Pregnancy and pregnancy outcomes after hematopoietic stem cell transplantation in childhood: a cross-sectional survey of the EBMT Pediatric Diseases Working Party

STUDY QUESTION: What are the characteristics of patients with conceptions transplanted in childhood and adolescence? SUMMARY ANSWER: Insemination and conception after hematopoietic stem cell transplantation (HCT) in childhood or adolescence was possible, even after myeloablative conditioning regimes, although some patients required reproductive medicine support. WHAT IS KNOWN ALREADY: Preparative regimens of HCT are highly gonadotoxic, which leads to gonadal failure and pubertal development disorders. There are few population-based studies assessing the risk of future infertility in children after HCT. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective study to investigate natural or assisted conceptions and their outcomes in patients <18 years old before their first transplantation who received HCT between 1995 and 2016 and were in the European Society for Blood and Marrow Transplantation (EBMT) registry. Adoptions were excluded from the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Detailed information concerning pregnancy occurrences and outcomes were obtained by a separate questionnaire. Quantitative variables were presented as medians with their interquartile range (IQR) or range, and categorical variables were presented as frequencies and percentages. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 62 988 pediatric patients received a first HCT in EBMT centers between 1995 and 2016. Pregnancy was reported in 406 patients in the database. The median age at transplantation was 15.7 (range: 0.7-18) years, and the median age at declared conception was 25.0 (range: 16.3-38.8) years. Details concerning the first pregnancy and pregnancy outcome were obtained from 99 patients (24%) from the returned questionnaires. The median age at delivery or pregnancy interruption of the females was 23.0 (IQR: 20.8-27) years, with a median time after transplant of 10.7 (IQR: 6.6-15.4) years. Compared with the mean age of healthy women at their first child's birth (29 years old), the transplanted women delivered 5 years earlier (mean: 24.3 years). In terms of conception modality, 13/25 (52%) females conditioned with total body irradiation (TBI) and 50/52 (96%) of those conditioned without TBI conceived naturally. All seven male patients who had been conditioned with TBI achieved fatherhood but required assisted fertilization or used their cryopreserved sperm. In the females, 63/70 (90%) of all conceptions resulted in a live birth, 49/63 (84.5%) were at term and 43/46 (93%) had normal birthweight. Cesarean delivery was performed in 9/61 (15%) especially in women who had received a myeloablative regimen. LIMITATIONS, REASONS FOR CAUTION: In the EBMT pediatric dataset, the age at last follow-up or death was <17 years for 75% of the patients, therefore a longer follow-up for all patients would be necessary to calculate the cumulative incidence of conception for patients transplanted during childhood and allow all patients to realize their reproductive willingness/potential. WIDER IMPLICATIONS OF THE FINDINGS: Reproductive health surveillance and fertility preservation counseling are important in younger transplanted patients. Our results showed that there is a window of opportunity to conceive naturally or with reproductive medicine support.

Automated summary

The study found that insemination and conception after hematopoietic stem cell transplantation (HCT) in childhood or adolescence are possible, with some patients possibly requiring reproductive medicine support. Traditional HCT preparative regimens can lead to gonadal failure and pubertal development disorders. Reproductive health surveillance and fertility preservation counseling are crucial for these patients.