The Experts below are selected from a list of 4209 Experts worldwide ranked by ideXlab platform
Svetlana Rechitsky - One of the best experts on this subject based on the ideXlab platform.
-
first systematic experience of Preimplantation Genetic Diagnosis for single gene disorders and or Preimplantation human leukocyte antigen typing combined with 24 chromosome aneuploidy testing
2015Co-Authors: Svetlana Rechitsky, T Pakhalchuk, Geraldine San Ramos, Adam Goodman, Zev Zlatopolsky, Anver KulievAbstract:Objective To study the feasibility, accuracy, and reproductive outcome of 24-chromosome aneuploidy testing (24-AT), combined with Preimplantation Genetic Diagnosis (PGD) for single-gene disorders (SGDs) or human leukocyte antigen (HLA) typing in the same biopsy sample. Design Retrospective study. Setting Preimplantation Genetic Diagnosis center. Patient(s) A total of 238 PGD patients, average age 36.8 years, for whom 317 combined PGD cycles were performed, involving 105 different conditions, with or without HLA typing. Intervention(s) Whole-genome amplification product, obtained in 24-AT, was used for PGD and/or HLA typing in the same blastomere or blastocyst biopsy samples. Main Outcome Measure(s) Proportion of the embryos suitable for transfer detected in these blastomere or blastocyst samples, and the resulting pregnancy and spontaneous abortion rates. Result(s) Embryos suitable for transfer were detected in 42% blastocyst and 25.1% blastomere samples, with a total of 280 unaffected, HLA-matched euploid embryos detected for transfer in 212 cycles (1.3 embryos per transfer), resulting in 145 (68.4%) unaffected pregnancies and birth of 149 healthy, HLA-matched children. This outcome is significantly different from that of our 2,064 PGD cycle series without concomitant 24-AT, including improved pregnancy (68.4% vs. 45.4%) and 3-fold spontaneous abortion reduction (5.5% vs. 15%) rates. Conclusion(s) The introduced combined approach is a potential universal PGD test, which in addition to achieving extremely high diagnostic accuracy, significantly improves reproductive outcomes of PGD for SGDs and HLA typing in patients of advanced reproductive age.
-
Preimplantation Genetic Diagnosis pgd for Genetic prion disorder due to f198s mutation in the prnp gene
2014Co-Authors: Alice Uflacker, Svetlana Rechitsky, Murali P Doraiswamy, Tricia See, Michael D Geschwind, Ilan TurkaspaAbstract:Importance To describe the first case of Preimplantation Genetic Diagnosis (PGD) and in vitro fertilization (IVF) performed for the prevention of Genetic prion disease in the children of a 27-year-old asymptomatic woman with a family history of Gerstmann-Straussler-Sheinker syndrome (GSS). Observations PGD and fertilization cycles resulted in detection of 6 F198S mutation-free embryos. Of these, 2 were selected for embryo transfer to the patient’s uterus, yielding a clinical twin pregnancy and birth of healthy but slightly premature offspring with normal development at age 27 months. Conclusion and Relevance IVF with PGD is a viable option for couples who wish to avoid passing the disease to their offspring. Neurologists should be aware of PGD to be able to better consult at-risk families on their reproductive choices.
-
polar body based Preimplantation Genetic Diagnosis for mendelian disorders
2011Co-Authors: Anver Kuliev, Svetlana RechitskyAbstract:Introduced >20 years ago, the use of polar bodies (PBs), involving sequential removal and Genetic analysis of the first (PBI) and second (PB2) PB, provides the option for pre-embryonic Diagnosis, when the objection to the embryo biopsy procedures makes Preimplantation Genetic Diagnosis (PGD) non-applicable. PB-based approach has presently been utilized in PGD for Genetic and chromosomal disorders, applied either separately, or together with embryo biopsy approaches, especially if there are two or more PGD indications. We present here the world's largest experience of 938 PGD cycles for single-gene disorders performed by PB testing for 146 different monogenic conditions, which resulted in the birth of 345 healthy children (eight pregnancies are still ongoing), providing strong evidence that PB-based PGD is a reliable and safe procedure, with an extremely high accuracy rate of over 99%. With application of microarray technology, PB-based approach will be utilized for increasing number of indications, involving simultaneous testing for 24 chromosomes and single-gene disorders.
