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Yury Verlinsky

Publications and source records attributed to Yury Verlinsky.

At least 19 recordsLinked to original sources
PubMed2006

Multiple micromanipulations for preimplantation genetic diagnosis do not affect embryo development to the blastocyst stage.

To determine the impact of multiple micromanipulation procedures for preimplantation genetic diagnosis (PGD) on embryo development, a retrospective analysis was performed of 9,925 embryos (862 PGD cycles), which were compared with 28,126 nonbiopsied embryos (2,751 consecutive intracytoplasmic sperm injection [ICSI] cycles) from the same time period. Because fertilization rates, the proportion of embryos with > or = 6 cells on day 3, and blastocyst rates were similar in the PGD and control groups, we conclude that multiple micromanipulations on oocytes and embryos can be performed safely for PGD.

Adult↗
PubMed2006

Embryonic stem cells from morula.

It has been shown that it is possible to establish human embryonic stem cell (hESC) lines from morula. Details of the aforementioned injection method of morula under blastocyst are described in this chapter. This chapter also discloses the application of simultaneous staining for two markers, TRA-2-39 and Oct-4, for characteristics of nondifferentiated hESC derived from morula and gives a method. Technical approaches of freezing morula-derived hESC are discussed.

Blastomeres↗
PubMed2006

Preimplantation HLA typing with aneuploidy testing.

Preimplantation HLA typing has been introduced for the treatment of affected siblings, requiring HLA-identical stem cell transplantation. This was applied either in combination with preimplantation genetic diagnosis (PGD) to ensure that the preselected HLA-matched embryos were also free of the genetic disorder, or without PGD, with the only purpose of selecting and transferring the HLA-matched embryos. Because patients requesting preimplantation HLA typing are usually of advanced reproductive age, aneuploidy testing allows not only the avoidance of the birth of children with chromosomal disorders, but also improvement of the reproductive outcome, which is still not sufficiently high in preimplantation HLA typing at the present time. This study presents the results of the first experience of preimplantation HLA typing combined with aneuploidy testing, demonstrating feasibility and impact of aneuploidy testing on the accuracy and outcome of preimplantation HLA typing. Of a total of 138 cycles performed, 87 were combined with PGD and 52 without testing for the causative gene, of which aneuploidy testing was performed in 27 cycles, allowing the preselection and transfer of only those HLA-matched embryos that were also euploid. Although the euploid HLA-identical embryos were available for transfer in only half of these cycles, pregnancy and birth of unaffected HLA-identical children were observed in approximately half of these cycles, suggesting the potential usefulness of incorporating aneuploidy testing into preimplantation HLA typing.

Adult↗
PubMed2006

Reprogramming of human somatic cells by embryonic stem cell cytoplast.

Somatic cell nuclear transfer (SCNT) provides the basis for the development of patient-specific stem cell lines. Recent progress in SCNT suggested the presence of reprogramming factors in human embryonic stem (hES) cells, although no method is currently available for replacement of nuclei of hES cells by somatic cell nuclei. An original technique has been developed, involving the fusion of different types of somatic cells with hES cells, which allowed a complete replacement of the nuclei of hES cells by nuclei of somatic cells. The resulting 'cybrids' were demonstrated to have the genotype of the donor somatic cells and 'stemness' of the recipient hES cells. However, the colonies isolated from the resulting fusion contained a mixture of these cybrid cells with the cells with the recipient nuclei, as well as hybrid cells containing both donor and recipient nuclei, so future purification will be necessary before the technique can be considered for future practical application.

Cell Fusion↗
PubMed2006

Pre-embryonic diagnosis for Sandhoff disease.

Embryos found to be abnormal during preimplantation genetic diagnosis (PGD) are discarded or analysed to confirm the diagnosis. To overcome this limitation, which is unacceptable in some communities and ethnic groups, pre-embryonic genetic diagnosis has been introduced, involving sequential first and second polar body analysis followed by transfer of embryos deriving from the mutation-free oocytes, while removing from culture and freezing the mutant oocytes at the pronuclear stage. The technique is applied here to PGD of Sandhoff disease caused by 16-kb deletion of the hexosaminidase B gene for a couple with a religious objection to discarding embryos irrespective of embryo genotype. Of 16 oocytes tested in a standard IVF protocol for 16-kb deletion, simultaneously with five linked polymorphic markers, eight were predicted mutant and frozen prior to syngamy, with the remaining eight, found to be free of mutation, further cultured and confirmed unaffected using blastomere biopsy. The transfer of two of these embryos resulted in birth of an unaffected child, demonstrating feasibility of pre-embryonic diagnosis to avoid embryo discard.

