Title page -- Contents -- Participants -- Declarations of personal interest -- Preface -- 1 Genetic aetiology of infertility -- Introduction -- Female infertility -- Evidence of a genetic contribution -- Genetic causes -- Male infertility -- Chromosome disorders -- Three Y chromosome microdeletions -- Autosomal genes -- Genetics and epigenetics -- Conclusion -- References -- 2 Disorders of sex development -- Introduction -- Human sex development -- Chromosomal sex -- Gonadal and phenotypic sex -- Other sexually dimorphic processes: germ cell fate and gonad position -- Early postnatal changes -- Disorders of sex development -- Nomenclature -- Classification and diagnosis -- Sex chromosome DSD -- 46,XY DSD -- Gonadal (testicular) dysgenesis -- 46,XX DSD -- Ovarian development defects -- Androgen excess -- New challenges and opportunities in reproductive genetics and DSD -- Prenatal karyotyping/genotyping and CAH treatment -- Karyotype/phenotype discordance and prenatal counselling -- Early postnatal management -- The multidisciplinary team -- Molecular diagnosis and high-throughput analysis -- Long-term outcome -- Fertility -- Acknowledgements -- References -- 3 Preimplantation genetic diagnosis: current practice and future possibilities -- History of preimplantation genetic diagnosis -- PGD as a clinical service -- Why do people request PGD? -- The process of PGD -- Preparation for PGD -- Ovarian stimulation -- Method of oocyte fertilisation -- Embryo biopsy -- Embryo transfer -- Number of embryos for transfer and cryopreservation -- Success of PGD and paediatric outcomes -- Number of cycles and pregnancy rates -- Paediatric outcome -- Regulation of PGD -- Conditions for which PGD is available -- Funding -- PGD for single-gene disorders and chromosomal rearrangements -- Single-gene disorders -- Chromosome rearrangements and sex selection.

Chromosome rearrangements -- Sex selection -- Preimplantation genetic screening -- Difficult issues -- PGD for HLA matching -- Late-onset disorders -- Non fully penetrant disorders -- Selection for disability -- The future of PGD -- Acknowledgements -- References -- 4 Ethical aspects of saviour siblings :procreative reasons and the treatment of children -- Two distinctions -- Reasons and actual treatment -- Third-party intervention -- Reasons and saviour siblings -- How do we deal with bad reasons? -- Two further thoughts -- Conclusions: judging reasons -- The treatment of saviour siblings -- Parental freedom -- Live organ donation by children -- Conclusion -- References -- 5 Epigenetics, assisted reproductive technologies and growth restriction -- Epigenetics: overview -- Genomic imprinting -- DNA methylation controls genomic imprinting -- Assisted reproductive technologies -- Embryo culture -- Superovulation -- ART children's growth and development -- Genomic imprinting and growth -- Genomic imprinting and the placenta -- ART and genomic imprinting syndromes -- The significance of postnatal genomic imprinting -- Summary -- References -- 6 Fetal stem cell therapy -- Introduction -- Sources of stem cells -- Haematopoietic stem cells -- Fetal mesenchymal stem cells -- Bone marrow, liver and blood -- Placenta and membranes -- Amniotic fluid -- Umbilical cord -- Development of in utero transplantation -- Rationale -- Preclinical development in wild types -- Preclinical development in disease models -- Muscular dystrophy -- Osteogenesis imperfecta -- Clinical development of in utero transplantation -- In utero transplantation with haematopoietic stem cells -- Mesenchymal stem cells for osteogenesis imperfecta -- Paediatric experience -- Fetal experience -- Route to clinical translation -- Barriers to engraftment.

