Reprogenetics UK

Oxford, United Kingdom

Reprogenetics UK

Oxford, United Kingdom
SEARCH FILTERS
Time filter
Source Type

News Article | July 5, 2016
Site: www.techtimes.com

Ticked Off! Here's What You Need To Know About Lyme Disease A large study finds that combining two fertility tests could increase the success rate of in vitro fertilization (IVF). Researchers from the University of Oxford found that analyzing chromosomes for signs of problems as well as examining the mitochondrial DNA (mtDNA) can give couples a more accurate prognosis as to whether an IVF treatment will be successful. Apart from being the main energy providers to the embryo, mitochondria also have other critical roles to play. Past studies found that some embryos possess high levels of mtDNA, which prevent it from developing into a baby. In recent years, experts have been studying the mitochondria's crucial role in enabling women to produce healthy babies. In the new test, the combination involves the routine chromosomal screening and then analyzing further why the remaining embryos do not develop into a baby. The research team studied 280 embryos, which were grown in the laboratory for up to six days. They were deemed chromosomally normal. From the original batch, the researchers placed 111 embryos into women through IVF, and 78 of them (70 percent) resulted in ongoing pregnancies. The researchers noted that all successful pregnancies involved embryos with normal levels of mtDNA. Out of the 33 failed IVF, eight of them (24 percent) had remarkably high levels of mtDNA. "The results confirm that embryos with elevated levels of mitochondrial DNA rarely implant and support the use of mitochondrial quantification as a marker of embryo viability," said Dr. Epida Fragouli from the Reprogenetics UK as well as the Nuffield Department of Obstetrics and Gynaecology at the University of Oxford. The findings were presented at the European Society of Human Reproduction and Embryology conference held in Helsinki this week. The findings can lead to combined tests that can boost IVF success results in the United Kingdom. The same test is already being utilized in the United States. UK's Human Fertilisation and Embryology Authority is analyzing if the same test should be allowed within the UK. "It is looking promising and I think that we would certainly like to discuss it with our patients as an option for them," said consultant gynecologist Stuart Lavery, who is the IVF Hammersmith director at the Hammersmith hospital in London. According to the National Health Service, in 2010, the success rate of IVF treatments among women under 35 was 32.2 percent. For women aged 35 to 37, the success rate was 27.7 percent; for women aged 38 to 39, the success rate was 20.8 percent. For women aged 40 to 42, the IVF success rate was only 13.6 percent; women aged 43 and 44 had a success rate of 5 percent. Lastly, women aged over 44 had only 1.9 percent success rate. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


Munne S.,Reprogenetics | Held K.R.,Reprogenetics Germany | Magli C.M.,S.I.S.Me.R | Ata B.,Uludag University | And 5 more authors.
Fertility and Sterility | Year: 2012

Objective: To determine the extent of intra-age and intercycle variations in the frequency of first polar body aneuploidy in two consecutive cycles of oocyte retrieval undertaken by the same patient within 1 year. Design: Retrospective study. Setting: Fertility centers. Patient(s): Infertile couples undergoing IVF. Intervention(s): Patients underwent two consecutive cycles of preimplantation genetic screening through first polar body biopsy within 1 year. Main Outcome Measure(s): Meiosis I aneuploidy. Result(s): A total of 226 patients underwent 452 cycles of preimplantation genetic screening. Differences within age groups were wide, with 0-100% of oocytes being chromosomally normal in all age groups. Euploidy rates between centers were significantly different (48% vs. 25%). Intercycle differences for the same patient were also wide (0-100%), but with 68.5% of patients having less than ±2 euploid eggs of difference between cycles. Conclusion(s): Although euploidy rate decreased on average with advancing maternal age, the high intra-age and intercenter variation in oocyte chromosome abnormalities emphasize the difficulty in estimating how many euploid oocytes a specific woman will have. This may have repercussions for fertility preservation where a defined number of eggs are currently frozen just based on maternal age. © 2012 by American Society for Reproductive Medicine.


