Allogeneic hematopoietic cell therapy (HCT) is an established cure for sickle cell disease (SCD); however, HCT conditioning regimens are known to be gonadotoxic. Anti-mullerian hormone (AMH) measures ovarian reserve, and follicle-stimulating hormone (FSH) defines premature ovarian insufficiency (POI) at values >40 mIU/mL in pubertal females. The present study was conducted to assess ovarian reserve and function before and after transplantation in pediatric and adolescent females with SCD treated with allogeneic HCT between January 2015 and June 2020 at Children's Healthcare of Atlanta. In this retrospective review of 17 females age <21 years with SCD who had AMH levels measured at baseline and at 2 years post-HCT, AMH levels were categorized as normal, low, or undetectable, and FSH levels were measured and used to identify pubertal females who had developed POI. Demographic and treatment data were abstracted from the institutional database and medical records, and a descriptive statistical analysis was conducted. Of the 17 patients in the study cohort, 14 had been treated with hydroxyurea and 3 had chronic transfusions but with no significant iron overload. AMH levels were normal in 15 patients (88%) and low in 2 patients (12%) at baseline. The median age at HCT was 7.5 years (range, 3.7 to 20.3 years), and 14 patients (82%) underwent matched related donor HCT. After HCT, 15 patients (88%) had undetectable AMH and 2 (12%) had low AMH, with no apparent differences by HCT conditioning regimen. No pubertal patients had POI at baseline, whereas 55% of pubertal patients had progressed to POI by 2 years post-HCT. In this cohort, the majority of females had normal AMH levels at baseline but undetectable levels after HCT. Females with SCD considering HCT should be counseled about the treatment-related risk of gonadal dysfunction. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Conditioning regimens for hematopoietic cell transplant (HCT) in patients with sickle cell disease (SCD) place patients at risk for reproductive health issues. The purpose of this study was to assess reproductive health and reports of fertility counseling in patients with SCD who received a transplant. This was a secondary analysis of gonadal hormone production, future infertility risk assessment, and parent-proxy/patient reports of fertility counseling in SCD transplant recipients who are currently pubertal and were enrolled in the Atlanta sites of the Sickle Cell Transplant Evaluation of Long-term and Late Effects Registry (STELLAR) between May 2017 and October 2023. Clinical information was abstracted from medical records and reproductive health survey data from the STELLAR database. Descriptive statistics were reported as median (interquartile range [IQR]) or percentages. There were 20 females and 12 males in the study population. Females were median (IQR) 19.6 (9.4) years old and males 20.8 (11.4) years old at the time of the study. Transplants most commonly occurred in the decade 2010 to 2019 at 10.7 (4.8) years old for females and 11.1 (4.1) years old for males. Most participants received bone marrow stem cells (95.0% females, 100.0% males) from matched sibling donors (90.0% females, 100.0% males). Participants received one of seven HCT conditioning regimens with cyclophosphamide equivalent doses ranging from 3388 to 9706 mg/m². The majority of females (90.0%) had diminished ovarian reserve with low anti-Mullerian hormone levels, and 61.1% had premature ovarian insufficiency with two follicle-stimulating hormone levels (FSH) ≥40 mIU/mL post-HCT. All males had normal testosterone levels, but 63.6% had elevated FSH levels suggestive of impaired spermatogenesis post-HCT. Parent proxies (for patients <18 years old) and patients ≥18 years old completed surveys 9.0 years (5.2) and 7.9 years (9.3) since HCT in females and males respectively. Twenty-five percent of parent proxies and 45% of patients reported that they had not been informed by a healthcare provider of the risk of infertility post-transplant. There are high rates of gonadal dysfunction post-HCT, but many parent proxies and patients do not recall being told of the risk for future infertility. More effective methods of education are warranted to ensure SCD patients and their families clearly understand the risk for reproductive health issues post-HCT.