OBJECTIVE: Preimplantation Genetic Diagnosis (PGD) is, presently, a valid alternative to prenatal diagnosis for couples at high risk of pregnancies with genetic anomalies. PGD of single gene disorders, combined with Human Leukocyte Antigen (HLA) matching, represents one of the most recent applications in reproductive medicine. This strategy has emerged as a tool for couples at risk of transmitting a genetic disease to select unaffected embryos of a HLA tissue type compatible with that of an existing affected child. At delivering, stem cells from the newborn umbilical cord blood can be used to treat the affected sibling. Allogeneic haematopoietic stem cell (HSC) transplantation represents the only curative option for severe cases of haematopoietic disorders. The best possibilities of cure are provided by transplantation with HLA-identical donors. Unfortunately, this cannot be applied in the majority of cases because of the difficulty to find HLA-matched donors, even among family members. Umbilical cord blood from HLA-identical siblings has been reported as an excellent source of stem cells. Therefore, an increasing number of couples with a child affected by such a disease are requesting preimplantation HLA matching to conceive a healthy child who would became a future donor of HSC, to provide radical treatment for the existing affected recipient sibling. Here we present our experience on PGD of single gene disorders combined with HLA matching. MATERIALS AND METHODS: The PGD strategy involved a multiplex external/nested PCR allowing the simultaneous amplification of the causative mutations, STR markers linked to these regions for ADO detection, and a range of 10-15 informative HLA STR markers. Mutation analysis was carried out using the minisequencing technique. RESULTS: Preimplantation HLA matching was performed on 23 cycles (20 for -thalassemia, 1 for Wiscott-Aldrich syndrome and 2 for leukaemia) from 19 couples overall, involving the testing of 212 embryos in combination with a genetic disease, and of 4 embryos for HLA matching only. Five clinical pregnancies were obtained, 3 of them have been already born. Two pregnancies are still ongoing and were confirmed as healthy and HLA identical with the affected children by prenatal diagnosis. CONCLUSIONS: The current data confirm the feasibility of preimplantation HLA matching as a part of PGD, providing a realistic option for couples desiring an HLA-compatible child for the treatment of affected siblings.