New candidate genes to predict pregnancy outcome in single embryo transfer cycles when using cumulus cell gene expression

Wathlet, Sandra; Adriaenssens, Tom; Segers, Ingrid; Verheyen, Greta; Janssens, Ronny; Coucke, Wim; Devroey, Paul; Smitz, Johan

doi:10.1016/j.fertnstert.2012.05.007

Cited by 70 publications

(60 citation statements)

References 36 publications

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“…This model reached an accuracy of 93% for pregnancy prediction. However, in her previous study [14], there were three genes ( CAMK1D, EFNB2, STC1 ) expressed in CC proposed as biomarkers of pregnancy and only EFNB2 was retained in the pregnancy prediction model in the next study. Meanwhile, Iager et al .…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, several studies have tried to identify candidate genes expressed in somatic cells of ovarian follicles that could be used as biomarkers of oocyte and embryo quality [10,11] and successful embryo implantation [12,13,14,15]. However, the genes proposed as potential biomarkers show little overlap between different study groups.…”

Section: Introductionmentioning

confidence: 99%

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No Specific Gene Expression Signature in Human Granulosa and Cumulus Cells for Prediction of Oocyte Fertilisation and Embryo Implantation

et al. 2015

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In human IVF procedures objective and reliable biomarkers of oocyte and embryo quality are needed in order to increase the use of single embryo transfer (SET) and thus prevent multiple pregnancies. During folliculogenesis there is an intense bi-directional communication between oocyte and follicular cells. For this reason gene expression profile of follicular cells could be an important indicator and biomarker of oocyte and embryo quality. The objective of this study was to identify gene expression signature(s) in human granulosa (GC) and cumulus (CC) cells predictive of successful embryo implantation and oocyte fertilization. Forty-one patients were included in the study and individual GC and CC samples were collected; oocytes were cultivated separately, allowing a correlation with IVF outcome and elective SET was performed. Gene expression analysis was performed using microarrays, followed by a quantitative real-time PCR validation. After statistical analysis of microarray data, there were no significantly differentially expressed genes (FDR<0,05) between non-fertilized and fertilized oocytes and non-implanted and implanted embryos in either of the cell type. Furthermore, the results of quantitative real-time PCR were in consent with microarray data as there were no significant differences in gene expression of genes selected for validation. In conclusion, we did not find biomarkers for prediction of oocyte fertilization and embryo implantation in IVF procedures in the present study.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

No Specific Gene Expression Signature in Human Granulosa and Cumulus Cells for Prediction of Oocyte Fertilisation and Embryo Implantation

et al. 2015

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“…In recent years, advances using this approach have increasingly shown promise for predicting oocyte quality. [66][67][68] One of the challenges in using CC mRNA data is handling the considerable variability in expression values for individual candidate genes both within and between patients. 66 Recently, a multiplex quantitative polymerase chain reaction (QPCR) study using human CC identified four candidate genes that were associated with a significant improvement in predicting viable blastocysts and live birth outcomes relative to random selection of related meta phase II (MII) oocytes before intra cytoplasmic increase ovulation rate was that the additional treatment of supplementary gonadotropins in these animals failed to further augment the ovulatory response, 58 as has previously been observed in Inverdale ewes.…”

Section: Can Gene Expression Profiles In Cumulus Cells (Cc) Isolated mentioning

confidence: 99%

Oocyte-Somatic Cell Interactions and Ovulation Rate: Effects on Oocyte Quality and Embryo Yield

McNatty¹,

Juengel²,

Pitman³

2014

Reproductive Biology Insights

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ABSTRACT:The use of exogenous gonadotropins to increase oocyte yields for better pregnancy outcomes remains unpredictable and inefficient. The objectives of this review are to address two questions concerning this issue: (1) are there any alternatives for improving consistency in oocyte yields? (2) is it possible to develop a molecular diagnostic test for oocytes with blastocyst potential? Studies in sheep with a heterozygous inactivating mutation in the oocyte-derived growth factor, bone morphogenetic protein 15 (BMP15), report increased oocyte yields and significantly more offspring. Moreover, partial immuno-neutralization of BMP15 bioactivity increases oocyte yield without modifying gonadotropin or ovarian steroid secretion. Therefore, it is hypothesized that the development of BMP15 antagonists may prove them to be suitable alternatives to exogenous gonadotropins. Recent evidence from analyses of candidate gene expression in human cumulus cells separated from individual oocytes before IVF indicates a potential non-invasive molecular screen for oocytes with improved blastocyst and live-birth outcomes.

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“…In IVF the yield per oocyte collected is well below 10 % [31], and it is hard to believe that the oocyte is the primary reason for this. Transcriptome analysis of cumulus cells has been proposed as a non-invasive tool for determining the quality of the corresponding oocyte, but this raises a few questions [18,19,32].…”

Section: Discussionmentioning

confidence: 99%

Sequential (hFSH + recFSH) vs homogenous (hFSH or recFSH alone) stimulation: clinical and biochemical (cumulus cell gene expression) aspects

Gürgan

Montjean²,

Ménézo

2014

J Assist Reprod Genet

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FSH is a key hormone in the regulation of follicular development. Together with the EGF network, these molecules mediate oocyte maturation and competence in preparation for the action of LH. FSH isoforms regulate distinct biological pathways and have specific effects on granulosa cell function and maturation of the ovarian follicle. Their dynamic interactions occur during the follicular cycle; shortliving forms are predominant in the pre-ovulatory phase, whereas long-acting molecules characterize the lutealfollicular transition. Recombinant FSH (rFSH) molecules have a reduced number of isoforms and are less acidic, with a shorter half-life. We have investigated sequential stimulation, comparing hFSH + rFSH, vs. rFSH alone and hFSH alone for the entire stimulation phase. Sequential stimulation leads to an E2 per MII oocyte ratio that is much lower than is seen during treatment with the two drugs individually. Although there is a positive tendency in favor of the sequential treatment, there was no significant difference in pregnancy rates, even taking frozen embryos into consideration. The cumulus cell transcriptome varies considerably between the treatments, although with no clear significance. When comparing pregnant vs. non-pregnant patients, in general a decrease in mRNA expression can be observed in the pregnant patients, especially in expression of folic acid receptor 1 and ovostatin 2. This indicates that material has been transferred from CC to the oocyte. However, a common observation in the literature is that variations in the transcriptome of the cumulus cells are highly dependent upon the patient genotype; the potential for applying this strategy as a basis for selecting embryos is, at the very least, questionable.

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New candidate genes to predict pregnancy outcome in single embryo transfer cycles when using cumulus cell gene expression

Cited by 70 publications

References 36 publications

No Specific Gene Expression Signature in Human Granulosa and Cumulus Cells for Prediction of Oocyte Fertilisation and Embryo Implantation

No Specific Gene Expression Signature in Human Granulosa and Cumulus Cells for Prediction of Oocyte Fertilisation and Embryo Implantation

Oocyte-Somatic Cell Interactions and Ovulation Rate: Effects on Oocyte Quality and Embryo Yield

Sequential (hFSH + recFSH) vs homogenous (hFSH or recFSH alone) stimulation: clinical and biochemical (cumulus cell gene expression) aspects

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