Fertility Preservation for Women with Sickle Cell Disease (SCD)

Objective: Peripheral blood stem cell transplant (PBSCT) can now cure SCD in adults, but may result in a loss of future fertility. Little is documented regarding fertility preservation in women with SCD. The aim of this study was to perform fertility preservation for women with SCD scheduled for PBSCT.

Design: Prospective cohort of women with SCD undergoing fertility preservation prior to PBSCT at a large research hospital.

Materials and Methods: Patients underwent standard controlled ovarian hyperstimulation (COH) using an antagonist protocol cycle with leuprolide trigger under close multidisciplinary (including reproductive endocrinologists and hematologists) monitoring. All patients were continued on therapeutic or started on prophylactic anticoagulation prior to beginning COH, and maintained on hydroxyurea.

Results: Nine reproductive aged women were screened; 1 declined participation, 1 was diagnosed with unrecognized premature ovarian insufficiency, 1 had her fertility preservation cycle canceled due to poor response to fertility medications and 2 patients are scheduled for upcoming cycles. The remaining four women (ages 20, 34, 24, 27) successfully underwent COH, transvaginal oocyte retrieval and cryopreservation of mature eggs (n= 8, 13, 15, 21 oocytes, respectively). The third patient underwent two cycles due to low mature oocyte yield from her initial cycle. Headaches were reported by patients 1 and 2 following gonadotropin injections, with a negative neurologic workup including MRI in patient 2. Patient 3 underwent an exchange transfusion on day 10 of stimulation, which did not adversely impact serum reproductive hormone levels. Patients 3 and 4 reported an acute exacerbation of their chronic pain during COH, which responded well to intravenous fluids, IV and oral pain medications. Therefore, despite severe SCD and co-morbid conditions, the side effects were manageable. There were no venous thrombotic events.

Conclusion: These results provide support that fertility preservation can be safely performed in women with SCD under the care of a multidisciplinary team.  The safest stimulation protocol (i.e. antagonist cycle with leuprolide trigger for final oocyte maturation) was successful in all patients despite multiple risk factors for failed leuprolide trigger. Fertility preservation is important not only before PBSCT to cure their underlying disease, but also because of high rates of premature ovarian insufficiency in the SCD population post-transplant.

Support: Intramural NICHD and NHLBI, NIH.