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Hemoglobinopathies are the most frequent indications for preimplantation genetic diagnosis (PGD), allowing couples at-risk of bearing offspring with thalassemia and sickle cell disease to reproduce without fear of having an affected child. The present experience includes PGD for sickle cell disease, α- and β-thalassemia (α- and β-thal). We present here the results of the world's largest experience of over 395 PGD cycles for hemoglobin (Hb) disorders, resulting in the birth of 98 healthy, hemoglobinopathy-free children, with seven pregnancies still ongoing. One-third of these cases were performed in combination with HLA typing, allowing the birth of unaffected children who were also HLA identical to the affected siblings with hemoglobinopathies in these families, with successful or pending stem cell transplantation in a dozen of them. The results show that PGD is presently a practical approach for prevention of hemoglobinopathies, gradually also becoming a useful approach to improving access to HLA-compatible stem cell transplantation for this group of diseases.

Standard preimplantation genetic diagnosis (PGD) cannot be applied for de-novo mutations (DNM), because neither origin nor relevant haplotypes are available for testing in single cells. PGD strategies were developed for 80 families with 38 genetic disorders, determined by 33 dominant, three recessive and two X-linked DNM. All three recessive mutations were of paternal origin, while of 93 dominant mutations, 40 were paternal, 46 maternal and seven detected in affected children. The development of specific PGD strategy for each couple involved DNA analysis of the parents and affected children prior to PGD, including a mutation verification, polymorphic marker evaluation, whole and single sperm testing to establish the normal and mutant haplotypes and PGD by polar body analysis and/or embryo biopsy. Overall, 151 PGD cycles were performed for 80 families, for which a specific PGD design has been established. The application of these protocols resulted in pre-selection and transfer of 219 (1.72 per cycle) DNM-free embryos in 127 (84.1%) PGD cycles, yielding 63 (49.6%) unaffected pregnancies and birth of 59 (46.5%) healthy children, confirmed to be free of DNM. The data show feasibility of PGD for DNM, which may routinely be performed with accuracy of over 99%, using the established PGD strategy.

Preimplantation genetic testing (PGT) is currently extended to an increasing number of late-onset common disorders with genetic predisposition, including inhered forms of breast and ovarian cancer (HBOC), determined by BRCA1/2 genes. Prevention and treatment of HBOC presents a real challenge, because of incomplete penetrance and variable expressivity of predisposing BRCA1/2 genes. The major problem is that preventive management may not affect penetrance of these genes, which may lead to HBOC even after prophylactic bilateral mastectomy or oophorectomy. So PGT for BRCA1/2 genes is an extremely attractive approach, as it allows not only avoiding the transfer of mutant embryos, but also provides the possibility of having children free from predisposition to HBOC. The present paper summarizes the first systematic experience of 149 PGT cycles for BRCA1/2 gene mutations, which resulted in birth of 68 healthy, disease predisposition free children, demonstrating important clinical implications of PGT as practical means for couples carrying BRCA1/2 predisposing genes.

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