Pregnancy Outcome Following Haematopoietic Stem Cell Transplantation.
Authors: Kulkarni Samar , Ethell Mark , Treleaven Jennifer , Saso Radovan , Brennan Joy , Kaczmarek Pawel , Alvares Caroline , Horton Clive , Saran Frank , Kanagasabapathy Pamala , Hiwarkar Prashant , Appiah-Cubi Stella , Dungarwala Moez , Powles Raymond , Morgan Gareth , Potter Michael 
Published: October 2019

Abstract
Between March 1973 and August 2003, 747 patients (M: 430, F:317; median age: 29yr, range:1–65) who survived for at least 1 yr. post stem cell transplant and were 15 to 65 years of age (median: 38, range:15–71) at the time of last follow-up (LFU) were analysed to study the incidence and outcome of pregnancies. At the time of transplantation, 138 patients were pre-pubertal (M: 79, F: 59, p=0.8). Transplants were allogeneic (n=429, median age: 28yr), autologous (n=304, median age: 32) or syngeneic (n=14, median age: 37) and were performed for Ac. Leukaemia (n=583), Chr. Leukaemia (n=82) or other diseases (n=82). Patients with Myeloma who received Autograft were not included. Conditioning included TBI in 561 patients using either single fraction (n=478) or a fractionated schedule (n=83) and 168 patients also received cranial radiation. Stem cell source was marrow (n=573), PBSC (n=166) or both (n=8). GVHD prophylaxis was CyA alone (n=188), CyA with another agent (n=227) or other measures (n=14). 79 patients received more than one transplant. The probability of overall survival in this group of patients was 65% at 10yr. Median follow-up was 7 yr. (range: 1–33). Twenty seven patients (10 females and 17 partners of male patients) had 41 pregnancies and sired 45 children, including 4 twin pregnancies. The probability of conception was 4% at 10yr. Pregnancies occurred in 17/429 allografts (3.96%; 6/186 females; 11/243 males), 8/304 autograft patients (2.63%; 4/123 females, 4/181 males) and 2/14 syngeneic transplants (14.3%; 0/8 females, 2/6 males). Amongst 10 female patients 3 had assisted conception and 7 had natural pregnancy. Amongst 17 partners of male patients, 5 had assisted conception, 11 had natural conception and 1 had assisted conception followed by natural pregnancy. In uni-variate analysis chances of becoming pregnant were higher with age> 15yr. at transplant (5% vs. 1% at 10 yr., p<0.001), non-TBI conditioning (9% vs. 2%, p=0.001), age between 20–45 at LFU (5% vs. 2%, p=0.005) and use of PBSC for transplant (8% vs. 5%, p<0.001). The highly significant correlation between use of PBSC and use of non-TBI conditioning probably explains why PBSC had a significant association with pregnancy on univariate analysis. On multi-variate analysis non-TBI conditioning (RR: 3.7, 95% CI: 1.7–8.3, p=0.0014), age at transplant>15 yr. (RR: 11.6, 95% CI: 1.6–86.3, p=0.02) and age of 20–45 at LFU (RR: 5.53, 95% CI: 1.9–16.1, p=0.002) were independently associated with higher chances of conception. Two pregnancies resulted in miscarriages leading to 3 foetal deaths (2/42, 5%; 3/45, 7%). Four babies were born prematurely and required admission to neonatal unit and 2 died after 6 weeks. None had congenital malformations. Currently, 40 children are alive and well; 26 after natural conception and 14 after assisted fertilization. In conclusion, even though the chances of conception are lower in patients undergoing transplant, especially after TBI conditioning, pregnancy outcomes following natural and assisted conception are likely to be similar in terms of chances of successful outcome.