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| ==Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage==
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| Nat Biotechnol. 2010 Oct 3. [Epub ahead of print]
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| Wong CC, Loewke KE, Bossert NL, Behr B, De Jonge CJ, Baer TM, Pera RA.
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| [1] Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, California, USA. [2] Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, California, USA. [3] These authors contributed equally to this work.
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| Abstract
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| We report studies of preimplantation human embryo development that correlate time-lapse image analysis and gene expression profiling. By examining a large set of zygotes from in vitro fertilization (IVF), we find that success in progression to the blastocyst stage can be predicted with >93% sensitivity and specificity by measuring three dynamic, noninvasive imaging parameters by day 2 after fertilization, before embryonic genome activation (EGA). These parameters can be reliably monitored by automated image analysis, confirming that successful development follows a set of carefully orchestrated and predictable events. Moreover, we show that imaging phenotypes reflect molecular programs of the embryo and of individual blastomeres. Single-cell gene expression analysis reveals that blastomeres develop cell autonomously, with some cells advancing to EGA and others arresting. These studies indicate that success and failure in human embryo development is largely determined before EGA. Our methods and algorithms may provide an approach for early diagnosis of embryo potential in assisted reproduction.
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| PMID: 20890283
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| http://www.ncbi.nlm.nih.gov/pubmed/20890283?dopt=Abstract
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| http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.1686.html
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| ==Timeline==
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| * 1959 Min Chueh Chang, working in the United States, had managed to carry out IVF in rabbits.
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| * 1960s, and now based at Cambridge University, that he read of Patrick Steptoe’s experience in using the then novel technique of laparoscopy.
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| (The first 100 or so attempts ended in failure, with the embryo dying early on in the pregnancy.)
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| http://www.bmj.com/content/341/bmj.c5533.full
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| ==Other Species==
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| * Sheep (ovine) http://www.ncbi.nlm.nih.gov/pubmed/20615540
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| * Horse (equine) http://www.ncbi.nlm.nih.gov/pubmed/20591059
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| SMH 2004 article - http://www.smh.com.au/articles/2004/09/13/1094927508626.html
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| ===Preimplantation mouse embryo selection guided by light-induced dielectrophoresis===
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| PLoS One. 2010 Apr 13;5(4):e10160.
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| Valley JK, Swinton P, Boscardin WJ, Lue TF, Rinaudo PF, Wu MC, Garcia MM.
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| Berkeley Sensor & Actuator Center, Electrical Engineering and Computer Sciences, University of California, Berkeley, California, United States of America.
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| Abstract
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| Selection of optimal quality embryos for in vitro fertilization (IVF) transfer is critical to successful live birth outcomes. Currently, embryos are chosen based on subjective assessment of morphologic developmental maturity. A non-invasive means to quantitatively measure an embryo's developmental maturity would reduce the variability introduced by the current standard. We present a method that exploits the scaling electrical properties of pre-transfer embryos to quantitatively discern embryo developmental maturity using light-induced dielectrophoresis (DEP). We show that an embryo's DEP response is highly correlated with its developmental stage. Uniquely, this technique allows one to select, in sequence and under blinded conditions, the most developmentally mature embryos among a mixed cohort of morphologically indistinguishable embryos cultured in optimized and sub-optimal culture media. Following assay, embryos continue to develop normally in vitro. Light-induced dielectrophoresis provides a non-invasive, quantitative, and reproducible means to select embryos for applications including IVF transfer and embryonic stem cell harvest.
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| PMID: 20405021
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| http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010160
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| ===Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome?===
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| Fertil Steril. 2010 Oct;94(5):1680-3. Epub 2010 Feb 4.
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| Källén B, Finnström O, Lindam A, Nilsson E, Nygren KG, Olausson PO.
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| Tornblad Institute, University of Lund, Lund, Sweden. Bengt.Kallen@med.lu.se
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| Abstract
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| OBJECTIVE: To compare neonatal outcome of blastocyst and cleavage stage embryo transfers after IVF.
