Safer embryo tests could boost IVF pregnancy rates

Pearson, Helen

doi:10.1038/444012b

Cited by 8 publications

(6 citation statements)

References 4 publications

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“…There is a need to identify viable embryos with the highest implantation potential to increase IVF success rates, reduce the number of embryos for fresh replacement, lower multiple pregnancy rates and lower early pregnancy losses. For all these reasons, several biomarkers for embryo selection are currently being investigated (Pearson, 2006;Haouzi et al, 2008). As embryos that result in pregnancy differ in their metabolomic profiles compared with embryos that do not, some studies are trying to identify a molecular signature that can be detected by non-invasive evaluation of the embryo culture medium (Gardner et al, 2001;Brison et al, 2004;Sakkas and Gardner, 2005;Seli et al, 2007;Zhu et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

A non-invasive test for assessing embryo potential by gene expression profiles of human cumulus cells: a proof of concept study

Assou

Haouzi

Mahmoud³

et al. 2008

Molecular Human Reproduction

192

130

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Identification of new criteria for embryo quality is required to improve the clinical outcome of in vitro fertilization. The aim of this study was to determine the gene expression profile of cumulus cells (CC) surrounding the oocyte as biomarkers for embryo potential and to identify genes to be used as prognostic indicators of successful pregnancy. CC from single oocytes were analysed using DNA microarrays. Gene expression profiles of CC surrounding the oocyte associated with good embryonic quality and pregnancy outcome were computed. We observed that CC issued from oocytes that developed into embryos with a good morphology had differing gene expression profile according to the pregnancy outcome of the embryo. We demonstrated that the expression of BCL2L11, PCK1 and NFIB in CC is significantly correlated with embryo potential and successful pregnancy. These results were confirmed by quantitative RT-PCR. The gene expression profiling of human CC correlates with embryo potential and pregnancy outcome. BCL2L11, PCK1 and NFIB genes are proposed as biomarkers for predicting pregnancy. Our findings suggest a non-invasive approach, offering a new potential strategy for competent embryo selection. This approach should be validated in single-embryo transfer programmes.

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Section: Introductionmentioning

confidence: 99%

A non-invasive test for assessing embryo potential by gene expression profiles of human cumulus cells: a proof of concept study

Assou

Haouzi

Mahmoud³

et al. 2008

Molecular Human Reproduction

192

130

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“…As the developmental potential of an embryo cannot be fully determined by characteristics visible by microscopy alone, several other markers are studied (Pearson, 2006). For instance, several investigators focused on the influence of the follicular micro-environment on subsequent embryonic development.…”

Section: Introductionmentioning

confidence: 99%

Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis

Montfoort

Geraedts

Dumoulin

et al. 2008

Molecular Human Reproduction

156

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Besides the established selection criteria based on embryo morphology and blastomere number, new parameters for embryo viability are needed to improve the clinical outcome of IVF and more particular of elective single-embryo transfer. Genome-wide gene expression in cumulus cells was studied, since these cells surround the oocyte inside the follicle and therefore possibly reflect oocyte developmental potential. Early cleavage (EC) was chosen as a parameter for embryo viability. Gene expression in cumulus cells from eight oocytes resulting in an EC embryo (EC-CC; n = 8) and from eight oocytes resulting in a non-EC (NEC) embryo (NEC-CC; n = 8) was analysed using microarrays (n = 16). A total of 611 genes were differentially expressed (P < 0.01), mainly involved in cell cycle, angiogenesis, apoptosis, epidermal growth factor, fibroblast growth factor and platelet-derived growth factor signalling, general vesicle transport and chemokine and cytokine signalling. Of the 25 selected differentially expressed genes analysed by quantitative real-time PCR 15 (60%) genes could be validated in the original samples. Of these 8 (53%) could also be validated in 24 (12-EC-CC and 12 NEC-CC) extra independent samples. The most differentially expressed genes among these were CCND2, CXCR4, GPX3, CTNND1 DHCR7, DVL3, HSPB1 and TRIM28, which probably point to hypoxic conditions or a delayed oocyte maturation in NEC-CC samples. This opens up perspectives for new molecular embryo or oocyte selection parameters which might also be useful in countries where the selection has to be made at the oocyte stage before fertilization instead of at the embryonic stage.

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“…Direct studies, such as genomic or proteomic analyses, are difficult in human embryos, since such approaches remains invasive and might alter the embryo integrity [2]. Therefore ART laboratories need some indirect and non-invasive selection criteria [3]. …”

Section: Introductionmentioning

confidence: 99%

Semi-quantitative measurement of specific proteins in human cumulus cells using reverse phase protein array

Puard

Tranchant

Cadoret

et al. 2013

Reprod Biol Endocrinol

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BackgroundThe ability to predict the developmental and implantation ability of embryos remains a major goal in human assisted-reproductive technology (ART) and most ART laboratories use morphological criteria to evaluate the oocyte competence despite the poor predictive value of this analysis. Transcriptomic and proteomic approaches on somatic cells surrounding the oocyte (granulosa cells, cumulus cells [CCs]) have been proposed for the identification of biomarkers of oocyte competence. We propose to use a Reverse Phase Protein Array (RPPA) approach to investigate new potential biomarkers of oocyte competence in human CCs at the protein level, an approach that is already used in cancer research to identify biomarkers in clinical diagnostics.MethodsAntibodies targeting proteins of interest were validated for their utilisation in RPPA by measuring siRNA-mediated knockdown efficiency in HEK293 cells in parallel with Western blotting (WB) and RPPA from the same lysates. The proteins of interests were measured by RPPA across 13 individual human CCs from four patients undergoing intracytoplasmic sperm injection procedure.ResultsThe knockdown efficiency of VCL, RGS2 and SRC were measured in HEK293 cells by WB and by RPPA and were acceptable for VCL and SRC proteins. The antibodies targeting these proteins were used for their detection in human CCs by RPPA. The detection of protein VCL, SRC and ERK2 (by using an antibody already validated for RPPA) was then carried out on individual CCs and signals were detected for each individual sample. After normalisation by VCL, we showed that the level of expression of ERK2 was almost the same across the 13 individual CCs while the level of expression of SRC was different between the 13 individual CCs of the four patients and between the CCs from one individual patient.ConclusionsThe exquisite sensitivity of RPPA allowed detection of specific proteins in individual CCs. Although the validation of antibodies for RPPA is labour intensive, RRPA is a sensitive and quantitative technique allowing the detection of specific proteins from very small quantities of biological samples. RPPA may be of great interest in clinical diagnostics to predict the oocyte competence prior to transfer of the embryo using robust protein biomarkers expressed by CCs.

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Safer embryo tests could boost IVF pregnancy rates

Cited by 8 publications

References 4 publications

A non-invasive test for assessing embryo potential by gene expression profiles of human cumulus cells: a proof of concept study

A non-invasive test for assessing embryo potential by gene expression profiles of human cumulus cells: a proof of concept study

Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis

Semi-quantitative measurement of specific proteins in human cumulus cells using reverse phase protein array

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