Fragouli E.,University of Oxford | Alfarawati S.,Reprogenetics UK | Spath K.,University of Oxford | Wells D.,University of Oxford
Molecular Human Reproduction | Year: 2014

Morphological assessments are the main way in which fertility clinics select in vitro generated embryo(s) for transfer to the uterus. However, it is widely acknowledged that the microscopic appearance of an embryo is only weakly correlated with its viability. Furthermore, the extent to which morphology is affected by aneuploidy, a genetic defectcommon in human preimplantation embryos, remains unclear. Aneuploidy is of great relevance to embryo selection as it represents one of the most important causes of implantation failure and miscarriage. The current studyaimed to examine whether morphological appearance can assist in identifying embryos at risk of aneuploidy. Additionally, the data produced sheds light on how chromosomal anomalies impact development from the cleavage to the blastocyst stage. A total of 1213 embryos were examined. Comprehensive chromosome analysis was combined with well-established criteria for the assessment of embryo morphology. At the cleavage stage, chromosome abnormalities were common even amongst embryos assigned the best morphological scores, indicating that aneuploidy has little effect on microscopic appearance at fixed time points up until Day 3 of development.However, at the blastocyst stage aneuploidies were found to be significantly lesscommonamong embryos of optimal morphological quality, while such abnormalities were overrepresented amongst embryos considered to be of poor morphology. Despite the link between aneuploidy and blastocyst appearance, many chromosomally abnormal embryos were able to achieve the highest morphological scores. In particular, blastocysts affected by forms of aneuploidy with the greatest capacity to produce clinical pregnancies (e.g. trisomy 21) were indistinguishable fromeuploid embryos. The sex ratiowas seen to be equal throughout preimplantation development. Interestingly, however, females were overrepresented amongst the fastest growing cleavage-stage embryos, whereas a sex-related skew in the opposite direction was noted for the most rapidly developing blastocysts. In summary, this study confirms that, at the cleavage stage, chromosome abnormalities have little if any effect on morphological scores assigned using traditional criteria. At the blastocyst stage some forms of aneuploidy begin to affect microscopic appearance, but in most instances the impact is subtle. In the case of the most clinically relevant aneuploidies (those capable of forming a pregnancy) there was no detectable effect on morphology at any preimplantation stage. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Fragouli E.,Reprogenetics UK | Spath K.,University of Oxford | Alfarawati S.,Reprogenetics UK | Kaper F.,Illumina | And 7 more authors.
PLoS Genetics | Year: 2015

Mitochondria play a vital role in embryo development. They are the principal site of energy production and have various other critical cellular functions. Despite the importance of this organelle, little is known about the extent of variation in mitochondrial DNA (mtDNA) between individual human embryos prior to implantation. This study investigated the biological and clinical relevance of the quantity of mtDNA in 379 embryos. These were examined via a combination of microarray comparative genomic hybridisation (aCGH), quantitative PCR and next generation sequencing (NGS), providing information on chromosomal status, amount of mtDNA, and presence of mutations in the mitochondrial genome. The quantity of mtDNA was significantly higher in embryos from older women (P=0.003). Additionally, mtDNA levels were elevated in aneuploid embryos, independent of age (P=0.025). Assessment of clinical outcomes after transfer of euploid embryos to the uterus revealed that blastocysts that successfully implanted tended to contain lower mtDNA quantities than those failing to implant (P=0.007). Importantly, an mtDNA quantity threshold was established, above which implantation was never observed. Subsequently, the predictive value of this threshold was confirmed in an independent blinded prospective study, indicating that abnormal mtDNA levels are present in 30% of non-implanting euploid embryos, but are not seen in embryos forming a viable pregnancy. NGS did not reveal any increase in mutation in blastocysts with elevated mtDNA levels. The results of this study suggest that increased mtDNA may be related to elevated metabolism and are associated with reduced viability, a possibility consistent with the ‘quiet embryo’ hypothesis. Importantly, the findings suggest a potential role for mitochondria in female reproductive aging and the genesis of aneuploidy. Of clinical significance, we propose that mtDNA content represents a novel biomarker with potential value for in vitro fertilisation (IVF) treatment, revealing chromosomally normal blastocysts incapable of producing a viable pregnancy. © 2015 Fragouli et al.