-
single gene testing combined with single nucleotide polymorphism microarray Preimplantation Genetic Diagnosis for aneuploidy a novel approach in optimizing pregnancy outcome
2011Co-Authors: Paul R Brezina, Anver Kuliev, Svetlana Rechitsky, A T Benner, Ekaterina Pomerantseva, Dana Pauling, W G KearnsAbstract:Objective To describe a method of amplifying DNA from blastocyst trophectoderm cells (two or three cells) and simultaneously performing 23-chromosome single nucleotide polymorphism microarrays and single-gene Preimplantation Genetic Diagnosis. Design Case report. Setting IVF clinic and Preimplantation Genetic diagnostic centers. Patient(s) A 36-year-old woman, gravida 2, para 1011, and her husband who both were carriers of GM 1 gangliosidosis. The couple wished to proceed with microarray analysis for aneuploidy detection coupled with DNA sequencing for GM 1 gangliosidosis. Intervention(s) An IVF cycle was performed. Ten blastocyst-stage embryos underwent trophectoderm biopsy. Twenty-three–chromosome microarray analysis for aneuploidy and specific DNA sequencing for GM 1 gangliosidosis mutations were performed. Main Outcome Measure(s) Viable pregnancy. Result(s) After testing, elective single embryo transfer was performed followed by an intrauterine pregnancy with documented fetal cardiac activity by ultrasound. Conclusion(s) Twenty-three–chromosome microarray analysis for aneuploidy detection and single-gene evaluation via specific DNA sequencing and linkage analysis are used for Preimplantation Diagnosis for single-gene disorders and aneuploidy. Because of the minimal amount of Genetic material obtained from the day 3 to 5 embryos (up to 6 pg), these modalities have been used in isolation of each other. The use of Preimplantation Genetic Diagnosis for aneuploidy coupled with testing for single-gene disorders via trophectoderm biopsy is a novel approach to maximize pregnancy outcomes. Although further investigation is warranted, Preimplantation Genetic Diagnosis for aneuploidy and single-gene testing seem destined to be used increasingly to optimize ultimate pregnancy success.
-
Preimplantation Genetic Diagnosis with hla matching
2004Co-Authors: Svetlana Rechitsky, Anver Kuliev, Ilan Turkaspa, Randy Morris, Yury VerlinskyAbstract:Abstract Preimplantation Genetic Diagnosis (PGD) has recently been offered in combination with HLA typing, which allowed a successful haematopoietic reconstitution in affected siblings with Fanconi anaemia by transplantation of stem cells obtained from the HLA-matched offspring resulting from PGD. This study presents the results of the first PGD practical experience performed in a group of couples at risk for producing children with Genetic disorders. These parents also requested Preimplantation HLA typing for treating the affected children in the family, who required HLA-matched stem cell transplantation. Using a standard IVF procedure, oocytes or embryos were tested for causative gene mutations simultaneously with HLA alleles, selecting and transferring only those unaffected embryos, which were HLA matched to the affected siblings. The procedure was performed for patients with children affected by Fanconi anaemia (FANC) A and C, different thalassaemia mutations, Wiscott–Aldrich syndrome, X-linked adrenoleukodystrophy, X-linked hyper-immunoglobulin M syndrome and X-linked hypohidrotic ectodermal displasia with immune deficiency. Overall, 46 PGD cycles were performed for 26 couples, resulting in selection and transfer of 50 unaffected HLA-matched embryos in 33 cycles, yielding six HLA-matched clinical pregnancies and the birth of five unaffected HLA-matched children. Despite the controversy of PGD use for HLA typing, the data demonstrate the usefulness of this approach for at-risk couples, not only to avoid the birth of affected children with an inherited disease, but also for having unaffected children who may also be potential HLA-matched donors of stem cells for treatment of affected siblings.
Anver Kuliev - One of the best experts on this subject based on the ideXlab platform.
