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45 A. Kuliev, Practical Preimplantation Genetic Diagnosis,DOI 10.1007/978-1-4471-4090-0_3, © Springer-Verlag London 2012 3 Single-gene disorders are the fi rst group of indications for which preimplantation genetic diagnosis (PGD) was originally introduced 21 years ago, with the purpose of performing genetic testing before pregnancy, in order to establish only unaffected pregnancies and avoid the need for pregnancy termination, which is the major limitation of traditional prenatal diagnosis [ 1, 2 ] . Despite the requirement for ovarian hyper-stimulation and in vitro fertilization (IVF), needed to perform genetic testing of oocyte or embryo prior to transfer, PGD has been accepted in most parts of the world [ 3, 4 ] . At least 10,000 PGD cycles were performed for single-gene dis-orders and, as will be shown below, is presently offered for some indications that have never been practiced in prenatal diagnosis, such as late-onset diseases with genetic predisposition, and preim-plantation HLA typing, making PGD not only an alternative but also a complement to prenatal diagnosis [ 5– 8 ] . The progress of PGD has been extensively reviewed, so the present book will mainly concentrate on those aspects of PGD that are useful for reproductive medicine and genetics practices, including available PGD approaches for different groups of genetic disorders, their accuracy, and major indications compared to pre-natal diagnosis, and present practical details use-ful for the realization of PGD for each of the conditions described. Indications for PGD were initially similar to those practiced in prenatal diagnosis and applied for those at-risk couples that could not accept pregnancy termination, expected in 25–50% of cases following prenatal diagnosis, depending on the mode of inheritance. However, these indica-tions have been extended beyond those for prena-tal diagnosis, and currently include the conditions with a low penetrance, late-onset disorders with genetic predisposition, and HLA typing with or without testing for causative genes [ 8 ] . The list of disorders, for which PGD has been applied, according to our experience, now comprises close to 300 conditions (Table 3.1 ), with most frequent ones still being cystic fi brosis (CFTR), hemoglo-bin disorders, and some of the dynamic muta-tions, such as myotonic dystrophy. Initially, the choice between prenatal diagnosis and PGD mainly depended on the patient’s attitude to termination of pregnancy, which is strongly in fl uenced by social and religious factors, but steadily it is becoming a part of family planning for couples at risk to ensure having only unaf-fected pregnancy, especially when there is a risk of having offspring with severe late-onset com-mon disorders with a strong genetic predisposi-tion [ 8 ] . However, the majority of patients are still unaware of the availability of PGD, due to a rela-tive novelty of the procedure. So there is an obvi-ous need for increasing awareness of PGD both for couples at risk and the medical profession, who require information about bene fi ts, accuracy, safety, and expected risks of the procedure. Tables 3.2 and 3.3 present our overall data of 2,158 PGD cycles for single-gene disorders, which is the world’s largest experience in one cen-ter. A total of 938 of these cycles were performed by PB approach, involving the retrieval and testing Preimplation Diagnosis for Single-Gene Disorders