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| DESIGN: Register study.
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| SETTING: Births recorded in the Swedish Medical Birth Register after IVF performed, 2002-2006.
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| PATIENT(S): Treatments reported from all Swedish IVF clinics.
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| INTERVENTION(S): None.
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| MAIN OUTCOME MEASURE(S): Some neonatal characteristics were compared in 1,311 infants born after blastocyst-stage transfer and 12,562 infants born after cleavage-stage transfer. Comparisons were also made with all births, 2002-2007 (n = 598,687).
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| RESULT(S): After adjusting for year of birth, maternal age, parity, smoking habits, and body mass index, the risk of preterm birth among singletons was significantly greater after blastocyst-stage transfer than after cleavage-stage transfer. The risk of congenital malformations was also significantly higher. When the analysis was restricted to clinics where blastocyst transfers were made, the risk estimates increased for preterm birth, low birth weight, low APGAR score, and respiratory diagnoses, but did not change for congenital malformations.
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| CONCLUSION(S): The results indicate a small increase in risk associated with blastocyst transfer, perhaps owing to the longer period of in vitro culture. There is a possibility that this effect is due, at least in part, to a selection of women for blastocyst transfers. Further studies are needed either to verify or to refute the found associations.
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| PMID: 20137785
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| ===Comparison of the major malformation rate of children conceived from cryopreserved embryos and fresh embryos===
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| Chin Med J (Engl). 2010 Jul;123(14):1893-7.
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| Li HZ, Qiao J, Chi HB, Chen XN, Liu P, Ma CH.
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| Medical Center for Human Reproduction, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
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| Abstract
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| BACKGROUND: Cryopreserved embryo transfer has become indispensable in reproductive technology. More and more children are conceived from frozen-thawed embryo transfer (FET). The risk of birth defects associated with frozen-thawed embryo transfer has been evaluated and conflict results are obtained. The aim of this study was to compare the rate of major malformations in children conceived from cryopreserved embryos with that of children from fresh embryos.
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| METHODS: A retrospective analysis was performed on children conceived from frozen-thawed embryos and fresh embryos between January 2005 and December 2008 at the Reproduction Center of the Third Hospital, Peking University. The major malformation rates were compared between two groups for all children, as well as singletons or twins, separately. The frequencies of different subtypes of malformations classified according to different organ system were also compared.
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| RESULTS: Thirty-four of 3125 children from cryopreserved embryos had a major malformation. The malformation rate was 1.09%, which was comparable to that for children after fresh embryos transfer (1.53% (55/3604), OR: 0.71, 95%CI; 0.46-1.09). The malformation rate was also similar when the analysis was limited to children from cryopreserved embryos resulted from in vitro fertilization (IVF) (1.39%) and fresh IVF (1.3%). However, children from cryopreserved embryos resulted from intracytoplasmic sperm injections (ICSI) had much lower malformation rate than from fresh ICSI (0.63% vs.1.83%, OR: 0.34, 95%CI: 0.16-0.75). No difference was found in the incidence of major malformations in singletons from cryo ICSI (0.73%) and fresh ICSI (1.9%), or from cryo IVF (1.49%) and fresh IVF (1.67%). Similar malformation rate was found in multiples from cryo ICSI (0.52%) and fresh ICSI (1.76%), or cryo IVF (1.30%) and fresh IVF (0.90%). The distribution and risk of the subtype of malformations, such as cardiovascular, gastrointestinal, neural tube, urogenital, musculoskeletal and facial abnormalities was not different between the cryo group and fresh group.
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| CONCLUSIONS: The major malformation rate is similar between fetuses/children conceived from cryopreserved embryos and those from fresh embryos. Large prospective and long-term follow-up studies are needed to get exact results concerning the birth defects of the children born after cryopreserved embryos.