-
first systematic experience of Preimplantation Genetic Diagnosis for single gene disorders and or Preimplantation human leukocyte antigen typing combined with 24 chromosome aneuploidy testing
2015Co-Authors: Svetlana Rechitsky, T Pakhalchuk, Geraldine San Ramos, Adam Goodman, Zev Zlatopolsky, Anver KulievAbstract:Objective To study the feasibility, accuracy, and reproductive outcome of 24-chromosome aneuploidy testing (24-AT), combined with Preimplantation Genetic Diagnosis (PGD) for single-gene disorders (SGDs) or human leukocyte antigen (HLA) typing in the same biopsy sample. Design Retrospective study. Setting Preimplantation Genetic Diagnosis center. Patient(s) A total of 238 PGD patients, average age 36.8 years, for whom 317 combined PGD cycles were performed, involving 105 different conditions, with or without HLA typing. Intervention(s) Whole-genome amplification product, obtained in 24-AT, was used for PGD and/or HLA typing in the same blastomere or blastocyst biopsy samples. Main Outcome Measure(s) Proportion of the embryos suitable for transfer detected in these blastomere or blastocyst samples, and the resulting pregnancy and spontaneous abortion rates. Result(s) Embryos suitable for transfer were detected in 42% blastocyst and 25.1% blastomere samples, with a total of 280 unaffected, HLA-matched euploid embryos detected for transfer in 212 cycles (1.3 embryos per transfer), resulting in 145 (68.4%) unaffected pregnancies and birth of 149 healthy, HLA-matched children. This outcome is significantly different from that of our 2,064 PGD cycle series without concomitant 24-AT, including improved pregnancy (68.4% vs. 45.4%) and 3-fold spontaneous abortion reduction (5.5% vs. 15%) rates. Conclusion(s) The introduced combined approach is a potential universal PGD test, which in addition to achieving extremely high diagnostic accuracy, significantly improves reproductive outcomes of PGD for SGDs and HLA typing in patients of advanced reproductive age.
-
polar body based Preimplantation Genetic Diagnosis for mendelian disorders
2011Co-Authors: Anver Kuliev, Svetlana RechitskyAbstract:Introduced >20 years ago, the use of polar bodies (PBs), involving sequential removal and Genetic analysis of the first (PBI) and second (PB2) PB, provides the option for pre-embryonic Diagnosis, when the objection to the embryo biopsy procedures makes Preimplantation Genetic Diagnosis (PGD) non-applicable. PB-based approach has presently been utilized in PGD for Genetic and chromosomal disorders, applied either separately, or together with embryo biopsy approaches, especially if there are two or more PGD indications. We present here the world's largest experience of 938 PGD cycles for single-gene disorders performed by PB testing for 146 different monogenic conditions, which resulted in the birth of 345 healthy children (eight pregnancies are still ongoing), providing strong evidence that PB-based PGD is a reliable and safe procedure, with an extremely high accuracy rate of over 99%. With application of microarray technology, PB-based approach will be utilized for increasing number of indications, involving simultaneous testing for 24 chromosomes and single-gene disorders.
-
single gene testing combined with single nucleotide polymorphism microarray Preimplantation Genetic Diagnosis for aneuploidy a novel approach in optimizing pregnancy outcome
2011Co-Authors: Paul R Brezina, Anver Kuliev, Svetlana Rechitsky, A T Benner, Ekaterina Pomerantseva, Dana Pauling, W G KearnsAbstract:Objective To describe a method of amplifying DNA from blastocyst trophectoderm cells (two or three cells) and simultaneously performing 23-chromosome single nucleotide polymorphism microarrays and single-gene Preimplantation Genetic Diagnosis. Design Case report. Setting IVF clinic and Preimplantation Genetic diagnostic centers. Patient(s) A 36-year-old woman, gravida 2, para 1011, and her husband who both were carriers of GM 1 gangliosidosis. The couple wished to proceed with microarray analysis for aneuploidy detection coupled with DNA sequencing for GM 1 gangliosidosis. Intervention(s) An IVF cycle was performed. Ten blastocyst-stage embryos underwent trophectoderm biopsy. Twenty-three–chromosome microarray analysis for aneuploidy and specific DNA sequencing for GM 1 gangliosidosis mutations were performed. Main Outcome Measure(s) Viable pregnancy. Result(s) After testing, elective single embryo transfer was performed followed by an intrauterine pregnancy with documented fetal cardiac activity by ultrasound. Conclusion(s) Twenty-three–chromosome microarray analysis for aneuploidy detection and single-gene evaluation via specific DNA sequencing and linkage analysis are used for Preimplantation Diagnosis for single-gene disorders and aneuploidy. Because of the minimal amount of Genetic material obtained from the day 3 to 5 embryos (up to 6 pg), these modalities have been used in isolation of each other. The use of Preimplantation Genetic Diagnosis for aneuploidy coupled with testing for single-gene disorders via trophectoderm biopsy is a novel approach to maximize pregnancy outcomes. Although further investigation is warranted, Preimplantation Genetic Diagnosis for aneuploidy and single-gene testing seem destined to be used increasingly to optimize ultimate pregnancy success.
