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Ottolini C.,Bridge Center | Ottolini C.,University of Kent | Rienzi L.,G.EN.E.R.A | Capalbo A.,G.EN.E.R.A
Reproductive BioMedicine Online | Year: 2014

Preimplantation genetic screening (PGS) for embryo aneuploidy using embryo biopsy is a widely available technique used to select embryos for transfer following IVF for certain patient populations. Since its introduction, there has been an ongoing search for a non-invasive technique to perform PGS. Such an advance would revolutionize the field of IVF enabling PGS to be used universally as a routine embryo selection tool with the potential to significantly increase pregnancy rates and decrease poor outcomes such as miscarriage. Recent publications illustrating the development of an algorithm using time-lapse imaging of IVF embryos have claimed to have done just this. We believe that the statements made in these articles, which include the proposed ability to increase pregnancy rates by determining embryo aneuploidy risk by time-lapse imaging, are premature and to this point unsubstantiated by the published data. We provide evidence from existing publications and from our own data that suggests that the statements recently made are misleading. We make the point that further investigation is needed either in the form of a larger, age-adjusted data set or preferably in a randomized controlled trial. © 2013, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. Source


Ottolini C.S.,Bridge Center | Ottolini C.S.,University of Kent | Newnham L.J.,University of Sussex | Capalbo A.,GENERA Gynecology | And 17 more authors.
Nature Genetics | Year: 2015

Crossover recombination reshuffles genes and prevents errors in segregation that lead to extra or missing chromosomes (aneuploidy) in human eggs, a major cause of pregnancy failure and congenital disorders. Here we generate genome-wide maps of crossovers and chromosome segregation patterns by recovering all three products of single female meioses. Genotyping >4 million informative SNPs from 23 complete meioses allowed us to map 2,032 maternal and 1,342 paternal crossovers and to infer the segregation patterns of 529 chromosome pairs. We uncover a new reverse chromosome segregation pattern in which both homologs separate their sister chromatids at meiosis I; detect selection for higher recombination rates in the female germ line by the elimination of aneuploid embryos; and report chromosomal drive against non-recombinant chromatids at meiosis II. Collectively, our findings show that recombination not only affects homolog segregation at meiosis I but also the fate of sister chromatids at meiosis II. © 2015 Nature America, Inc. All rights reserved. Source


Ferrero S.,Queen Mary, University of London | Ferrero S.,University of Genoa | Gillott D.J.,Queen Mary, University of London | Gillott D.J.,Bridge Center | And 2 more authors.
Journal of Endometriosis | Year: 2010

Objective: To determine the concentration of haptoglobin (Hp) in peritoneal fluid (PF) of women with and without endometriosis and its correlation with the phase of the menstrual cycle. The expression of Hpβe (determined by two-dimensional Polyacrylamide gel electrophoresis) was correlated to total PF Hp concentration. Materials and methods: PF samples were obtained from 240 women with or without endometriosis. PF Hp concentration was measured by a sandwich enzyme-linked immunosorbent assay. Hpβe expression in PF was estimated by two-dimensional polyacrylamide gel electrophoresis. Results: PF Hp concentration was similar in women with and without endometriosis; it was significantly higher during the luteal phase of the menstrual cycle than in the follicular phase in control subjects, but not in women with endometriosis. There was a positive correlation between serum progesterone level and PF Hp concentration in control subjects during the luteal phase of the menstrual cycle. There was a mild positive correlation between PF Hp concentration and Hpβe expression in controls but not in women with endometriosis. PF Hp concentration was not correlated with the ASRM stage of endometriosis and the type of endometriotic lesions. Conclusions: Women with and without endometriosis have similar PF Hp concentration. There is a mild positive correlation between PF Hp concentration and Hpβe expression in control subjects but not in women with endometriosis. Future investigations should aim to produce antibodies against specific epitopes of Hpβe that might allow its measurement by ELISA. © 2010 Wichtig Editore. Source


Levron J.,IVF Unit | Zinchenko V.,IVF Unit | Kol S.,IVF Unit | Direnfeld M.,Bridge Center | Bider D.,IVF Unit
Gynecological Endocrinology | Year: 2014

Two groups of egg recipients were treated, one in situ (165 patients; 195 cycles) and one after cross-border embryo transportation (340 cycles; 340 cycles) using mobile CO2 incubator. The positive pregnancy rate per cycle was 199/340 (58.6%) and 99/195 (50.7%) in the transportation and the traveling group, respectively (NS). The clinical pregnancy rate (fetal heart beat) was 48.1 and 43.1% per embryo transfer cycle, respectively (NS) and the delivery rate was 44.1 and 35.9% per embryo transfer cycle, respectively (p=0.01). Long distance transportation of human pre-implantation embryos using portable CO2 incubator is safe and do not jeopardize their developmental potential. © 2014 Informa UK Ltd. All rights reserved. Source


Natesan S.A.,Illumina | Bladon A.J.,Illumina | Coskun S.,King Faisal Specialist Hospital And Research Center | Qubbaj W.,King Faisal Specialist Hospital And Research Center | And 13 more authors.
Genetics in Medicine | Year: 2014

Purpose:Our aim was to compare the accuracy of family- or disease-specific targeted haplotyping and direct mutation-detection strategies with the accuracy of genome-wide mapping of the parental origin of each chromosome, or karyomapping, by single-nucleotide polymorphism genotyping of the parents, a close relative of known disease status, and the embryo cell(s) used for preimplantation genetic diagnosis of single-gene defects in a single cell or small numbers of cells biopsied from human embryos following in vitro fertilization.Methods:Genomic DNA and whole-genome amplification products from embryo samples, which were previously diagnosed by targeted haplotyping, were genotyped for single-nucleotide polymorphisms genome-wide detection and retrospectively analyzed blind by karyomapping.Results:Single-nucleotide polymorphism genotyping and karyomapping were successful in 213/218 (97.7%) samples from 44 preimplantation genetic diagnosis cycles for 25 single-gene defects with various modes of inheritance distributed widely across the genome. Karyomapping was concordant with targeted haplotyping in 208 (97.7%) samples, and the five nonconcordant samples were all in consanguineous regions with limited or inconsistent haplotyping results.Conclusion:Genome-wide karyomapping is highly accurate and facilitates analysis of the inheritance of almost any single-gene defect, or any combination of loci, at the single-cell level, greatly expanding the range of conditions for which preimplantation genetic diagnosis can be offered clinically without the need for customized test development.Genet Med 16 11, 838-845. Source

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