Non-invasive metabolomic profiling of Day 2 and 5 embryo culture medium: a prospective randomized trial

Hardarson, Thorir; Ahlström, Aisling; Rogberg, Lena; Botros, Lucy; Hillensjö, T.; Westlander, Göran; Sakkas, Denny; Wikland, Matts

doi:10.1093/humrep/der373

Cited by 144 publications

(96 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…aneuploidy screening (PGS), O 2 respiration measurement, metabolic profiling and gene expression analysis [1,3,17,22,29,35,37]. Some of these methods, though promising, are not yet applicable in a routine clinical setting, and others, such as PGS and near infrared spectroscopy (NIR) analysis have been disappointing in their present form, when evaluated in large randomized clinical trials [10,11,22,34,38].…”

Section: Discussionmentioning

confidence: 99%

A randomized clinical trial comparing embryo culture in a conventional incubator with a time-lapse incubator

Kirkegaard

Hindkjær

Grøndahl

et al. 2012

J Assist Reprod Genet

129

View full text Add to dashboard Cite

Purpose Time-lapse monitoring allows for a flexible embryo evaluation and potentially provides new dynamic markers of embryo competence. Before introducing timelapse monitoring in a clinical setting, the safety of the instrument must be properly documented. Accordingly, the aim of this study was to evaluate the safety of a commercially available time-lapse incubator. Methods In a two center, randomized, controlled, clinical trial 676 oocytes from 59 patients in their 2nd or third treatment cycle, age <38 years and ≥8 oocytes retrieved were cultured in the time-lapse incubator or in a conventional incubator. The primary outcome was proportion of 4-cell embryos on day 2. Secondary outcomes were proportion of 7-8 cell embryos on day 3 and proportion of blastocysts on day 5. Implantation pregnancy rates were registered based on presence of fetal heart activity visualized by ultrasound 8 weeks after embryo transfer. Results No significant difference was found between the time-lapse incubator (TLI) and conventional incubator (COI) in proportion of 4-cell embryos on day 2 irrespective of whether data was analyzed according to ITT (RR TLI/COI : 0.81 (0.65; 1.02)) or PP (RR TLI/COI : 0.80 (0.63; 1.01)). Nor were any significant differences detected in the secondary endpoints; i.e. proportion of 7-8-cell embryos on day three ITT (RR TLI/COI : 0.96 (0.73; 1.26)); PP (RR TLI/COI : 0.95 (0.72; 1.26)) and proportion of blastocysts on day five ITT (RR TLI/COI : 1.09 (0.84; 1.41)); PP (RR TLI/COI : 1.09 (0.83: 1.41)). We found no differences in clinical pregnancy rate or implantation rate. Conclusion Culture in the time-lapse incubator supports embryonic development equally to a conventional incubator.

show abstract

Section: Discussionmentioning

confidence: 99%

A randomized clinical trial comparing embryo culture in a conventional incubator with a time-lapse incubator

Kirkegaard

Hindkjær

Grøndahl

et al. 2012

J Assist Reprod Genet

129

View full text Add to dashboard Cite

show abstract

“…Generally, embryo assessment is limited to static microscopic evaluations [17][18][19]. Alternative selection methods include genetic screening [20][21][22], morphokinetics [23], metabolomics [24,25], proteomics, oxygen consumption measurement and birefringence imaging [26]. The daily application of these innovating techniques is limited as they are invasive, complex, time-consuming, expensive and/or not yet proven to be superior to the static morphological evaluations, in particular compared to blastocyst culture [27].…”

Section: Introductionmentioning

confidence: 99%

Developmental capacity and pregnancy rate of tetrahedral- versus non-tetrahedral-shaped 4-cell stage human embryos

Cauffman

Verheyen

Tournaye

2014

J Assist Reprod Genet

View full text Add to dashboard Cite

Purpose The arrangement of the blastomeres within the 4-cell stage embryo reflects the orientation of the cleavage planes during the second division. To examine their relevance, the developmental capacity and the pregnancy rate were compared between tetrahedral-shaped and non-tetrahedralshaped 4-cell stage human embryos. Methods The study included 3,546 4-cell stage embryos. The arrangement of the blastomeres at the 4-cell stage was annotated as being tetrahedral or non-tetrahedral on day 2 of preimplantation development. Embryo quality was compared on day 3 and day 5. Pregnancy rates were calculated per single embryo transfer on day 3 or day 5. Results In total, 2,803 4-cell stage embryos (79 %) displayed a tetrahedral arrangement and 743 (21 %) displayed a non-tetrahedral arrangement. Tetrahedralshaped embryos developed more into high-quality embryos on day 3 (p<0.001) and day 5 (p=0.036) and had a higher blastulation rate (p=0.009). Though, the number of high-quality embryos selected for transfer did not differ between both groups on day 3 (p=0.167) and day 5 (p~1). Three hundred thirty single embryo transfers were analysed. No significant difference in clinical pregnancy was found between both groups after transfer on day 3 (p=0.209) and day 5 (p=0.653). Conclusions The arrangement of the blastomeres according to their previous cleavage planes was correlated to the developmental potential of the 4-cell stage embryo up to the blastocyst stage. If embryo transfers are performed on day 3 and day 5 of development using embryos of adequate quality, the blastomere arrangement at the 4-cell stage had no predictable value regarding pregnancy success.