Adult↗
PubMed2005

Place of preimplantation diagnosis in genetic practice.

Preimplantation genetic diagnosis (PGD) is currently one of the practical options available for couples at-risk to avoid the birth of children with genetic and chromosomal disorders. Despite its novelty, PGD has already become an alternative to traditional prenatal diagnosis, allowing establishing only unaffected pregnancies avoiding the risk for pregnancy termination. Indications for PGD have currently expanded beyond those practices in prenatal diagnosis, such as late-onset diseases with genetic predisposition, and preimplantation HLA typing with the purpose of establishing potential donor progeny for stem cell treatment of siblings, which makes PGD also an important compliment to prenatal diagnosis. The fact that more than 1,000 apparently healthy unaffected children have been born after PGD suggests its accuracy, reliability, and safety. PGD is presently an excellent option for carriers of balanced translocations, and appears to be of special value for avoiding age-related aneuploidies in patients of advanced reproductive age. The accumulated experience of thousands of PGD cycles for poor prognosis in vitro fertilization (IVF) patients provides strong evidence of the improvement of clinical outcome, particularly obvious from the reproductive history of patients. This makes of practical relevance to inform couples at-risk about availability of PGD option, so they make their own choice in avoiding the birth of affected offspring and having healthy children of their own.

Chromosome Disorders↗
PubMed2005

Genetic testing of embryos: a critical need for data.

Preimplantation genetic diagnosis (PGD), the genetic testing of embryos developed through IVF is one of the fastest growing techniques in reproductive medicine and IVF. Some suggest that PGD will become part of every IVF cycle in the future. The growing popularity of PGD has highlighted the fact that there are no comprehensive data available about the use of PGD, its accuracy, or the health outcomes of babies born following PGD. For patients, practitioners, and policymakers alike, such information is critical. To address the gaps in knowledge, a working group of the leading experts in the development and practice of PGD and IVF has begun to design a database to collect information about PGD as practised in the United States.

Databases, Factual↗
PubMed2005

Designing babies: what the future holds.

Advances in reproductive technology have opened new opportunities to avoid inherited diseases in offspring. The preimplantation genetic diagnosis (PGD) of human embryos permits those embryos carrying gene disorders or a non-diploid chromosome constitution to be identified. Numerous disease genes including those with a late onset have been identified and the conditions averted in children. Risks of abortion have been reduced, and the incidence of live births raised after PGD. It is also possible to select embryos with human leukocyte antigens (HLA) identical to those of a sick elder sibling, and then use stem cells from cord blood at birth to supply the necessary therapy. This form of treatment has alleviated the inherited disease in many recipients. The outlook and ethics of this approach to the alleviation of human disorders are discussed.

Ethics, Medical↗
PubMed2005

Preimplantation diagnosis: a realistic option for assisted reproduction and genetic practice.

PURPOSE OF REVIEW: Preimplantation genetic diagnosis (PGD) allows genetically disadvantaged couples to reproduce, while avoiding the birth of children with targeted genetic disorders. By ensuring unaffected pregnancies, PGD circumvents the possible need and therefore risks of pregnancy termination. This review will describe the current progress of PGD for Mendelian and chromosomal disorders and its impact on reproductive medicine. RECENT FINDINGS: Indications for PGD have expanded beyond those used in prenatal diagnosis, which has also resulted in improved access to HLA-compatible stem-cell transplantation for siblings through preimplantation HLA typing. More than 1000 apparently healthy, unaffected children have been born after PGD, suggesting its accuracy, reliability and safety. PGD is currently the only hope for carriers of balanced translocations. It also appears to be of special value for avoiding age-related aneuploidies in in-vitro fertilization patients who have a particularly poor prognosis for a successful pregnancy; the accumulated experience of thousands of PGD cycles strongly suggests that PGD can improve clinical outcome for such patients. SUMMARY: PGD would particularly benefit poor prognosis in-vitro fertilization patients and other at-risk couples by improving reproductive outcomes and avoiding the birth of affected offspring.

Chromosome Aberrations↗
PubMed2005

Preimplantation genetics: Improving access to stem cell therapy.

