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Dive into the research topics where A. Mantzouratou is active.

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Featured researches published by A. Mantzouratou.


Cytogenetic and Genome Research | 2011

ANEUPLOIDY IN THE HUMAN CLEAVAGE STAGE EMBRYO

A. Mantzouratou; Joy D. A. Delhanty

The cleavage stage embryo (days 1–3) stands out due to the high level of chromosomal anomalies, especially mosaicism that arises prior to global embryonic genome activation. Molecular cytogenetic studies show that an average of 60% of in vitro derived embryos have at least one aneuploid cell by the time they are 3 days old. However, comprehensive studies of the chromosome content of individual cells have revealed that 25% of these embryos have no aneuploid cells, a fact that sits well with the knowledge that at most 1 in 5 have the capacity to implant. The evidence is that extensive mosaicism, affecting several chromosomes, interferes with development to a greater extent than does uniform aneuploidy. Follow-up studies on embryos after pre-implantation genetic aneuploidy screening indicate that the frequency of meiotic errors varies according to the referral reason, with the highest frequency being recorded for the recurrent miscarriage category and the lowest in the repeated implantation failure group where younger women have a good response to ovarian stimulation. The exceptionally high incidence of pre- and post-zygotic chromosomal anomalies seen in early human embryos is thus the product of several mechanisms. Firstly, the error-prone cell cycle during the embryonic cleavage stage and secondly, parental susceptibility to meiotic and mitotic chromosomal instability together with their general genetic background.


Reproductive Biomedicine Online | 2011

The nature and origin of binucleate cells in human preimplantation embryos: relevance to placental mesenchymal dysplasia

L. Xanthopoulou; Joy D. A. Delhanty; Anastasia Mania; T Mamas; Paul Serhal; Sioban SenGupta; A. Mantzouratou

Cleavage-stage embryos often have nuclear abnormalities, one of the most common being binucleate blastomeres, which may contain two diploid or two haploid nuclei. Biopsied cells from preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) cycles were studied to determine the relative frequency of binucleate cells with two haploid versus two diploid nuclei. The frequency of mononucleate haploid biopsied blastomeres was also recorded. In the chromosomal PGD cycles 45.2% of the biopsied binucleate cells were overall diploid and 38.7% were overall tetraploid, compared with 50.0% and 29.2% for the PGS group, respectively. Placental mesenchymal dysplasia is a rare condition associated with intrauterine growth restriction, prematurity and intrauterine death. Recent work suggests that androgenetic diploid/haploid mosaicism may be a causal mechanism. There are two possible origins of haploid nuclei, either the cell contained only one parental genome initially or they may be derived from the cytokinesis of binucleate cells with two haploid nuclei. Binucleate formation therefore may be a way of doubling up the haploid genome, to produce diploid cells of androgenetic origin as seen in placental mesenchymal dysplasia.


Cytogenetic and Genome Research | 2012

Chromosome Breakage in Human Preimplantation Embryos from Carriers of Structural Chromosomal Abnormalities in Relation to Fragile Sites, Maternal Age, and Poor Sperm Factors

L. Xanthopoulou; Harita Ghevaria; A. Mantzouratou; Paul Serhal; Alpesh Doshi; Joy D. A. Delhanty

Chromosome breakage is a fairly widespread phenomenon in preimplantation embryos affecting at least 10% of day 3 cleavage stage embryos. It may be detected during preimplantation genetic diagnosis (PGD). For carriers of structural chromosomal abnormalities, PGD involves the removal and testing of single blastomeres from cleavage stage embryos, aiming towards an unaffected pregnancy. Twenty-two such couples were referred for PGD, and biopsied blastomeres on day 3 and untransferred embryos (day 5/6) were tested using fluorescence in situ hybridisation (FISH) with appropriate probes. This study investigated whether chromosome breakage (a) was detected more frequently in cases where the breakpoint of the aberration was in the same chromosomal band as a fragile site and (b) was influenced by maternal age, sperm parameters, reproductive history, or the sex of the carrier parent. The frequency of breakage seemed to be independent of fragile sites, maternal age, reproductive history, and sex of the carrier parent. However, chromosome breakage was very significantly higher in embryos from male carriers with poor sperm parameters versus embryos from male carriers with normal sperm parameters. Consequently, embryos from certain couples were more prone to chromosome breakage, fragment loss, and hence chromosomally unbalanced embryos, independently of meiotic segregation.