-
over a decade of experience with Preimplantation Genetic Diagnosis
2004Co-Authors: Yury Verlinsky, Santiago Munné, Jacques Cohen, Joe Leigh Simpson, Luca Gianaroli, A P Ferraretti, Anver KulievAbstract: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.
-
over a decade of experience with Preimplantation Genetic Diagnosis a multicenter report
2004Co-Authors: Yury Verlinsky, Santiago Munné, Jacques Cohen, Joe Leigh Simpson, Luca Gianaroli, A P Ferraretti, Anver KulievAbstract:Abstract 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.
Santiago Munné - One of the best experts on this subject based on the ideXlab platform.
-
technology requirements for Preimplantation Genetic Diagnosis to improve assisted reproduction outcomes
2010Co-Authors: Santiago Munné, Dagan Wells, Jacques CohenAbstract:Preimplantation Genetic Diagnosis has been proposed as a method to improve assisted reproduction technology outcomes, but different techniques have produced conflicting results. The use of appropriate techniques may provide positive outcomes.
-
Preimplantation Genetic Diagnosis pgd improves pregnancy outcome for translocation carriers with a history of recurrent losses
2010Co-Authors: J Fischer, P Colls, T Escudero, Santiago MunnéAbstract:OBJECTIVE: To determine if Preimplantation Genetic Diagnosis (PGD) for translocation carriers with three or more pregnancy losses reduces loss rates. DESIGN: Retrospective review of data. SETTING: Preimplantation Genetic Diagnosis laboratory servicing IVF groups. PATIENT(S): Patients (n = 192) undergoing PGD for either a reciprocal translocation or Robertsonian translocation who had three or more previous pregnancy losses. INTERVENTION(S): Preimplantation Genetic Diagnosis for translocations. MAIN OUTCOME MEASURE(S): Pregnancy loss rate, pregnancy success rate defined as delivery of at least one child or an ongoing pregnancy in the third trimester, and length of time to success. RESULT(S): Pregnancy loss rate was significantly reduced to 13% post-PGD compared with 88.5% in previous non-PGD pregnancies and to 35% to 64% from naturally conceived pregnancies as reported in the literature. Pregnancy success rate was 87%. Conception occurred after an average of 1.4 cycles or <4 months. CONCLUSION(S): Individuals with translocations who have experienced three or more losses benefit from PGD by realizing a significant reduction in loss rate and improvement in rate of success of pregnancy. Length of time to conceive is also dramatically reduced compared with data in the literature for similar populations not undergoing PGD.
