Genetic Disorders and the Fetus. Группа авторов

McPhee SJ, Bottles K, Lo B, et al. To redeem them from death: reactions of family members to autopsy. Am J Med 1986; 80:665.

      1030 1030. Irvin NA, Kennell JH, Klaus MH. Caring for the parents of an infant with a congenital malformation. In: Warkany J, ed. Congenital malformations: notes and comments. Chicago: Year Book Medical Publishers, 1971.

      1031 1031. Klaus MH, Kennell JH. Caring for parents of an infant who dies: maternal–infant bonding. St Louis, MO: CV Mosby, 1976.

      1032 1032. Blood C, Cacciatore J. Parental grief and memento mori photography: narrative, meaning, culture and context. Death Stud 2014; 38:224.

      1033 1033. Flenady V, Boyle F, Koopmans L, et al. Meeting the needs of parents after a stillbirth or neonatal death. BJOG 2014; 121(Suppl 4):137.

      1034 1034. Furlong RM, Hobbins JC. Grief in the perinatal period. Obstet Gynecol 1983; 61:497.

      1035 1035. Shulman LP, Grevengood C, Phillips OP, et al. Family planning decisions after prenatal detection of fetal abnormalities. Am J Obstet Gynecol 1994; 171:1373.

      1036 1036. Rowe J, Clyman R, Green C, et al. Follow‐up of families who experience a perinatal death. Pediatrics 1978; 62:166.

      1037 1037. Forrest GC, Standish E, Baum JD. Support after perinatal death: a study of support and counseling after bereavement. BMJ 1982; 285:1475.

      1038 1038. Moldovan R, Pintea S, Austin J. The efficacy of genetic counseling for psychiatric disorders: a meta‐analysis. J Genet Couns 2017; 26:1341.

      1039 1039. Caldwell S, Wusik K, He H, et al. Development and Validation of the Genetic Counseling Self‐Efficacy Scale (GCSES). J Genet Couns 2018; 27:1248.

      1040 1040. Keller H, Wusik K, He H, et al. Further validation of the Genetic Counseling Self‐Efficacy Scale (GCSES): its relationship with personality characteristics. J Genet Couns 2020; 29(5):748.

      1041 1041. Borle K, Morris E, Inglis A, et al. Risk communication in genetic counseling: Exploring uptake and perception of recurrence numbers, and their impact on patient outcomes. Clin Genet 2018; 94:239.

      1042 1042. Clarke A, Parsons E, Williams A. Outcomes and process in genetic counseling. Clin Genet 1996; 50:462.

      1043 1043. Voorwinden JS, Plantinga M, Ausems M, et al. Cognitive and affective outcomes of genetic counseling in the Netherlands at group and individual level: a personalized approach seems necessary. Eur J Hum Genet 2020; 28:1187.

      1044 1044. Montgomery SV, Barsevick AM, Egleston BL, et al. Preparing individuals to communicate genetic test results to their relatives: report of a randomized control trial. Fam Cancer 2013; 12:537.

      1045 1045. Emery AEH, Raeburn JA, Skinner R. Prospective study of genetic counseling. BMJ 1979; 1:253.

      1046 1046. Sibinga MS, Friedman CG. Complexities of parental understanding for phenylketonuria. Pediatrics 1971; 48:216.

      1047 1047. Reynolds BD, Puck MH, Robinson A. Genetic counseling: an appraisal. Clin Genet 1974; 5:177.

      1048 1048. American College of Medical Genetics and Genomics. ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome‐scale sequencing. Genet Med 2015; 17:68.

      1049 1049. Sorenson JR, Swazey JP, Scotch NA. Effective genetic counseling: more informed clients. In: Reproductive pasts, reproductive futures: genetic counseling and its effectiveness. New York: Alan R. Liss, 1981:79.

      1050 1050. Swerts A. Impact of genetic counseling and prenatal diagnosis for Down syndrome and neural tube defects. Birth Defects Orig Artic Ser 1987; 23:61.