Molecular Cytogenetics | 2009

Meiotic and mitotic behaviour of a ring/deleted chromosome 22 in human embryos determined by preimplantation genetic diagnosis for a maternal carrier

A. Mantzouratou; Anastasia Mania; Marianna Apergi; Sarah Laver; Paul Serhal; Joy D. A. Delhanty

BackgroundRing chromosomes are normally associated with developmental anomalies and are rarely inherited. An exception to this rule is provided by deletion/ring cases. We were provided with a unique opportunity to investigate the meiotic segregation at oogenesis in a woman who is a carrier of a deleted/ring 22 chromosome. The couple requested preimplantation genetic diagnosis (PGD) following the birth of a son with a mosaic karyotype.The couple underwent two cycles of PGD. Studies were performed on lymphocytes, single embryonic cells removed from 3 day-old embryos and un-transferred embryos. Analysis was carried out using fluorescence in situ hybridisation (FISH) with specific probe sets in two rounds of hybridization.ResultsIn total, 12 embryos were biopsied, and follow up information was obtained for 10 embryos. No embryos were completely normal or balanced for chromosome 22 by day 5. There was only one embryo diagnosed as balanced of 12 biopsied but that accumulated postzygotic errors by day 5. Three oocytes apparently had a balanced chromosome 22 complement but all had the deleted and the ring 22 and not the intact chromosome 22. After fertilisation all the embryos accumulated postzygotic errors for chromosome 22.ConclusionThe study of the preimplantation embryos in this case provided a rare and significant chance to study and understand the phenomena associated with this unusual type of anomaly during meiosis and in the earliest stages of development. It is the first reported PGD attempt for a ring chromosome abnormality.


Reproductive Biomedicine Online | 2014

Telomere length in human blastocysts.

Anastasia Mania; A. Mantzouratou; Joy D. A. Delhanty; Gianluca Baio; Paul Serhal; Sioban SenGupta

This is a retrospective study aiming to assess telomere length in human embryos 4 days post fertilization and to determine whether it is correlated to chromosomal ploidy, embryo developmental rate and patient age. Embryos were donated from patients undergoing treatment in the assisted conception unit. Seven couples took part, generating 35 embryos consisting of 1130 cells. Quantitative fluorescent in-situ hybridization (FISH) measured the telomere length of every cell using a pan-telomeric probe. Conventional FISH on six chromosomes was used to assess aneuploidy in the same cells. Maternal and paternal age, referral reason, embryo developmental rate and type of chromosomal error were taken into account. Chromosomally abnormal cells were associated with shorter telomeres than normal cells for embryos that were developmentally slow. Cells produced by women of advanced maternal age and those with a history of repeated miscarriage tended to have substantially shorter telomeres. There was no significant difference in telomere length with respect to the rate of embryo development 5 days post fertilization. Telomeres play an important role in cell division and shorter telomeres may affect embryonic ploidy. Reduced telomere length was associated with aneuploid cells and embryos from women of advanced maternal age.


Prenatal Diagnosis | 2011

When is old too old for preimplantation genetic diagnosis for reciprocal translocations

L. Xanthopoulou; A. Mantzouratou; Anastasia Mania; H. Ghevaria; C. Ghebo; Paul Serhal; Joy D. A. Delhanty

Preimplantation genetic diagnosis (PGD) was developed as an alternative to prenatal diagnosis and involves the removal and testing of one or two blastomeres from in vitro fertilisation (IVF) generated embryos to select those embryos that are unaffected by a single gene or a chromosomal abnormality (Fragouli, 2007). Couples who are at risk of having a child with a specific single gene or chromosomal abnormality may opt to have PGD to avoid an affected pregnancy and to avoid having prenatal diagnosis that is associated with a 1% risk of miscarriage; moreover, their decision to have PGD is often linked to the couple’s view on pregnancy termination. At the same time, other couples who seek PGD have difficulty in achieving a pregnancy because of infertility or subfertility or are victims of repeated pregnancy loss. Fluorescence in situ hybridization (FISH) is used in PGD for the investigation of numerical and structural chromosomal abnormalities. It involves using a fluorescently labelled DNA probe, which will bind to its complementary sequence in the genome and as a result detect a chromosome or a part of a chromosome, thereby allowing determination of the copy number of that region in a particular sample (Hopman et al., 1988). Reciprocal translocations are the most common type of structural chromosomal abnormality in humans, seen in about 1 in 500 live births (Jacobs et al., 1992) and involve the exchange of genetic material between different chromosomes. Carriers are usually phenotypically normal because there is no loss of genetic material but are faced with unfavourable meiotic segregation when the translocation chromosomes pair up at meiosis. Therefore, carriers are at a high risk of producing unbalanced gametes and hence, genetically abnormal embryos are associated with recurrent miscarriage, infertility and abnormal offspring.


