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Two professional societies recently published opinions on the clinical management of "mosaic" results from preimplantation genetic testing for aneuploidy (PGT-A) in human blastocyst-stage embryos in associations with in vitro fertilization (IVF). We here point out three principal shortcomings: (i) Though a most recent societal opinion states that it should not be understood as an endorsement of the use of PGT-A, any discussion of how PGT-A should be clinically interpreted for all practical purposes does offer such an endorsement. (ii) The same guideline derived much of its opinion from a preceding guidance in favor of utilization of PGT-A that did not follow even minimal professional requirements for establishment of practice guidelines. (iii) Published guidelines on so-called "mosaic" embryos from both societies contradict basic biological characteristics of human preimplantation-stage embryos. They, furthermore, are clinically unvalidated and interpret results of a test, increasingly seen as harmful to IVF outcomes for many infertile women. Qualified professional organizations, therefore, should finally offer transparent guidelines about the utilization of PGT-A in association with IVF in general. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate implantation potential of cleavage-stage embryos cultured in medium containing 2 ng/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) versus control medium, according to embryo morphological quality and then transferred on day 3.Methods: Explorative secondary data analysis of a multicenter, randomized, placebo-controlled, double-blinded prospective study of 1149 couples with embryo transfer after IVF/ICSI. This analysis includes a subgroup of 422 subjects with either single-embryo transfer (SET, N = 286) or double-embryo transfer of two embryos with equivalent morphological quality (DET, N = 136). Implantation rate and live birth rate were assessed according to category of morphological embryo quality on day 3.Results: Culture with GM-CSF did not increase the implantation rate for embryos classified as poor quality. A trend towards greater benefit of GM-CSF on implantation and survival until live birth for top-quality embryos (TQEs) compared with poor-quality embryos was observed, although not statistically significant. For TQEs, the percentage of transferred embryos resulting in a live born baby was: 40.9 ± 5.3% (GM-CSF) versus 30.5 ± 4.6% (control) (P = 0.24; odds ratio [OR] 1.43, 95% confidence interval [CI] 0.79-2.59), and for embryos with less than 6 cells at day 3 this same rate was: 7.4 ± 3.3% (GM-CSF) versus 12.0 ± 4.0% (control) (P = 0.26; OR 0.53, 95% CI 0.17-1.61).Conclusion: This exploratory analysis is consistent with GM-CSF protecting morphologically normal embryos from culture-induced stress and does not support an effect of GM-CSF in rescuing poor-quality embryos. ClinicalTrials.gov identifier: NCT00565747. [ABSTRACT FROM AUTHOR]

Objective: By focussing on differences in the mural granulosa cell (MGC) and cumulus cell (CC) transcriptomes from follicles resulting in competent (live birth) and non-competent (no pregnancy) oocytes the study aims on defining a competence classifier expression profile in the two cellular compartments. Design: A case-control study. Setting: University based facilities for clinical services and research. Patients: MGC and CC samples from 60 women undergoing IVF treatment following the long GnRH-agonist protocol were collected. Samples from 16 oocytes where live birth was achieved and 16 age- and embryo morphology matched incompetent oocytes were included in the study. Methods: MGC and CC were isolated immediately after oocyte retrieval. From the 16 competent and non-competent follicles, mRNA was extracted and expression profile generated on the Human Gene 1.0 ST Affymetrix array. Live birth prediction analysis using machine learning algorithms (support vector machines) with performance estimation by leave-one-out cross validation and independent validation on an external data set. Results: We defined a signature of 30 genes expressed in CC predictive of live birth. This live birth prediction model had an accuracy of 81%, a sensitivity of 0.83, a specificity of 0.80, a positive predictive value of 0.77, and a negative predictive value of 0.86. Receiver operating characteristic analysis found an area under the curve of 0.86, significantly greater than random chance. When applied on 3 external data sets with the end-point outcome measure of blastocyst formation, the signature resulted in 62%, 75% and 88% accuracy, respectively. The genes in the classifier are primarily connected to apoptosis and involvement in formation of extracellular matrix. We were not able to define a robust MGC classifier signature that could classify live birth with accuracy above random chance level. Conclusion: We have developed a cumulus cell classifier, which showed a promising performance on external data. This suggests that the gene signature at least partly include genes that relates to competence in the developing blastocyst. [ABSTRACT FROM AUTHOR]

BACKGROUND: There are limited data on the impact of different gonadotrophin preparations on embryo quality. [ABSTRACT FROM PUBLISHER]

Purpose: To use computer-controlled, multilevel embryo morphology analysis to quantify the reduction in cytoplasmic volume from the zygote stage to the combined volume of the individual blastomeres as an expression for the degree of fragmentation. Methods: Zygotes and their corresponding embryos from patients referred to ICSI treatment were analyzed. Sequences of digital images were taken focussing at 5-μm intervals through the zygotes and embryos. Assessment of cytoplasmic volumes and fragmentation were based on these sequences. Results: The mean cytoplasmic reduction of the embryos were significant linear increasing with increasing degree of fragmentation assessed by traditional evaluation (P < 0.001). Embryos scored to be highly fragmented had on average a cytoplasmic reduction of 63% larger than embryos assessed to have no fragmentation. In total, 68% of the embryos had a cytoplasmic reduction lying within their allocated fragmentation group. Conclusion: Assessment of embryonic fragmentation based on computer-controlled, multi-level embryo analysis of the blastomere volumes expressed in relation to the volume of the preceding zygote may allow a more precise and standardized evaluation of fragmentation than the traditional fragmentation assessment. [ABSTRACT FROM AUTHOR]

Objective: To study the relation between the resumption of mitosis after thaw and chromosomal constitution in frozen–thawed embryos. In addition, to evaluate the correlation among the three parameters of resumption of mitosis after thaw, postthaw blastomere loss, and multinucleation. Design: Frozen–thawed embryos were morphologically evaluated at thaw and after 24 hours of culture. Then, fluorescence in situ hybridization (FISH) analysis, including enumeration of 13 chromosomes, was performed by using a combination of peptide nucleic acid and DNA probes. Setting: In vitro fertilization laboratory. Patient(s): Forty IVF and/or intracytoplasmic sperm injection patients. Intervention(s): Embryo thawing, morphological evaluation, and fluorescence in situ hybridization analysis for aneuploidy screening. Main Outcome Measure(s): Resumption of mitosis, blastomere loss, multinucleation, and chromosome enumeration. Result(s): No difference was observed in the chromosomal constitution of embryos with and without resumption of mitosis. Neither was the postthaw blastomere loss connected to the chromosomal constitution. The resumption of mitosis was not associated with postthaw loss of blastomeres or with multinuclearity. Conclusion(s): Resumption of mitosis and blastomere loss of frozen–thawed embryos is not related to chromosome aberrations in the embryo. Further, the resumption of mitosis is not correlated with multinucleation. However, the high incidence of multinucleated embryos after thawing indicates that the freezing and thawing procedure may affect this condition. [Copyright &y& Elsevier]