Successful fertility preservation during curative therapy in female adolescent sickle cell anemia patients

Abstract Introduction: Sickle cell anemia (SCA) is a life limiting disease characterized by vasoocclusive episodes. Patients with SCD experience lifelong complications stemming from constant hemolysis and inflammation, leading to chronic end-organ damage. Disease modifying therapies that are routinely utilized may have a significant impact on reproductive health. In the past two decades, approximately 1200 patients have pursued curative therapy with either HSCT (hematopoietic stem cell transplant) or more recently GT (gene therapy). Fertility preservation (FP) options are now available to sickle cell patients who are exposed to potentially-gonadotoxic regimens prior to both HSCT and GT. FP in sickle cell patients, specifically ovarian stimulation as part of egg retrieval, can trigger vaso-occlusive crises (VOCs) and thromboembolic events reducing their ability to be carried out successfully. We report on two adolescents successfully supported through oocyte retrieval, avoiding these complications. Methods: Two adolescent females with homozygous SS disease (a 15 year old for GT, and a 16 year old for HSCT) followed a fertility preservation regimen for oocyte retrieval. This included a progestin suppression protocol and individualized gonadotropin dosing. The trigger medication was human gonadotropin dosing. Supportive care for SCD was managed by our hematology team in close collaboration with the reproductive endocrinology team managing the egg retrieval. Three interventions were employed by the hematology team to mitigate the risks of both their underlying sickle cell disease and their exposure to hormone therapy. The first was discontinuation of hydroxyurea for at least 90 days prior to oocyte collection. The second was transfusion therapy utilizing both erythrocytapheresis and partial manual exchange transfusions with weekly monitoring to maintain hemoglobin between 10-12 gm/dl and Hgb S<40% to reduce the risk of VOC during hormonal stimulation. The third intervention was prophylactic anticoagulation utilizing DOACs, or Direct Oral Anticoagulants at inception of FP until 36 hours prior to oocyte retrieval to decrease the risk of thromboembolic events. Results: Both patients were monitored with weekly CBC; transfusions were administered if their hemoglobin fell below 10g/dL, not to exceed 12g/dL. Prior to initiation of FP both patients underwent exchange transfusion to lower their hemoglobin S% to less than 30% which was then maintained between 21.6% and 31.4% for the 15 year old and between 7.3% and 31.7% for the 16 year old. There were no SCA complications such as VOC, and no thrombotic or bleeding complications Conclusion: Adolescent females who undergo FP with hormonal stimulation prior to HSCT or GT are at increased risk for serious complications including VOC, thrombosis and ovarian hyperstimulation. However, this procedure is preferable to other FP approaches such as ovarian tissue cryopreservation which requires surgical removal of one ovary. The three strategies we employed to support patients as they underwent FP prior to HSCT or GT were evidence-based and well-tolerated and were successful in avoiding these potential complications. Close communication and coordination between specialists was crucial for carrying out the three strategies.