Molecular Cytogenetics | 2010

Male and female meiotic behaviour of an intrachromosomal insertion determined by preimplantation genetic diagnosis

L. Xanthopoulou; A. Mantzouratou; Anastasia Mania; Suzanne Cawood; Alpesh Doshi; Domenico M. Ranieri; Joy D. A. Delhanty

BackgroundTwo related family members, a female and a male balanced carrier of an intrachromosomal insertion on chromosome 7 were referred to our centre for preimplantation genetic diagnosis. This presented a rare opportunity to investigate the behaviour of the insertion chromosome during meiosis in two related carriers. The aim of this study was to carry out a detailed genetic analysis of the preimplantation embryos that were generated from the three treatment cycles for the male and two for the female carrier.Patients underwent in vitro fertilization and on day 3, 22 embryos from the female carrier and 19 embryos from the male carrier were biopsied and cells analysed by fluorescent in situ hybridization. Follow up analysis of 29 untransferred embryos was also performed for confirmation of the diagnosis and to obtain information on meiotic and mitotic outcome.ResultsIn this study, the female carrier produced more than twice as many chromosomally balanced embryos as the male (76.5% vs. 36%), and two pregnancies were achieved for her. Follow up analysis showed that the male carrier had produced more highly abnormal embryos than the female (25% and 15% respectively) and no pregnancies occurred for the male carrier and his partner.ConclusionThis study compares how an intrachromosomal insertion has behaved in the meiotic and preimplantation stages of development in sibling male and female carriers. It confirms that PGD is an appropriate treatment in such cases. Reasons for the differing outcome for the two carriers are discussed.


Reproductive Biomedicine Online | 2010

P2 Sex chromosome abnormalities in embryos from women undergoing PGS: Focus on meiotic errors involving the X-chromosome

Harita Ghevaria; A. Mantzouratou; L. Xanthopoulou; Paul Serhal; Joyce C. Harper; Joy D. A. Delhanty

P1 Preimplantation genetic diagnosis and maternal age: the effect of embryo cohort size N. Ercelen1, E. Tutar1, M. Gultomruk1, H. Comert1, B. Yazar1, B. Balaban2, B. Urman2. 1American Hospital Genetic Disease Diagnostics Center, Guzelbahce Sok. No: 20, 34365 Nisantasi, Istanbul, Turkey, 2American Hospital Ob-Gyn and Reproductive Medicine Unit, Guzelbahce Sok. No: 20, 34365 Nisantasi, Istanbul, Turkey


Human Reproduction | 2007

Variable aneuploidy mechanisms in embryos from couples with poor reproductive histories undergoing preimplantation genetic screening

A. Mantzouratou; Anastasia Mania; Elpida Fragouli; L. Xanthopoulou; S Tashkandi; Karen Fordham; Domenico Massimo Ranieri; Alpesh Doshi; S Nuttall; Joyce C. Harper; Paul Serhal; Joy D. A. Delhanty


Prenatal Diagnosis | 2003

Preimplantation genetic diagnosis of chromosome abnormalities: Implications from the outcome for couples with chromosomal rearrangements

M. Simopoulou; Joyce C. Harper; Elpida Fragouli; A. Mantzouratou; B. E. Speyer; Paul Serhal; D. M. Ranieri; Alpesh Doshi; J. Henderson; Charles H. Rodeck; Joy D. A. Delhanty

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L. Xanthopoulou

University College London

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Paul Serhal

University College Hospital

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Anastasia Mania

University College London

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Joyce C. Harper

University College London

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Alpesh Doshi

University College Hospital

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S Tashkandi

University College London

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Sioban SenGupta

University College London

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