There has been progress in the application of stem cell transplantation for treatment of an increasing number of severe congenital and acquired bone marrow disorders, currently restricted by the availability of human leukocyte antigen (HLA)-matched related donors. Preimplantation HLA typing has recently been introduced to improve the access to stem cell therapy for inherited bone marrow failures. Preimplantation genetic diagnosis (PGD) provides an option not only for avoiding an affected pregnancy with thalassemia and other inherited disorders but also for preselection of the HLA-compatible donors for affected siblings. Multiple short tandem repeat markers throughout the HLA region are applied for this purpose, allowing 100% accuracy of HLA typing, through picking up possible recombination in the HLA region, as well as the copy number of chromosome 6, which affect accuracy of preimplantation HLA typing. Present experience of preimplantation HLA typing includes preimplantation HLA typing in 180 cycles, 122 of which were done as part of PGD for Fanconi anemia, thalassemia, Wiscott-Aldrich syndrome, hyper-immunoglobulin M syndrome, hypohidrotic ectodermal dysplasia with immune deficiency, and X-linked adrenoleukodystrophy, and 58 for the sole purpose of HLA typing for leukemias and for aplastic and Diamond-Blackfan anemia. The applied method resulted in the accurate preselection and transfer of 100% HLA-matched embryos, yielding already three dozen clinical pregnancies and the birth of two dozen HLA-matched children to the siblings requiring stem cell transplantation. Successful therapy with HLA-matched stem cells, obtained from these PGD children, has been achieved already for Diamond-Blackfan anemia hypohidrotic ectodermal dysplasia with immune deficiency and thalassemia.

Anemia, Diamond-Blackfan↗
PubMed2005

Preimplantation genetic diagnosis in assisted reproduction.

Despite its novelty, preimplantation genetic diagnosis has become an alternative to traditional prenatal diagnosis, allowing the establishment of only unaffected pregnancies and avoiding the risk of pregnancy termination. In addition, preimplantation genetic diagnosis is presently applied for much wider indications than prenatal diagnosis, including common diseases with genetic predisposition and preimplantation human leukocyte antigen typing, with the purpose of establishing potential donor progeny for stem cell treatment of siblings. Many hundreds of apparently healthy, unaffected children have been born after preimplantation genetic diagnosis, presenting evidence of its accuracy, reliability and safety. Preimplantation genetic diagnosis appears to be of special value for avoiding age-related aneuploidies in patients of advanced reproductive age, improving reproductive outcome, particularly obvious from their reproductive history, and is presently an extremely attractive option for carriers of balanced translocations to have unaffected children of their own.

Embryo, Mammalian↗
PubMed2004

Preimplantation HLA testing.

CONTEXT: Preimplantation genetic diagnosis (PGD) has become an option for couples for whom termination of an affected pregnancy identified by traditional prenatal diagnosis is unacceptable and is applicable to indications beyond those of prenatal diagnosis, such as HLA matching to affected siblings to provide stem cell transplantation. OBJECTIVE: To describe preimplantation HLA typing, not involving identification of a causative gene, for couples who had children with bone marrow disorders at need for HLA-matched stem cell transplantation. DESIGN, SETTING, AND PARTICIPANTS: HLA matching procedures conducted at a single site during 2002-2003 in an in vitro fertilization program for 9 couples with children affected by acute lymphoid leukemia, acute myeloid leukemia, or Diamond-Blackfan anemia requiring HLA-matched stem cell transplantation. In 13 clinical cycles, DNA in single blastomeres removed from 8-cell embryos following in vitro fertilization was analyzed for HLA genes simultaneously with analysis for short tandem repeats in the HLA region to select and transfer only those embryos that were HLA matched to affected siblings. MAIN OUTCOME MEASURES: Results of HLA matching and pregnancy outcome. RESULTS: As a result of testing a total of 199 embryos, 45 (23%) HLA-matched embryos were selected, of which 28 were transferred in 12 clinical cycles, resulting in 5 singleton pregnancies and birth of 5 HLA-matched healthy children. CONCLUSION: This is the first known experience of preimplantation HLA typing performed without PGD for a causative gene, providing couples with a realistic option of having HLA-matched offspring to serve as potential donors of stem cells for their affected siblings.

Anemia, Diamond-Blackfan↗
PubMed2004

Over a decade of experience with preimplantation genetic diagnosis: a multicenter report.

