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Secreted miRNAs can be profiled with high accuracy and reproducibility from blastocyst spent culture media: a new potential biomarker for non-invasive embryo selection
No full textSecreted miRNAs can be profiled with high accuracy and reproducibility from blastocyst spent culture media: a new potential biomarker for non-invasive embryo selection
No full textDiscordant Growth of Monozygotic Twins Starts at the Blastocyst Stage: A Case Study
Full text linkSummaryDiscordant growth is a common complication of monochorionic/diamniotic pregnancies; in approximately 50% of cases, the cause is unknown. The case presented here suggests that discordant growth of monozygotic twins could start during preimplantation development. Two inner cell masses (ICMs) within the same blastocyst may originate in uneven splitting of a single “parental” ICM, or the two ICMs may be formed independently de novo. We studied the transcriptomes of two morphologically distinct ICMs within a single blastocyst using high-resolution RNA sequencing. The data indicated that the two ICM were at different stages of development; one was in the earliest stages of lineage commitment, while the other had already differentiated into epiblast and primitive endoderm. IGF1-mediated signaling is likely to play a key role in ICM growth and to be the major driver behind these differences
Increased risk of preterm birth and low birthweight with very high number of oocytes following IVF: an analysis of 65 868 singleton live birth outcomes
Full text linkIs there a relation between the number of oocytes retrieved following ovarian stimulation and obstetric outcomes of preterm birth (PTB) and low birthweight (LBW) following IVF treatment
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Definition and validation of a custom protocol to detect miRNAs in the spent media after blastocyst culture: searching for biomarkers of implantation
No full textSTUDY QUESTION: Can miRNAs be reliably detected in the spent blastocyst media (SBM) after IVF as putative biomarkers of the
implantation potential of euploid embryos?
SUMMARY ANSWER: Adjustment of the data for blastocyst quality and the day of full-expansion hinders the predictive power of a fast,
inexpensive, reproducible and user-friendly protocol based on the detection of 10 selected miRNAs from SBM.
WHAT IS KNOWN ALREADY: Euploidy represents so far the strongest predictor of blastocyst competence. Nevertheless, ∼50% of
the euploid blastocysts fail to implant. Several studies across the years have suggested that a dialogue exists between the embryo and the
endometrium aimed at the establishment of a pregnancy. MicroRNAs have been proposed as mediators of such a dialogue and investigated
in this respect. Several expensive, time-consuming and complex protocols have been adopted and promising results have been produced, but
conclusive evidence from large clinical studies is missing.
STUDY DESIGN, SIZE, DURATION: This study was conducted in two phases from September 2015 to December 2017. In Phase 1,
the human blastocyst miRNome profile was defined from the inner cell mass (ICM) and the corresponding whole-trophectoderm (TE) of six
donated blastocysts. Two different protocols were adopted to this end. In parallel, 6 pools of 10 SBM each were run (3 from only implanted
euploid blastocysts, IEBs; and 3 from only not-implanted euploid blastocysts, not-IEBs). A fast, inexpensive and user-friendly custom protocol
for miRNA SBM profiling was designed. In Phase 2, 239 SBM from IEB and not-IEB were collected at three IVF centres. After 18 SBM from
poor-quality blastocysts were excluded from the analysis, data from 107 SBM from not-IEB and 114 from IEB were produced through the
previously developed custom protocol and compared. The data were corrected through logistic regressions.
PARTICIPANT/MATERIALS, SETTINGS, METHODS: Donated blastocysts underwent ICM and whole-TE isolation. SBM were
collected during IVF cycles characterized by ICSI, blastocyst culture in a continuous media, TE biopsy without zona pellucida opening in
Day 3, quantitative PCR (qPCR)-based aneuploidy testing and vitrified-warmed single euploid embryo transfer. Not-IEB and IEB were clustered
following a negative pregnancy test and a live birth, respectively. The Taqman Low Density Array (TLDA) cards and the Exiqon microRNA
human panel I+II qPCR analysis protocols were adopted to analyse the ICM and whole-TE. The latter was used also for SBM pools. A custom
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Customized miRNA analysis in spent IVF media 1747
protocol and plate was then designed based on the Exiqon workflow, validated and finally adopted for SBM analysis in study Phase 2. This
custom protocol allows the analysis of 10 miRNAs from 10 SBM in 3 hours from sample collection to data inspection.
MAIN RESULTS AND ROLE OF THE CHANCE: The TLDA cards protocol involved a higher rate of false positive results (5.6% versus
2.8% with Exiqon). There were 44 miRNAs detected in the ICM and TE from both the protocols. One and 24 miRNAs were instead detected
solely in the ICM and the TE, respectively. Overall, 29 miRNAs were detected in the pooled SBM: 8 only from not-IEB, 8 only from IEB and 13
from both. Most of them (N = 24/29, 82.7%) were also detected previously in both the ICM and TE with the Exiqon protocol; two miRNAs
(N = 2/29, 6.9%) were previously detected only in the TE, and three (N = 3/29, 10.3%) were never detected previously. In study Phase 2,
significant differences were shown between not-IEB and IEB in terms of both miRNA detection and relative quantitation. However, when the
data were corrected for embryo morphology and day of full development (i.e. SBM collection), no significant association was confirmed.
LIMITATIONS, REASONS FOR CAUTION: This study did not evaluate specifically exosomal miRNAs, thereby reducing the chance of
identifying the functional miRNAs. Ex-vivo experiments are required to confirm the role of miRNAs in mediating the dialogue with endometrial
cells, and higher throughput technologies need to be further evaluated for miRNA profiling from clinical SBM samples.
WIDER IMPLICATIONS OF THE FINDINGS: Although no clinical predictive power was reported in this study, the absence of invasiveness
related with SBM analysis and the evidence that embryonic genetic material can be reliably detected and analysed from SBM make this waste
product of IVF an important source for further investigations aimed at improving embryo selection.
STUDY FUNDING/COMPETING INTEREST(S): This project has been financially supported by Merck KgaA (Darmstadt, Germany)
with a Grant for Fertility Innovation (GFI) 2015. The authors have no conflict of interest to declare related with this stud
Human Embryos Created by Embryo Splitting Secrete Significantly Lower Levels of miRNA-30c
Full text linkStudies reporting term pregnancy and the production of genetically identical offspring from isolated blastomeres of early stage embryos have been carried out in small and large animals. However, very little is known about the effects of embryo splitting on the development and reproductive competency of human embryos. Here, we investigated the effects of embryo splitting on profile of miRNAs detected in their spent blastocyst medium (SBM) by comparative analysis of miRNA profiles in SBM of human twin embryos created by blastomere biopsy and SBM of blastocysts that resulted in a healthy pregnancy and live birth following embryo transfer. The profile of miRNA secretion in in vitro culture media consistently distinguishes twin from control embryos. We found that six miRNAs are significantly more abundant in SBM from twin embryos, while nine are significantly more abundant in SBM from euploid implanted blastocysts. These nine include miRNA-30c, a previously reported marker of blastocyst implantation potential. Furthermore, 22.9% of miRNAs secreted by twin embryos were never detected in SBM from normal, reproductively competent blastocysts, or from TE samples from normal blastocysts donated for the research. The miRNA profile, unique to twin blastocysts, might be a result of differential lineage commitment in these embryos
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