Munne S.,Reprogenetics | Fragouli E.,Reprogenetics UK | Colls P.,Reprogenetics | Katz-Jaffe M.G.,Colorado Center for Reproductive Medicine | And 3 more authors.
Reproductive BioMedicine Online | Year: 2010

Fluorescence in-situ hybridization (FISH) has been the principal method used for the identification and preferential transfer of chromosomally normal embryos, in the context of both preimplantation genetic diagnosis (PGD) and screening (PGS). Generally, the probe combinations used during PGS have focused on chromosomes frequently identified as abnormal in prenatal samples or material derived from first-trimester spontaneous abortions. Recent data, however, obtained with the use of comparative genomic hybridization (CGH), have suggested that commonly used PGS strategies may fail to detect a large number of aneuploidies affecting preimplantation embryos. Some chromosomes, which have been relatively neglected in PGS protocols thus far, display a disproportionate contribution to embryo aneuploidy and should be prioritized for screening. Using CGH data, it is possible to design new probe combinations that examine between 10 and 12 chromosomes and are capable of accurately diagnosing 89-91% of anomalies seen in embryos. At present, 24-chromosome tests, such as CGH, array CGH or single nucleotide polymorphism arrays, remain relatively costly and, in some cases, are yet to be fully validated. For these reasons, a cost-effective method, capable of accurately detecting almost all aneuploid embryos, represents an attractive alternative to comprehensive chromosome screening approaches. © 2009, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.


Fragouli E.,University of Oxford | Alfarawati S.,Reprogenetics UK | Spath K.,University of Oxford | Jaroudi S.,Reprogenetics UK | And 3 more authors.
Human Genetics | Year: 2013

Despite the clinical importance of aneuploidy, surprisingly little is known concerning its impact during the earliest stages of human development. This study aimed to shed light on the genesis, progression, and survival of different types of chromosome anomaly from the fertilized oocyte through the final stage of preimplantation development (blastocyst). 2,204 oocytes and embryos were examined using comprehensive cytogenetic methodology. A diverse array of chromosome abnormalities was detected, including many forms never recorded later in development. Advancing female age was associated with dramatic increase in aneuploidy rate and complex chromosomal abnormalities. Anaphase lag and congression failure were found to be important malsegregation causing mechanisms in oogenesis and during the first few mitotic divisions. All abnormalities appeared to be tolerated until activation of the embryonic genome, after which some forms started to decline in frequency. However, many aneuploidies continued to have little impact, with affected embryos successfully reaching the blastocyst stage. Results from the direct analyses of female meiotic divisions and early embryonic stages suggest that chromosome errors present during preimplantation development have origins that are more varied than those seen in later pregnancy, raising the intriguing possibility that the source of aneuploidy might modulate impact on embryo viability. The results of this study also narrow the window of time for selection against aneuploid embryos, indicating that most survive until the blastocyst stage and, since they are not detected in clinical pregnancies, must be lost around the time of implantation or shortly thereafter. © 2013 Springer-Verlag Berlin Heidelberg.


Fragouli E.,Reprogenetics UK | Wells D.,Reprogenetics UK | Wells D.,University of Oxford
Seminars in Reproductive Medicine | Year: 2012

Chromosome abnormalities are extremely common in human oocytes and embryos and are associated with a variety of negative outcomes for both natural cycles and those using assisted conception techniques. Embryos containing the wrong number of chromosomes (aneuploidy) may fail to implant in the uterus, miscarry, or lead to children with serious medical problems (e.g., Down syndrome). Preimplantation genetic screening (PGS) is a method that seeks to improve the outcomes of assisted reproductive treatments, such as in vitro fertilization (IVF), by ensuring that the embryos chosen for transfer to the uterus are chromosomally normal. Here we summarize published and novel data concerning the frequency and variety of chromosomal abnormalities seen in oocytes and embryos at the cleavage and blastocyst stages of development. Clinical outcomes of studies using PGS are presented, and the controversy over the use of chromosome screening as a tool for embryo selection is discussed. We describe validation and preliminary clinical data from the new generation of methods being used for PGS, including comparative genomic hybridization (CGH), microarrays (aCGH and single nucleotide polymorphism arrays), and quantitative polymerase chain reaction. These methodologies allow comprehensive chromosomal analysis, provide high accuracy, and have yielded encouraging preliminary clinical data. The combination of advances in genetics and embryology seems poised to usher in a new era in the treatment of infertility. Copyright © 2012 by Thieme Medical Publishers, Inc.