-
Preimplantation Genetic Diagnosis of single gene disorders experience with more than 200 cycles conducted by a reference laboratory in the united states
2009Co-Authors: C Gutierrezmateo, Santiago Munné, Jacques Cohen, J Fischer, Jorge F Sanchezgarcia, S Tormasi, Dagan WellsAbstract:Objective To evaluate trends and outcomes from Preimplantation Genetic Diagnosis (PGD) cycles. Design Retrospective data review. Setting A reference laboratory specializing in the provision of PGD services. Patient(s) One hundred sixty-two patients at risk of transmitting a serious monogenic disorder to their children. Intervention(s) In vitro fertilization and PGD. Main Outcome Measure(s) Results of PGD cycles. Result(s) Two hundred twenty-four PGD cycles were referred by 59 different IVF centers. Forty-six different disorders were diagnosed, including several not previously diagnosed at the Preimplantation stage. Cystic fibrosis was the most common reason for referral (73 cases). A Diagnosis was obtained for 84.4% of tested embryos, with results available 6 to 36 hours from sample receipt. Only 10.7% of cycles had no transfer. The pregnancy rate per cycle with ET was 43.4%. Conclusion(s) Unlike previous reports of multiple PGD cycles, all of the cases in this study involved shipping of biopsied cells to a specialist reference laboratory for Diagnosis. This approach, sometimes referred to as "transport PGD," accounts for the vast majority of PGD cycles in the United States. Preimplantation Genetic Diagnosis was shown to be an effective alternative to prenatal Diagnosis for patients with an ethical or a religious objection to pregnancy termination and for infertile patients carrying a Genetic disorder. Demand for this service at our center doubled in each of the last 4 years. Pregnancy rates per ET were encouraging, almost half of all patients undergoing their first PGD cycle achieving a birth or ongoing pregnancy.
-
effect of infertility maternal age and number of previous miscarriages on the outcome of Preimplantation Genetic Diagnosis for idiopathic recurrent pregnancy loss
2009Co-Authors: John Garrisi, K.m. Ferry, P Colls, Xhezong Zheng, Margarett G Garrisi, Santiago MunnéAbstract:Objective To determine whether Preimplantation Genetic Diagnosis (PGD) would decrease spontaneous abortion rates in patients with idiopathic recurrent pregnancy loss (RPL). Design Controlled clinical study. Setting IVF center and PGD reference laboratory. Patient(s) Patients with RPL with no known etiology. Intervention(s) Preimplantation Genetic Diagnosis by fluorescence in situ hybridization analyzing nine chromosomes. Main Outcome Measure(s) The spontaneous abortion rate after PGD was compared to the patients' own expected risk of abortion. Patients were evaluated according to the number of previous losses, fertility, and maternal age. Result(s) Preimplantation Genetic Diagnosis significantly reduced spontaneous abortions in patients with RPL, especially for patients with more than two previous losses (12.8% vs. 35.9% expected). The PGD significantly reduced the rate of spontaneous abortion in both fertile (15.2% vs. 33.8% expected) and infertile patients (13.0% vs. 29.5%), which also achieved similar delivery rates (37% and 34%, respectively). The beneficial effect of PGD was less pronounced in patients Conclusion(s) Preimplantation Genetic Diagnosis improves pregnancy outcome for women with idiopathic RPL, especially those with more than two previous losses, and >35 years of age, and that improvement is not affected by fertility status.
-
over a decade of experience with Preimplantation Genetic Diagnosis
2004Co-Authors: Yury Verlinsky, Santiago Munné, Jacques Cohen, Joe Leigh Simpson, Luca Gianaroli, A P Ferraretti, Anver KulievAbstract: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.
Richard T. Scott - One of the best experts on this subject based on the ideXlab platform.
-
evaluation of targeted next generation sequencing based Preimplantation Genetic Diagnosis of monogenic disease
2013Co-Authors: Nathan R. Treff, Anastasia Fedick, X Tao, Batsal Devkota, Deanne Taylor, Richard T. ScottAbstract:Objective To investigate the applicability of next-generation sequencing (NGS) to Preimplantation Genetic Diagnosis (PGD); to evaluate semiconductor-based NGS for Genetic analysis of human embryos. Design Blinded. Setting Academic center for reproductive medicine. Patient(s) Six couples at risk of transmitting single-gene disorders to their offspring. Intervention(s) None. Main Outcome Measure(s) Embryonic genotype consistency of NGS with two independent conventional methods of PGD. Result(s) NGS provided 100% equivalent PGD diagnoses of compound point mutations and small deletions and insertions compared with both reference laboratory– and internally developed quantitative polymerase chain reaction (qPCR)–based analyses. Furthermore, NGS single-gene disorder screening could be performed in parallel with qPCR-based comprehensive chromosome screening. Conclusion(s) NGS can provide blastocyst PGD results with a high level of consistency with established methodologies. This study and its design could serve as a model for further development of this important and emerging technology.
