of dollars, excluding expenses for cryopreservation storage and appointments at specialized centers. Access to insurance coverage and subsidized costs through various programs were less likely to be available. Insurance coverage was largely dependent on the patient's location, with some European countries offering insurance that covered fertility preservation. In contrast, the USA coverage depended on the state. In lower-middle income countries, the availability of fertility preservation services for sickle cell patients was even less common. Disparities in fertility preservation were noted, particularly among black patients compared to their white, Hispanic, and Asian Pacific Islanders counterparts.

Conclusion

Fertility preservation in individuals with sickle cell primarily aims to enhance the chances of maintaining reproductive potential despite decreased fertility associated with the condition and curative treatments. One aspect that was not addressed is when counseling should begin, given that fertility preservation can start in pre-pubertal patients with sickle cell disease, facilitating earlier curative attempts. Additionally, these discussions can be initiated by the primary care provider or hematologist overseeing the patient's care and further elaborated upon by the fertility specialist to whom the patient is referred.

If counseling and referrals are effectively initiated, affordability remains the final barrier to fertility preservation services. This scoping review highlights the significant gaps in educating sickle cell patients about fertility preservation and the difficulties experienced with accessing treatments. It emphasizes the necessity for managing physicians and, by extension, the multidisciplinary team, to be well-equipped to educate and direct patients toward services that can enhance their reproductive potential. Furthermore, it advocates insurance coverage for this essential service.