PubMed | Reprogenetics UK
Type: Journal Article | Journal: Seminars in reproductive medicine | Year: 2015

Mitochondria are the key regulators of multiple vital cellular processes, including apoptosis, calcium homeostasis, and the generation of ATP via the metabolic pathway known as oxidative phosphorylation. Unlike other cellular organelles, mitochondria contain one or more copies of their own genome (mtDNA). The mtDNA encodes a total of 13 genes with critical functions in cellular metabolism. The energy required to support the normal progress of preimplantation embryo development is provided in the form of ATP generated by the mitochondria. It has been suggested that cellular bioenergetic capacity and suboptimal levels of mitochondria-generated ATP could contribute to a variety of embryo developmental defects, and therefore adversely affect in vitro fertilization success rates. During this review, we discuss the role of mitochondria and their genome during oogenesis and early embryo development. We also assess whether analysis of mitochondria and their genome could be used as biomarkers to determine oocyte quality and embryo viability.


PubMed | Reprogenetics LLC, University of Oxford, Reprogenetics UK and Illumina
Type: Journal Article | Journal: PLoS genetics | Year: 2015

Mitochondria play a vital role in embryo development. They are the principal site of energy production and have various other critical cellular functions. Despite the importance of this organelle, little is known about the extent of variation in mitochondrial DNA (mtDNA) between individual human embryos prior to implantation. This study investigated the biological and clinical relevance of the quantity of mtDNA in 379 embryos. These were examined via a combination of microarray comparative genomic hybridisation (aCGH), quantitative PCR and next generation sequencing (NGS), providing information on chromosomal status, amount of mtDNA, and presence of mutations in the mitochondrial genome. The quantity of mtDNA was significantly higher in embryos from older women (P=0.003). Additionally, mtDNA levels were elevated in aneuploid embryos, independent of age (P=0.025). Assessment of clinical outcomes after transfer of euploid embryos to the uterus revealed that blastocysts that successfully implanted tended to contain lower mtDNA quantities than those failing to implant (P=0.007). Importantly, an mtDNA quantity threshold was established, above which implantation was never observed. Subsequently, the predictive value of this threshold was confirmed in an independent blinded prospective study, indicating that abnormal mtDNA levels are present in 30% of non-implanting euploid embryos, but are not seen in embryos forming a viable pregnancy. NGS did not reveal any increase in mutation in blastocysts with elevated mtDNA levels. The results of this study suggest that increased mtDNA may be related to elevated metabolism and are associated with reduced viability, a possibility consistent with the quiet embryo hypothesis. Importantly, the findings suggest a potential role for mitochondria in female reproductive aging and the genesis of aneuploidy. Of clinical significance, we propose that mtDNA content represents a novel biomarker with potential value for in vitro fertilisation (IVF) treatment, revealing chromosomally normal blastocysts incapable of producing a viable pregnancy.


PubMed | Reprogenetics UK
Type: Journal Article | Journal: Seminars in reproductive medicine | Year: 2012

Chromosome abnormalities are extremely common in human oocytes and embryos and are associated with a variety of negative outcomes for both natural cycles and those using assisted conception techniques. Embryos containing the wrong number of chromosomes (aneuploidy) may fail to implant in the uterus, miscarry, or lead to children with serious medical problems (e.g., Down syndrome). Preimplantation genetic screening (PGS) is a method that seeks to improve the outcomes of assisted reproductive treatments, such as in vitro fertilization (IVF), by ensuring that the embryos chosen for transfer to the uterus are chromosomally normal. Here we summarize published and novel data concerning the frequency and variety of chromosomal abnormalities seen in oocytes and embryos at the cleavage and blastocyst stages of development. Clinical outcomes of studies using PGS are presented, and the controversy over the use of chromosome screening as a tool for embryo selection is discussed. We describe validation and preliminary clinical data from the new generation of methods being used for PGS, including comparative genomic hybridization (CGH), microarrays (aCGH and single nucleotide polymorphism arrays), and quantitative polymerase chain reaction. These methodologies allow comprehensive chromosomal analysis, provide high accuracy, and have yielded encouraging preliminary clinical data. The combination of advances in genetics and embryology seems poised to usher in a new era in the treatment of infertility.

Loading Reprogenetics UK collaborators
Loading Reprogenetics UK collaborators