-
Blastocyst Preimplantation Genetic Diagnosis (PGD) of a mitochondrial DNA disorder
2012Co-Authors: Nathan R. Treff, J. Campos, Xin Tao, Brynn Levy, K.m. Ferry, Richard T. ScottAbstract:Objective To evaluate the utility of trophectoderm biopsy for Preimplantation Genetic Diagnosis (PGD) of mitochondrial (mt) DNA mutation load. Design A PGD case and analysis of blastocyst mosaicism. Setting Academic center for reproductive medicine. Patient(s) A 30-year-old carrier of 35% 3243A>G mtDNA mutation load with a daughter affected by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Intervention(s) Blastocyst biopsy for PGD of mutation load and gender. Main Outcome Measure(s) Variation in mutation load within and among embryos, and newborn mutation load after PGD-based selection. Result(s) Oocytes and embryos were found to possess a variety of 3243A>G mutation loads from 9% to 90% in oocytes and 7% to 91% in embryos, demonstrating that PGD would be a relevant procedure. Highly consistent results were obtained within multiple biopsies of both cleavage- and blastocyst-stage embryos. Importantly, mutation loads observed in trophectoderm were predictive of the inner cell mass ( r 2 = 0.97). Transfer of a male embryo, predicted to possess 12% mutation load by analysis of a trophectoderm biopsy, resulted in the delivery of a boy with tissue-specific mutation loads ranging from undetectable to 15%. Conclusion(s) This study represents the first successful clinical application of PGD to reduce the transgenerational risk of transmitting an mtDNA disorder and supports the applicability of blastocyst trophectoderm PGD for carriers of mtDNA mutations attempting reproduction.
-
Trophectoderm biopsy for single-gene disorder Preimplantation Genetic Diagnosis (PGD) is significantly more reliable than day 3 blastomere biopsy
2011Co-Authors: Eric J. Forman, K.m. Ferry, N.-a. Gueye, R.d. Smith, John R. Stevens, Richard T. ScottAbstract:TROPHECTODERM BIOPSY FOR SINGLE-GENE DISORDER Preimplantation Genetic Diagnosis (PGD) IS SIGNIFICANTLYMORE RELIABLE THAN DAY 3 BLASTOMERE BIOPSY. E. J. Forman, K. M. Ferry, N.-A. Gueye, R. D. Smith, J. Stevens, R. T. Scott, Jr. Reproductive Endocrinology & Infertility, Reproductive Medicine Associates of New Jersey, Morristown, NJ; Obstetrics, Gynecology and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ; Fertility Laboratories of Colorado, Lone Tree, CO.
Gheona Altarescu - One of the best experts on this subject based on the ideXlab platform.
-
Preimplantation Genetic Diagnosis for fetal neonatal alloimmune thrombocytopenia due to antihuman platelet antigen maternal antibodies
2012Co-Authors: Gheona Altarescu, Ephrat Levylahad, Ehud J. Margalioth, Eldar T Geva, Sorina Grisarugranovsky, Lilach Bonstein, Hagit Miskin, Irit Varshver, Paul RenbaumAbstract:OBJECTIVE To develop a reliable Preimplantation Genetic Diagnosis protocol for antihuman platelet antigen-1 incompatibility for a family in whom antenatal treatment was not possible because of the mother's hypersensitivity to intravenous immunoglobulin (IVIG). METHODS Haplotypes were constructed from genomic DNA of the family members. A polymerase chain reaction protocol that included eight microsatellite polymorphic markers and the ITGB3-specific (T196C, rs5918) polymorphism were multiplexed to be used in a single cell protocol, and single blastomeres were analyzed. RESULTS In one Preimplantation Genetic Diagnosis cycle, out of 28 retrieved oocytes, 24 embryos fertilized and 12 underwent biopsy. Three embryos were found to be antihuman platelet antigen-1b/1b homozygotes and two were transferred. This cycle resulted in an uneventful pregnancy and birth of a healthy child. CONCLUSION In cases in which there is antihuman platelet antigen incompatibility and IVIG cannot be administered, Preimplantation Genetic Diagnosis is a reliable alternative to enable birth of unaffected children.