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| PMID: 20819574
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| http://www.ncbi.nlm.nih.gov/pubmed/20819574
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| ==Trends in delivery and neonatal outcome after in vitro fertilization in Sweden: data for 25 years.==
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| Hum Reprod. 2010 Apr;25(4):1026-34. Epub 2010 Feb 5.
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| Källén B, Finnström O, Lindam A, Nilsson E, Nygren KG, Otterblad Olausson P.
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| Tornblad Institute, University of Lund, Biskopsgatan 7, SE-223 62 Lund, Sweden. bengt.kallen@med.lu.se
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| Abstract
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| BACKGROUND: Marked changes have occurred in in vitro fertilization (IVF) methodology during the past 25 years but also in characteristics of couples undergoing treatment.
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| METHODS: This study was based on 27 386 women undergoing IVF treatment from 1982 to 2006 and giving birth to 31 850 infants. Outcomes of deliveries were studied using Swedish health registers. Comparisons were made with all deliveries in the population (n = 2 603 601). Adjusted odds ratios were calculated when important changes in background rates had occurred.
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| RESULTS: There was a substantial increase in the use of intracytoplasmatic sperm injection (ICSI) and the transfer of cryopreserved embryos. Among all ICSI cases, the proportion using epididymal or testicular sperm varied between 5 and 10%. Maternal characteristics changed during the observation period but the median age remained relatively constant in spite of the increasing maternal age in the population. There was a decline in the rate of some maternal pregnancy diagnoses (notably pre-eclampsia, premature rupture of membranes) and some neonatal diagnoses (notably preterm births, low birthweight, cerebral hemorrhage, respiratory diagnoses, use of continuous positive airway pressure and mechanical ventilation, sepsis/pneumonia). Up till 1992, the twinning rate increased to a maximum of about 30% and then declined to 5% towards the end of the period whereas higher order multiples nearly disappeared. The total rate of infants with congenital malformations changed only little.
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| CONCLUSIONS: The decrease in unwanted outcomes can, to a large extent, be explained by the reduced rate of multiple births but was seen also among singletons. Other explanations can be sought in changes in the characteristics of patients undergoing IVF.
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| PMID: 20139431 [PubMed - indexed for MEDLINE]
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| ==Effects==
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| * Effects of In Vitro Maturation on Histone Acetylation in Metaphase II Oocytes and Early Cleavage Embryos. http://www.ncbi.nlm.nih.gov/pubmed/20613962
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| ** free article http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896857/?tool=pubmed
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| * Reorganization of the Endoplasmic Reticulum and Development of Ca2+ Release Mechanisms During Meiotic Maturation of Human Oocytes. http://www.ncbi.nlm.nih.gov/pubmed/20610804
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| ** "Oocyte maturation in rodents is characterized by a dramatic reorganization of the endoplasmic reticulum (ER) and an increase in the ability of an oocyte to release Ca(2+) in response to fertilization or inositol 1,4,5-trisphosphate (IP(3)). We examined if human oocytes undergo similar changes during cytoplasmic meiotic maturation both in vivo and in vitro. Immature, germinal vesicle (GV)-stage oocytes had a fine network of ER throughout the cortex and interior, whereas the ER in in vivo-matured metaphase II (MII)-stage oocytes was organized in large (~2-3 microm) accumulations throughout the cortex and interior. Likewise, oocytes matured in vitro exhibited cortical and interior clusters with no apparent polarity with regard to the meiotic spindle. In vivo-matured oocytes contained approximately 1.5X the amount of IP3 receptor protein and released significantly more Ca(2+) in response to IP(3) than GV-stage oocytes; however, oocytes matured in vitro did not contain more IP(3) receptor protein or release more Ca(2+) in response to IP(3) than GV-stage oocytes. These results show that at least one cytoplasmic change occurs during in vitro maturation of human oocytes that might be important for fertilization and subsequent embryonic development but suggest that a low developmental competence of in vitro matured oocytes could be due to deficiencies in the ability to release Ca(2+) at fertilization."
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