      1051 1051. Kessler S. Psychological aspects of genetic counseling. VI. A critical review of the literature dealing with education and reproduction. Am J Med Genet 1989; 34: 340.

      1052 1052. Davey A, Rostant K, Harrop K, et al. Evaluating genetic counseling: client expectations, psychological adjustment and satisfaction with service. J Genet Couns 2005; 14:197.

      1053 1053. Milunsky A. Your genetic destiny: know your genes, secure your health, save your life. Cambridge, UK: Perseus Books, 2001.

      1054 1054. Baars MJH, Scherpbier AJJA, Schuwirth LW, et al. Deficient knowledge of genetics relevant for daily practice among medical students nearing graduation. Genet Med 2005; 7:295.

      1055 1055. Marchant G, Barnes M, Evans JP, et al. From genetics to genomics: facing the liability implications in clinical care. J Law Med Ethics 2020; 48:11.

2 Preimplantation Genetic Testing

       Anver Kuliev and Svetlana Rechitsky

      Herbert Wertheim College of Medicine, Florida International University, Miami, FL and Reproductive Genetic Innovations, Northbrook, IL, USA

      Preimplantation genetic testing (PGT¹) is a practical option for couples at risk of having offspring with serious/fatal chromosomal or monogenic diseases. It has been used for up to 600 monogenic disorders (PGT‐M¹). Moreover, it has been used for human leukocyte antigen (HLA) typing (PGT‐HLA¹), enabling the births of many children whose matched bone marrows have proved life‐saving for siblings with congenital and acquired disorders requiring stem cell transplantation treatment.

      Analysis of single cells or a few cells with a limited amount of available DNA has always presented a technical challenge, especially when PGT is faced with the need for accurate and rapid results from whole‐genome amplification (WGA), followed by polymerase chain reaction (PCR) assays that are robust and sensitive. Next‐generation sequencing (NGS) has allowed for accurate identification and transfer of euploid embryos (PGT for aneuploidies (PGT‐A)¹).

      PGT‐M was initially applied for the same indications as prenatal diagnosis,^2–4 but was then expanded to conditions that had never been considered, such as late‐onset diseases with genetic predisposition and preimplantation HLA typing with or without testing for genetic disorders.^5–7

      PGT represents a natural evolution of the genetic disease prevention technology, from a period with limited genetic counseling and no prenatal diagnosis or treatment to a time when many options, including PGT, have become available.⁸ Furthermore, PGT has been applied in order to improve access to the new treatment methods for some severe conditions by stem cell transplantation, for which no traditional treatment approaches are available. The impact of PGT and stem cell treatment on existing policies for the prevention of genetic disease (see Chapter 36) is clear from the increasing use of PGT to avoid unnecessary termination of many wanted pregnancies and for preimplantation HLA typing.

Approaches to preimplantation genetic testing

      When prenatal genetic diagnosis was first considered in perspective, in 1984, the World Health Organization (WHO) emphasized the relevance of developing earlier approaches for genetic analysis with the possibility of diagnosis before implantation.^{9, 10} The following possibilities for PGT were mentioned: genetic analysis of the first or second polar bodies and embryo biopsy at the cleavage or blastocyst stage.^{10, 11} However, these approaches became possible only after introduction of the PCR assay¹² and success in micromanipulation and embryo biopsy.

First attempts at PGT were undertaken in mammalian embryos over 30 years ago,^13–18 when it was demonstrated that cells could be removed from mammalian preimplantation embryos and analyzed successfully without destroying the viability of the embryo in in vitro fertilization (IVF). PGT for human genetic disease was first demonstrated by Handyside et al.¹⁹ for X‐linked diseases and by Verlinsky et al.²⁰ for autosomal recessive disorders. Tens of thousands of children without detectable birth defects have been born following these procedures,^21–25 demonstrating that PGT