Abstract 9
Introduction
Thalassemia is the most common monogenic disease worldwide and is rampant in Southeast Asia, including Thailand. Affected patients require lifelong palliation and are curable only by hematopoietic stem cell transplantation (HSCT). Preimplantation with genetic diagnosis (PGD) with human leukocyte antigen (HLA) match (PGD‐HLA) can establish a pregnancy with an unaffected and HLA‐compatible embryo, the HSCs of which, when successfully born, can be used in a curative HSCT of an affected sibling.
Objective
The aim of this study was to investigate the outcomes of patients seeking assisted conception and PGD‐HLA for thalassemia exclusion and treatment of an affected sibling in a single Thai center.
Methods
A retrospective analysis of outcomes of blastocyst PGD for α‐ and β‐thalassemia, with HLA matching, from 2007 to 2016 at Superior A.R.T. (Bangkok, Thailand). Main outcomes included the proportion of biopsied cycles with at least one screened embryo suitable for transfer, implantation rate, live birth rate, and curative HSCT post PGD‐HLA.
Results
In 221 cycles from 138 patients (50 patients/104 cycles requiring HLA matching), 90.5% had embryo(s) biopsied for genetic testing, with 94.3% of thalassemia and 63.2% of thalassemia‐HLA cycles having clinically suitable embryo(s). Overall 1,180 blastocysts were screened, with 58.6% of thalassemia‐PGD and 16.8% of thalassemia‐PGD‐HLA embryos suitable for transfer. There were 119 (76/43) embryo transfers for thalassemia and thalassemia‐HLA cases, resulting in overall clinical pregnancy rates of 54.6%, implantation rates of 45.7%, and live birth rates of 44.1%. Of fifteen thalassemia‐PGD‐HLA births, ten have provided HSC for curative bone marrow (BM)‐HSCT of ten thalassemia‐affected siblings (using umbilical cord blood‐UCB in eight, UCB and BM in one, and BM in one). Another three affected children await HSCT, one succumbed to thalassemia before an HSCT, and one was lost to follow up (Table 1).
Table 1.
Details of PGD‐HLA HSCT
| Patient number | Recipient sex | PGD‐HLA donor | Patient origin | Affected sibling thalassemia | HSC source | Recipient age at HSCT, months | HSCT status | HSCT‐related complications |
|---|---|---|---|---|---|---|---|---|
| Sex and (Dx) | Mutation Dx | Country HSCT performed | ||||||
| 1 | M | M (Normal) | Thailand | BThal/HbE Cd.17 (A>T)/HbE |
UCB | 59 | Success Thailand |
None |
| 2 | F | F (HbE trait) |
Thailand | BThal/HbE HbE / IVSII‐654 (C>T) |
UCB | 45 | Success Thailand |
None |
| 3 | F | M (HbE trait) |
Thailand | BThal/HbE Cd.41/42 (‐TCTT)/HbE |
UCB | 67 | Success Thailand |
None |
| 4 | M | F (HbE trait) |
Thailand | BThal/HbE Cd.41/42 (‐TCTT)/HbE |
UCB | 39 | Success Thailand |
None |
| 5 | M | F (Normal)/ F (IVSI‐5) |
Thailand | BThal/HbE HbE / IVSI‐5 (G>C) |
UCB Twins | 56 | Success Thailand |
Mild veno‐occlusive disease, completely resolved |
| 6 | F | F (Normal) |
Thailand | homoB‐thal IVSII‐654 (C>T) / Cd.41/42 (‐TCTT) |
UCB | 45 | Success Thailand |
None |
| 7 | M | M (Beta‐28) |
Thailand | homoB‐thal beta‐28 (A>G) / Cd.17 (A>T) |
UCB in/ex‐utero collection | 36 | Success Thailand |
None |
| 8 | F | F (HbE trait) |
Thailand | B‐thal/HbE HbE / IVSII‐654 (C>T) |
UCB + BM same donor; | Awaiting BM‐HSCT due to high recipient weight | ||
| 9 | F | M (Normal) |
Cambodia | B‐thal/HbE HbE / Cd.17 (A>T) |
BM (BM donor age 12 months) (UCB not used) | 132 | Success India |
None |
| 10 | M | F (Normal) |
Cambodia | B‐thal/HbE HbE / IVSII‐654 (C>T) |
UCB + BMc |
Awaiting HSCT | ||
| 11 | F | M (Normal) |
China | homoB‐thal beta‐28/ Cd.41/42 (‐TCTT) |
UCB + BM same donor; (BM donor age 36 months) | 108 | Success China |
None |
| 12 | F | M (Normal) |
India | homoB‐thal IVSI‐5 (G>C) / IVSI‐1 (G>A) |
UCB | 60 | Success India |
None |
| 13 | M | M (Carrier) |
India | homoB‐thal IVSI‐5 (G>C) / IVSI‐5 (G>C) |
N/A | Unknown | ||
| 14 | F | M (IVSI‐5) |
India | homoB‐thal Cd.41/42 (TCTT) / IVSI‐5 (G>C) |
N/A | No HSCT, recipient deceased | ||
| 15 | F | F (αα/‐‐SEA) |
Vietnam | HbH‐CS disease (‐‐/αCsα) |
UCB | Awaiting HSCT | ||
Abbreviations: BM, bone marrow; Dx, diagnosis; F/M, female/male; HLA, human leukocyte antigen; HSC, hematopoietic stem cell; HSCT, hematopoietic stem cell transplantation; N/A, not applicable; PGD, Preimplantation genetic Diagnosis; UCB, umbilical cord blood.
Discussion
Our favorable thalassemia PGD and PGD‐HLA outcomes are in agreement with those reported from European Society of Human Reproduction and Embryology (ESHRE) centers, pointing out that Asia has come of age in providing PGD and PGD‐HLA diagnostic and clinical services for the prevention and treatment of thalassemia. The ultimate success in PGD‐HLA is the cure of a thalassemia‐affected sibling by HSCT. Our PGD‐HLA HSCT series, the first and largest performed entirely in Asia, presents ten successful and three pending cures.