Preimplantation genetic diagnosis (PGD) has recently been offered for couples with an inherited predisposition for late onset disorders. This paper presents the results of PGD for a group of couples at risk for producing children with cancer predisposition. Using a standard IVF procedure, oocytes or embryos were tested for different mutations predisposing to cancer, preselecting and transferring only mutation-free embryos back to the patients. The procedure was performed for patients with predisposition to familial adenomatous polyposis coli (FAP), Von Hippel-Lindau syndrome (VHL), retinoblastoma, Li-Fraumeni syndrome, determined by p53 tumour suppressor gene mutations, neurofibromatosis types I and II and familial posterior fossa brain tumour (hSNF5). Overall, 20 PGD cycles were performed for 10 couples, resulting in preselection and transfer of 40 mutation-free embryos, which resulted in five unaffected clinical pregnancies and four healthy children born by the present time. Despite the controversy of PGD use for late onset disorders, the data demonstrate the usefulness of this approach as the only acceptable option for at-risk couples to avoid the birth of children with an inherited predisposition to cancer, and to have a healthy child.
"Huntington disease or other neurodegenerative diseases have been successfully applied . PGD has also been performed for familial cancer syndromes including BRCA1, multiple endocrine neoplasia, familial adenomatous polyposis, Li-Fraumeni syndrome, retinoblastoma and von Hippel-Lindau syndrome . For hereditary breast and ovarian cancers caused by mutations in BRCA 1 and 2, the life-time risk of breast cancer for a female carrier may be as high as 85%, her risk of ovarian cancer as high as 60% . "
[Show abstract][Hide abstract] ABSTRACT: Preimplantation genetic diagnosis (PGD) is gradually widely used in prevention of gene diseases and chromosomal abnormalities. Much improvement has been achieved in biopsy technique and molecular diagnosis. Blastocyst biopsy can increase diagnostic accuracy and reduce allele dropout. It is cost-effective and currently plays an important role. Whole genome amplification permits subsequent individual detection of multiple gene loci and screening all 23 pairs of chromosomes. For PGD of chromosomal translocation, fluorescence in-situ hybridization (FISH) is traditionally used, but with technical difficulty. Array comparative genomic hybridization (CGH) can detect translocation and 23 pairs of chromosomes that may replace FISH. Single nucleotide polymorphisms array with haplotyping can further distinguish between normal chromosomes and balanced translocation. PGD may shorten time to conceive and reduce miscarriage for patients with chromosomal translocation. PGD has a potential value for mitochondrial diseases. Preimplantation genetic haplotyping has been applied for unknown mutation sites of single gene disease. Preimplantation genetic screening (PGS) using limited FISH probes in the cleavage-stage embryo did not increase live birth rates for patients with advanced maternal age, unexplained recurrent abortions, and repeated implantation failure. Polar body and blastocyst biopsy may circumvent the problem of mosaicism. PGS using blastocyst biopsy and array CGH is encouraging and merit further studies. Cryopreservation of biopsied blastocysts instead of fresh transfer permits sufficient time for transportation and genetic analysis. Cryopreservation of embryos may avoid ovarian hyperstimulation syndrome and possible suboptimal endometrium.
Clinical and Experimental Reproductive Medicine 09/2011; 38(3):126-34. DOI:10.5653/cerm.2011.38.3.126
"The number of requests for PGD for different genetic applications continues to grow, driving a need for highly technical skills and reliable procedures for any given genetic disorder    . Recently, there has been a trend towards using PGD for adult-onset inherited predispositions   including Alzheimer disease  and familial adenomatous polyposis coli , foreshadowing the potential expansion of PGD to other applications. As the applications for PGD expanded, it developed an application for screening purposes, currently referred to as preimplantation genetic screening. "
[Show abstract][Hide abstract] ABSTRACT: To illuminate and synthesize what is known about the underlying decision making processes surrounding couples' preimplantation genetic diagnosis (PGD) use or disuse and to formulate an initial conceptual framework that can guide future research and practice.
This systematic review targeted empirical studies published in English from 1990 to 2008 that examined the decision making process of couples or individual partners that had used, were eligible for, or had contemplated PGD. Sixteen studies met the eligibility requirements. To provide a more comprehensive review, empirical studies that examined healthcare professionals' perceptions of couples' decision making surrounding PGD use and key publications from a variety of disciplines supplemented the analysis.
The conceptual framework formulated from the review demonstrates that couples' PGD decision making is composed of three iterative and dynamic dimensions: cognitive appraisals, emotional responses, and moral judgments.
Couples think critically about uncertain and probabilistic information, grapple with conflicting emotions, and incorporate moral perspectives into their decision making about whether or not to use PGD.
The quality of care and decisional support for couples who are contemplating PGD use can be improved by incorporating focused questions and discussion from each of the dimensions into counseling sessions.
"Recently, the indication of PGD has been extended to detect hereditary familial cancer syndromes and to avoid passing the cancer gene mutation to offspring (Cram, 2001). By selecting embryos for transfer that are free of genetic predisposition to hereditary cancer syndromes, PGD allows at-risk couples to reproduce a healthy baby (Rechitsky et al., 2002). PGD is of particular value for at-risk couples who would not accept termination of an established pregnancy with an affected fetus. "
[Show abstract][Hide abstract] ABSTRACT: With the progress in cancer genetics and assisted reproductive technologies, it is now possible for cancer gene mutation carriers not only to reduce cancer mortality through the targeting of surveillance and preventive therapies, but also to avoid the birth of at-risk babies through the choice of different means of reproduction. Thus, the incidence of hereditary cancer syndromes may be decreased in the future. The integration of cancer genetic testing and assisted reproductive technologies raises certain ethical, legal and social issues beyond either genetic testing or assisted reproductive technology itself. In this paper, the reproductive decisions/choices of at-risk young couples and the ethical, legal and social concerns of prenatal genetic testing and preimplantation genetic diagnosis for susceptibility to hereditary cancer syndromes are discussed. Specifically, three ethical principles related to the integration of cancer genetic testing and assisted reproductive technologies, i.e. informed choice, beneficence to children and social justice, and their implications for the responsible translation of these medical techniques into common practice of preventive medicine are highlighted.
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