Safety and Feasibility of Fertility Preservation and Fertility Outcomes in Patients with Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia Undergoing Gene Therapy.

Recently approved gene therapies for sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT) have expanded therapeutic options. However, myeloablative busulfan is associated with a significant risk of infertility. There are limited data on the safety, feasibility, and outcomes of fertility preservation in this population. We report the single-center experience of 40 patients who underwent gene therapy over the past 5 years. The cohort included 23 females (14 with SCD and 9 with TDT) and 17 males (8 with SCD and 9 with TDT). All female subjects underwent successful oocyte retrieval. Those with SCD had a median of 1.3 cycles (range, 1-2), whereas those with TDT had a median of 1.4 cycles (range, 1-3). Seven (50%) females with SCD had prior history of a thrombotic event, all of whom received anticoagulation prophylaxis, and none experienced thrombosis during ovarian stimulation. There were no SCD-related admissions from the procedure. Among males, the median number of cryopreserved sperm vials was lower in those with SCD (2 vials; range, 1-2) compared with those with TDT (6 vials; range, 1-15). Median sperm concentration was also lower in those with SCD (7.1 million/mL; range, 0-160) compared with TDT (80.4 million/mL; range, 0.9-421). Seventeen females had more than 1 year of follow-up, all of which had evidence of ovarian failure with undetectable anti-Müllerian hormone levels (<0.015 ng/mL). Two male subjects fathered children without the use of cryopreserved samples. Fertility preservation is safe, feasible, and should be considered for patients with SCD and TDT prior to gene therapies.