-
successful polar body based Preimplantation Genetic Diagnosis for achondroplasia
2008Co-Authors: Paul Renbaum, Talia Eldargeva, Gheona Altarescu, Ephrat Levylahad, Ehud J. Margalioth, Ben A Chetrit, G MunterAbstract:Achondroplasia, the most common form of dwarfism, is a candidate for Preimplantation Genetic Diagnosis (PGD) because a single mutation accounts for almost all cases. Multiplex fluorescent assay including the common G380R mutation in the FGFR3 gene and eight close polymorphic markers was developed. First and second polar bodies (PB) were used for PGD analysis. An affected woman was treated with routine long-protocol ovarian stimulation and puncture. In the first PGD cycle, out of four fertilized oocytes, PB analysis revealed two mutant oocytes, one with total amplification failure of the maternal allele and one with inconclusive results. In the second PGD cycle, 14 oocytes were retrieved following a higher FSH dose and by performing oocyte retrieval and by placing the patient in the anti-Trendelenburg position using abdominal pressure to allow all follicles to be drained. Following PB analysis, two embryos containing the wild-type FGFR3 allele were transferred. This led to an uncomplicated pregnancy and delivery by Caesarean section at week 38 of a healthy boy, carrying the FGFR3 wild-type maternal allele. In conclusion, oocyte retrieval, while difficult in patients with achondroplasia, can be successfully performed. PB analysis is a reliable and sensitive method for PGD for maternal achondroplasia.
-
advantages of multiple markers and polar body analysis in Preimplantation Genetic Diagnosis for alagille disease
2007Co-Authors: Paul Renbaum, Y Kaplan, Talia Eldargeva, Baruch Brooks, Ephrat Levylahad, Ehud J. Margalioth, Gheona AltarescuAbstract:Objective The development of a Preimplantation Genetic Diagnosis (PGD) protocol for Alagille syndrome (AGS), a rare autosomal dominant disorder with hepatic, cardiac and ophthalmologic involvement. Methods We developed a polar body (PB)-based multiplex fluorescent PCR reaction for a female affected with AGS. The protocol included analysis of the Jagged 1 (JAG1) familial mutation and five closely linked highly polymorphic markers (D20S162, D20S901, D20S894, and D20S186). Results In two cycles of PGD 9 of ten embryos were accurately diagnosed by assessment of first and second PBs, one embryo required additional blastomere biopsy. Conclusions This protocol takes advantage of the larger window of opportunity for transfer and the increased accuracy of Diagnosis afforded by the combination of PB biopsy and multiple marker analysis. Two cycles resulted in the transfer of two and three mutation-free embryos and a subsequent pregnancy as measured by the rising hCG levels. Copyright © 2007 John Wiley & Sons, Ltd.
-
simultaneous Preimplantation Genetic Diagnosis for tay sachs and gaucher disease
2007Co-Authors: Gheona Altarescu, Ephrat Levylahad, Ehud J. Margalioth, Barry Brooks, Talia Eldar Geva, Paul RenbaumAbstract:Preimplantation Genetic Diagnosis (PGD) for single gene defects is described for a family in which each parent is a carrier of both Tay-Sachs (TS) and Gaucher disease (GD). A multiplex fluorescent polymerase chain reaction protocol was developed that simultaneously amplified all four familial mutations and 10 informative microsatellite markers. In one PGD cycle, seven blastomeres were analysed, reaching a conclusive Diagnosis in six out of seven embryos for TS and in five out of seven embryos for GD. Of the six diagnosed embryos, one was wild type for both TS and GD, and three were wild type for GD and carriers of TS. Two remaining embryos were compound heterozygotes for TS. Two transferable embryos developed into blastocysts (wt/wt and wt GD/carrier TS) and both were transferred on day 5. This single cycle of PGD resulted in a healthy live child. Allele drop-out (ADO) was observed in three of 34 reactions, yielding an 8% ADO rate. The occurrence of ADO in single cell analysis and undetected recombination events are primary causes of misDiagnosis in PGD and emphasize the need to use multiple polymorphic markers. So far as is known, this is the first report of concomitant PGD for two frequent Ashkenazi Jewish recessive disorders.