OBJECTIVE: To review a 12-year experience of the world's three largest preimplantation genetic diagnosis (PGD) centers. DESIGN: Multicenter analysis of the clinical outcome of PGD. SETTING: In vitro fertilization programs at the Reproductive Genetics Institute, Chicago, Illinois; Saint Barnabas Medical Center, West Orange, New Jersey; and SISMER, Bologna, Italy. PATIENT(S): Poor-prognosis IVF patients, patients carrying balanced chromosomal translocations, and couples at risk for producing children with Mendelian disorders. INTERVENTION(S): In vitro fertilization, intracytoplasmic sperm injection, polar body removal, blastomere biopsy, and ET. MAIN OUTCOME MEASURE(S): DNA or chromosomal analysis of biopsied polar bodies or blastomeres, implantation and clinical pregnancy rates, and live-born pregnancy outcome. RESULT(S): A total of 754 babies have been born as a result of 4,748 PGD attempts, which shows the expanded application and the practical relevance of PGD for single-gene disorders, chromosomal aneuploidies and translocations, late-onset diseases with genetic predisposition, and nondisease testing in couples at need for human leukocyte antigens-matched offspring for treatment of affected siblings. CONCLUSION(S): Preimplantation genetic diagnosis is evolving to become a clinical option for couples at risk for producing offspring with Mendelian diseases, has a positive numerical impact in standard assisted reproduction practices through aneuploidy testing, and reduces by at least fourfold the spontaneous abortion rate in couples carrying translocations.

Blastula↗
PubMed2004

Over a decade of experience with preimplantation genetic diagnosis.

The three respondents provide additional support for preimplantation genetic diagnosis (PGD) having the pivotal place it now has in prenatal genetic diagnosis: chromosomal abnormalities (e.g., unbalanced translocations), Mendelian disorders, and HLA typing for transfer of compatible, genetically normal, embryos. Transferring euploid embryos has decreased the clinical abortion rate and increased the implantation rate in assisted reproductive technologies (ART), but it has not necessarily improved the live-birth rate. Safer embryo biopsy, more extensive diagnostic efforts (i.e., microarray analysis), and more refined patient selection may be required before shifting from preselection of embryos based solely on morphological parameters to transfer of only aneuploidy-free embryos.

Abortion, Spontaneous↗
PubMed2004

Preimplantation genetic diagnosis for polycystic kidney disease.

OBJECTIVE: To use preimplantation genetic diagnosis for achieving a polycystic kidney disease (PKD)-free pregnancy for a couple in which the female partner was affected by PKD but whose PKD1 or PKD2 carrier status was not established. DESIGN: Case report. SETTING: The IVF program of Reproductive Genetics Institute, Chicago, Illinois. PATIENT(S): An at-risk couple with the female partner affected by PKD, whose PKD1 or PKD2 carrier status was not established. INTERVENTION(S): Removal of PB1 and PB2 and testing for three closely linked markers to PKD1 (Kg8, D16S664, and SM7) and four closely linked markers to PKD2 (D4S2922, D4S2458, D4S423, and D4S1557) after standard IVF. MAIN OUTCOME MEASURE(S): Deoxyribonucleic acid analysis of PB1 and PB2 indicating whether corresponding oocytes were PKD1 or PKD2 allele free, for the purpose of transferring only embryos resulting from mutation-free oocytes. RESULT(S): Of 11 oocytes tested by PB1 and PB2 DNA analysis, 7 were predicted to contain PKD1 or PKD2, with the remaining 4 free of both mutations. Three embryos resulting from these oocytes were transferred, yielding a twin pregnancy and the birth of two unaffected children. CONCLUSION(S): This is the first preimplantation genetic diagnosis for PKD, which resulted in the birth of healthy twins confirmed to be free of PKD1 and PKD2. Preimplantation genetic diagnosis based on linked marker analysis provides an alternative for avoiding the pregnancy and birth of children with PKD, even in at-risk couples without exact PKD1 or PKD2 carrier information.

Chromosome Mapping↗
PubMed2004

Thirteen years' experience of preimplantation diagnosis: report of the Fifth International Symposium on Preimplantation Genetics.

Preimplantation genetic diagnosis (PGD) has been further developed into a practical option for avoiding the birth of affected children, representing an important complement to traditional prenatal diagnosis. More than 1000 unaffected children have been born after PGD, suggesting the accuracy and safety of the procedure, which is currently also used with the establishment of potential donor progeny for stem cell treatment of siblings. Together with progress in the establishment of embryonic stem (ES) cells, this may contribute to the development and application of stem cell therapy. The accumulated experience of thousands of PGD cycles for poor prognosis IVF patients provides further evidence of the improvement of clinical outcome, particularly obvious from the reproductive history of PGD patients. A high prevalence of aneuploidies in oocytes and embryos may affect the accuracy of PGD for single gene disorders, making aneuploidy testing an important part of PGD for causative genes and preimplantation human leukocyte antigen (HLA) typing. A sequential sampling of both oocytes and the resulting embryos may improve accuracy of aneuploidy testing and may also allow the detection and avoidance of transfer of embryos with uniparental disomies. Current developments and application of nuclear transfer and sperm duplication techniques, and microarray technology, may also contribute to the improvement of PGD and help in the development of PGD for genetic expression disorders.

Female↗