Nuclear magnetic resonance metabolomic profiling of Day 3 and 5 embryo culture medium does not predict pregnancy outcome in good prognosis patients: a prospective cohort study on single transferred embryos

Kirkegaard, Kirstine; Svane, Anna S.P.; Nielsen, Jens Steen; Hindkjær, Johnny; Nielsen, Niels Chr.; Ingerslev, Hans Jakob

doi:10.1093/humrep/deu236

Cited by 36 publications

(22 citation statements)

References 32 publications

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“…Although promising, these approaches have still to consider the difficulties of their application on a daily/routine basis for assessing embryo competency. Alternative metabolomic approaches including nuclear magnetic resonance (NMR) and near-infrared spectroscopy (NIR) have not, to date, managed to successfully predict pregnancies (Hardarson et al 2012;Kirkegaard et al 2014).…”

Section: Metabolomics Of Spent Media and Reproductive Fluidsmentioning

confidence: 99%

Can trophectoderm RNA analysis predict human blastocyst competency?

Ntostis

Kokkali²,

Iles

et al. 2019

Systems Biology in Reproductive Medicine

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A systematic review of the literature showed that trophectoderm biopsy could assist in the selection of healthy embryos for uterine transfer without affecting implantation rates. However, previous studies attempting to establish the relationship between trophectoderm gene expression profiles and implantation competency using either microarrays or RNA sequencing strategies, were not sufficiently optimized to handle the exceptionally low RNA inputs available from biopsied material. In this pilot study, we report that differential gene expression in human trophectoderm biopsies assayed by an ultra-sensitive next generation RNA sequencing strategy could predict blastocyst implantation competence. RNA expression profiles from isolated human trophectoderm cells were analysed with established clinical pregnancy being the primary endpoint. Following RNA sequencing, a total of 47 transcripts were found to be significantly differentially expressed between the trophectoderm cells from successfully implanted (competent) versus unsuccessful (incompetent) blastocysts. Of these, 36 transcripts were significantly down-regulated in the incompetent blastocysts, including Hydroxysteroid 17-Beta Dehydrogenase 1 (HSD17B1) and Cytochrome P450 Family 11 Subfamily A Member 1 (CYP11A1), while the remaining 11 transcripts were significantly up-regulated, including BCL2 Antagonist/Killer 1 (BAK1) and KH Domain Containing 1 Pseudogene 1 (KHDC1P1) of which the latter was always detected in the incompetent and absent in all competent blastocysts. Ontological analysis of differentially expressed RNAs revealed pathways involved in steroidogenic processes with high confidence. Novel differentially expressed transcripts were also noted by reference to a de novo sequence assembly. The selection of the blastocyst with the best potential to support full-term pregnancy following single embryo transfer could reduce the need for multiple treatment cycles and embryo transfers. The main limitation was the low sample size (N = 8). Despite this shortcoming, the pilot suggests that trophectoderm biopsy could assist with the selection of healthy embryos for embryo transfer. A larger cohort of samples is needed to confirm these findings.Abbreviations: AMA: advanced maternal age; ART: assisted reproductive technology; CP: clinical pregnancy; DE: differential expression; FDR: false discovery rate; IVF: in vitro fertilization; LD PCR: long distance PCR; qRT-PCR: quantitative real-time PCR; SET: single embryo transfer; TE: trophectoderm

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Section: Metabolomics Of Spent Media and Reproductive Fluidsmentioning

confidence: 99%

Can trophectoderm RNA analysis predict human blastocyst competency?

Ntostis

Kokkali²,

Iles

et al. 2019

Systems Biology in Reproductive Medicine

View full text Add to dashboard Cite

show abstract

“…A number of studies have attempted to non-invasively measure embryo quality based on the metabolic signatures of the embryo culture media by using a variety of techniques1617181920. Nonetheless, the extension of these findings to clinical application remains clouded by conflicting reports21 and technical complexities. Our group has demonstrated that uptake of pyruvate by the human embryos from culture medium and pyruvate to alanine ratio on day 3 of development is predictive of implantation potential20.…”

mentioning

confidence: 99%

Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos

D’Souza

Pudakalakatti

Uppangala

et al. 2016

Sci Rep

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Early development of certain mammalian embryos is protected by complex checkpoint systems to maintain the genomic integrity. Several metabolic pathways are modulated in response to genetic insults in mammalian cells. The present study investigated the relationship between the genetic integrity, embryo metabolites and developmental competence in preimplantation stage mouse embryos with the aim to identify early biomarkers which can predict embryonic genetic integrity using spent medium profiling by NMR spectroscopy. Embryos carrying induced DNA lesions (IDL) developed normally for the first 2.5 days, but began to exhibit a developmental delay at embryonic day 3.5(E3.5) though they were morphologically indistinguishable from control embryos. Analysis of metabolites in the spent medium on E3.5 revealed a significant association between pyruvate, lactate, glucose, proline, lysine, alanine, valine, isoleucine and thymine and the extent of genetic instability observed in the embryos on E4.5. Further analysis revealed an association of apoptosis and micronuclei frequency with P53 and Bax transcripts in IDL embryos on the E4.5 owing to delayed induction of chromosome instability. We conclude that estimation of metabolites on E3.5 in spent medium may serve as a biomarker to predict the genetic integrity in pre-implantation stage embryos which opens up new avenues to improve outcomes in clinical IVF programs.

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“…More recently, a prospective cohort study analyzed the spent culture media on day-3 and on day-5 from 148 single transferred blastocysts. Despite of a high degree of individual metabolomic variation, no correlation was found with pregnancy outcome (49). On the contrary, a study performed on 621 frozen-thawed embryos transferred on day 4 revealed that metabolomic profiling of spent culture media is independent of morphology and correlates with implantation potential (50).…”

Section: Metabolomic Profilingmentioning

confidence: 96%

Unconventional embryo selection strategies: a look into the future

Maria¹

2016

CCE

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SummaryThe assessment of an unequivocal method able to identify the embryo with the higher possibility to implant, leading to a single live birth, is crucial for the success of an infertility treatment. Standard morphology evaluation, morphokinetic analysis and preimplantation genetic screening are the more employed embryo selection strategies in reproductive medicine centers. However, the results and the applicability of these methodologies are still controversial. Therefore, there is the need to find additional technologies to clinically select developing embryos. The challenge is to set-up a predictive, not invasive, reproducible, objective and effective method able to select the best embryo. In this review, we present several unconventional methodologies of embryo evaluation, analyzing their possible future application in human reproduction.

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Nuclear magnetic resonance metabolomic profiling of Day 3 and 5 embryo culture medium does not predict pregnancy outcome in good prognosis patients: a prospective cohort study on single transferred embryos

Abstract: NCT01139268.

Cited by 36 publications

References 32 publications

Can trophectoderm RNA analysis predict human blastocyst competency?

Can trophectoderm RNA analysis predict human blastocyst competency?

Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos

Unconventional embryo selection strategies: a look into the future

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