Production of clinical-grade mesenchymal stem cells -- Rescue treatment -- Conclusion -- References -- 7 Prenatal gene therapy -- Summary -- Introduction -- The advantage -- Candidate diseases -- Vectors for prenatal gene therapy -- The evidence: preclinical proof-of-principle studies -- Issues facing prenatal gene therapy -- Targeting therapy to the correct organ -- Manipulating the vector -- Methods and timing of delivery to the fetus -- Effect of fetal exposure on vectors -- Germline transmission -- Choice of disease -- Length of expression -- Growth of the vector recipient -- Vector silencing -- Integrating vectors and insertional mutagenesis -- Pre-existing maternal immunity -- Regulating transgene expression -- Fetal and maternal immune response to vector and transgene -- Reversion to wild type vector -- Safety of fetus, mother and her future progeny -- Ethical concerns -- Application in humans -- Fetal somatic gene therapy in practice -- The future of prenatal gene therapy -- References -- 8 Ethical aspects of stem cell therapy and gene therapy -- Introduction -- Implication in evil -- Reproductive effects -- Blurring of the line between research and treatment -- Blurring of the line between treatment and enhancement -- Consent for fetuses and children -- Cost-effectiveness and resource allocation -- Conclusion -- Acknowledgements -- References -- 9 Fetal dysmorphology: the role of the geneticist in the fetal medicine unit in targeting diagnostic tests -- Introduction -- Increased nuchal translucency with a normal karyotype -- Identification of fetal abnormalities at the 11-13 week scan -- Holoprosencephaly -- Omphalocele -- Anomalies detected at the 18-20 week scan -- Skeletal dysplasias -- Cardiac abnormalities -- Cleft lip and palate -- Arthrogryposis -- Hydrops -- Sex reversal -- Isolated limb abnormalities -- Gastrointestinal disorders.

Renal disorders -- Summary -- References -- 10 Fetal karyotyping: what should we be offering and how? -- Background -- Current PND service delivery models in the UK -- New technologies and PND -- aCGH and PND -- Potential PND service reconfiguration driven by aCGH -- Acknowledgements -- References -- 11 Non-invasive prenatal diagnosis: the future of ptrenatal genetic diagnosis? -- Introduction -- Current clinical applications -- Fetal sex determination -- Single-gene disorders -- Future possibilities -- Diagnosis of aneuploidy -- Other laboratory issues -- Ethics, education and counselling -- The way forward -- Acknowledgements -- References -- 12 Non-invasive prenatal diagnosis for fetal blood group status -- Introduction -- Molecular basis for D polymorphism -- Fetal D testing in alloimmunised (high-risk) pregnant women -- The problem of including internal controls -- Fetal testing to ascertain the requirement for antenatal anti-D immunoglobulin prophylaxis -- Fetal genotyping for other blood groups -- Quality assurance -- Conclusion -- References -- 13 Selective termination of pregnancy and preimplantation genetic diagnosis: some ethical issues in the interpretation of the legal criteria -- Introduction -- The severity of a condition: whose interests? -- Interpreting the law on selective termination of pregnancy and PGD -- Termination of pregnancy -- PGD -- Conclusion -- References -- 14 Implementation and auditing of new genetics and tests: translating genetic tests into practice in the NHS -- Background -- The UK approach to genetic test evaluation -- International frameworks -- The ACCE framework translated to a gene dossier -- Test definition -- Analytical validity -- Clinical validity -- Clinical utility -- Ethical legal and social issues -- Gatekeeping -- Information for commissioning -- Auditing effectiveness.

Are the UKGTN systems future-proof? -- What changes or new systems should be considered? -- References -- 15 New advances in prenatal genetic testing: the parent perspective -- Introduction -- ARC's contact with parents making decisions about invasive diagnostic tests -- Implications for parents of the future implementation of NIPD -- NIPD and the challenge of informed consent -- Lessons to be learned from antenatal ultrasound scanning -- New techniques in preimplantation genetic screening and diagnosis -- Ethical concerns: 'eugenics' and 'designer babies' -- Private services -- Conclusion -- References -- 16 Informed consent: what should we be doing? -- Introduction: consent, choices and decisions -- Practicalities: facilitating informed decisions -- Information -- Decision making -- Evaluating the performance of prenatal screening and testing programmes -- Knowledge -- Values and attitudes -- Behaviour and the predictive power of attitudes -- Including a measure of decision making -- Evaluating screening programmes: what else can we do? -- References -- 17 Consensus views arising from the 57th Study Group: Reproductive Genetics -- Clinical practice -- Health policy -- Saviour siblings -- Fetal gene and stem cell therapy -- Research -- Breakthrough technologies -- Embryonic stem cell-derived germ cells -- Fetal stem cell and gene therapy -- Epigenetic regulation -- Development of existing technology -- Other recommendations -- Index.