show abstract

“…There are controversial studies regarding the viability index of oocytes/embryos established by metabolomic tests based on spectroscopy methods as a stronger predictor of implantation potential than traditional morphological assessment (Nagy et al 2008, Ahlstrom et al 2011, Hardarson et al 2012. However, in this MS study, the patients with positive implantation had embryos with significantly higher morphological quality, which suggests that morphology is still valuable and should be evaluated as an adjunct parameter .…”

Section: Discussionmentioning

confidence: 72%

“…In this study, we applied direct fingerprinting by ESI-Q-ToF-MS. MS fingerprinting analysis has been applied to a variety of biological models and even for bovine embryo culture medium quality control (Sawaya et al 2004, Marques et al 2006, de Souza et al 2007a, 2007b, Souza et al 2008, Ferreira et al 2009, Saraiva et al 2009). Although diverse analytical techniques that are primarily based on spectroscopy technologies, such as near-infrared, RAMAN, and proton NMR, have been used as noninvasive tools to predict embryo viability (Seli et al 2007, Nagy et al 2008, Scott et al 2008, Ahlstrom et al 2011, Hardarson et al 2012, to our knowledge, this is the first report that uses MS fingerprinting to predict human embryo implantation potential. Whereas spectroscopic techniques are based on the measurement of physical events resulting from the interaction of organic molecules with electromagnetic radiation, MS characterizes the molecular composition of a sample (Ferreira et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…These approaches include the measurement of glucose, lactate, pyruvate, or amino acid levels in the embryo culture media, as well as the assessment of oxygen consumption by the embryo, and genomic and proteomic profiling (Gardner et al 2001, Houghton et al 2002, Brison et al 2004, Lopes et al 2005, Dominguez et al 2008, Katz-Jaffe et al 2009). Most recently, analytical examination of the embryonic metabolome (Seli et al 2007, Bromer & Seli 2008, Scott et al 2008, Katz-Jaffe et al 2009, Aydiner et al 2010, Ferreira et al 2010, Ahlstrom et al 2011, Cortezzi et al 2011, Hardarson et al 2012 has also been evaluated, particularly applying spectroscopy methods. The metabolome refers to the complete stock of small compounds, such as metabolic intermediates and signaling molecules that are found within a biological sample.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prediction of embryo implantation potential by mass spectrometry fingerprinting of the culture medium

Cortezzi¹,

Cabral²,

Trevisan³

et al. 2013

Reproduction

View full text Add to dashboard Cite

This study has evaluated the performance of a multivariate statistical model to predict embryo implantation potential by processing data from the chemical fingerprinting of culture medium samples used for human embryo culture. The culture medium for 113 embryos from 55 patients undergoing ICSI was collected after embryo transfer. The samples were split into positive (nZ29) and negative (nZ84) implantation groups according their implantation outcomes (100% or 0% implantation). The samples were individually diluted and analyzed by electrospray ionization mass spectrometry (ESI-MS). The m/z ratios and relative abundances of the major ions in each spectrum were considered for partial least square discriminant analysis. Data were divided into two subsets (calibration and validation), and the models were evaluated and applied to the validation set. A total of 5987 ions were observed in the groups. The multivariate statistical model described more than 82% of the data variability. Samples of the positive group were correctly identified with 100% probability and negative samples with 70%. The culture media used for embryos that were positive or negative for successful implantation showed specific biochemical signatures that could be detected in a fast, simple, and noninvasive way by ESI-MS. To our knowledge, this is the first report that uses MS fingerprinting to predict human embryo implantation potential. This biochemical profile could help the selection of the most viable embryo, improving single-embryo transfer and thus eliminating the risk and undesirable outcomes of multiple pregnancies.

show abstract

Non-invasive metabolomic profiling of Day 2 and 5 embryo culture medium: a prospective randomized trial

Cited by 144 publications

References 17 publications

A randomized clinical trial comparing embryo culture in a conventional incubator with a time-lapse incubator

A randomized clinical trial comparing embryo culture in a conventional incubator with a time-lapse incubator

Developmental capacity and pregnancy rate of tetrahedral- versus non-tetrahedral-shaped 4-cell stage human embryos

Prediction of embryo implantation potential by mass spectrometry fingerprinting of the culture medium

Contact Info

Product

Resources

About