Fertility Recovery Following Allogeneic Bone Marrow Transplantation in Aplastic Anemia; A Study of 157 Patients
Authors: Alfraih Feras , Ahmed Shad , Kim Dennis Dong Hwan , Rasheed Walid , Aldawsari Ghuzayel , Alsharif Fahad , Mohamed Said Y , Hanbali Amr , Ahmed Syed Osman , Shaheen Marwan , Chaudhri Naeem A. , Al Mohareb Fahad , Al-Jurf Mahmoud , Alzahrani Hazza A 
Published: October 2019

Abstract
Introduction :
Infertility is a major late effect of hematopoietic stem cell transplants (HSCT). In aplastic anemia (AA) patients, although the fertility recovery rate is relatively higher than other diseases but the exact incidence and risk factors are not very well studied. In this study, we attempted to evaluate incidence and the impact of patientÕs characteristics and transplantation procedures on fertility recovery following allogeneic HSCT for adolescent and adults patients with AA.
Methods :
A total of 157 patients who were at least 14 years old with AA receiving HSCT between year 1987 and 2014 at our center were reviewed. Patients who survived at least 2 years following HSCT and either married or in relationship were included in the analysis and evaluated for fertility following HSCT. 87 patients were eligible for the study. Questionnaire survey and long-term charts were used for data collection. With a response rate and or available information of 63% patients, 55 patients were identified and stratified into fertility recovery (FR+) versus non-fertility recovery (FR-) group. Fertility recovery was defined by a pregnancy of the patient or his partner.
Results:
Median age for all patients is 23 years (range, 14 -50), 44% (n=24) between 14-20 years old, 51% (n=28) between age 20-40 years and 5% (n=3) > 40 years. 51% (n=28) were females. Matched related donor was used for majority of patients 96% (n=53). GVHD prophylaxis was CSA/MTX for 93% (n=51,). Conditioning regimen was Cyclophosphamide/Flu in 25 (45%), Cyclophosphamide /ATG in 18 patients (35%) and others in 12 patients (20%). Bone marrow was the source of stem cells for 52 patients (94%).
A median follow-up of 8 years for survivors (range, 0.3 -23) showed 45 patients (82%) had FR+ while 10 patients (18%) were FR-. Median duration of fertility recovery (from delivery to BMT) was 6 years (range, 0.8-19) with significant difference based on age groups, 4 years for patients 20-40 years (n=29, 53%) versus 8 years for those < 20 years (n=24, 44%), (p=0.002), (Figure 1). None of the patients >40 years old (n=2, 4%) had fertility recovery.
Comparison based on gender showed no significant difference. Males had a median duration of fertility recovery of 5.9 years, (range 0.6-14.9) versus 6.2 years, (range, 0.8-15.2) (p=0.31) females. The overall median number of pregnancies was 2 (range, 1-6). For males, it was 2 (range, 1-6) while 1.5 (range, 1-5) for females (p=0.26). Deliveries occurred in natural ways in (95%) while C-section for (5%). All deliveries were without fetal abnormalities.
Univariate analysis of risk factors for fertility recovery showed age group (p=0.03) and chronic GVHD (p=0.05) are important factors. Neither gender of patients or type of preparative regimens used for HSCT (Cyclo/ATG vs Cyclo/Flu) was a risk factor. In multivariate analysis, age group was the only confirmed an independent risk factor for fertility recovery (p=0.02) [HR= 2.02, CI=1.012-3.64).
Conclusion:
The present study suggested that the incidence of fertility recovery following HSCT for patients with aplastic anemia is high with no significant differences between males and females. Patients between the ages of 20-40 years at the time of HSCT have significantly shorter recovery period. Age was the only independent risk factor for fertility recovery while there was no impact of whether ATG or Fludarabine was used in addition to Cyclophosphamide as preparative regimen.
Figure 1. Figure 1.

Disclosures
Kim: Bristol-Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding.