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Hardarson T.,Fertilitetscentrum | Ahlstrm A.,Fertilitetscentrum | Rogberg L.,Fertilitetscentrum | Botros L.,Molecular Biometrics | And 4 more authors.
Human Reproduction | Year: 2012

BACKGROUND: Near infrared (NIR) spectroscopy is a technology proposed to facilitate non-invasive screening for the most optimal human embryo for uterine transfer. It has been proposed that the NIR spectral profile of an embryos spent culture medium can be used to generate a viability score that correlates to implantation potential. As the initial proof of principle studies were all retrospective, our aim was to investigate whether NIR spectroscopy on spent embryo culture medium in an on-site, prospective setting could improve the ongoing single embryo transfer (SET) pregnancy rate after Day 2 and 5 transfers. METHODS: We conducted a single-centre, double-blinded, randomized controlled trial in which the NIR group was compared with a control group. The primary outcome was the clinical pregnancy rate after 67 weeks of gestation per randomized patient. In the control group embryo selection was based only on traditional morphological evaluation while in the treatment group NIR spectroscopy was added to the morphological evaluation. RESULTS: The study was terminated early as the analysis of the Data Safety Monitoring Board showed a very low conditional power of superiority for the primary outcome. Of the 752 patients calculated to be included in the study, 164 and 163 patients were randomized into the NIR and control groups, respectively. No significant difference in the ongoing pregnancy rate per randomized patient was found between the NIR and the control group, 34.8 versus 35.6, (P 0.97). The proportional difference between the study groups mean was -0.8 (95 confidence interval 11.4 to 10.2). CONCLUSIONS: This study shows that adding NIR spectroscopy, in its present form, to embryo morphology does not improve the chance of a viable pregnancy when performing SET. The NIR technology appears to need further development before it can be used as an objective marker of embryo viability. © The Author 2011.


Seli E.,Yale University | Bruce C.,Yale University | Botros L.,Molecular Biometrics | Henson M.,Molecular Biometrics | And 12 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2011

Purpose: Assessment of embryo viability is a key component of in vitro fertilization (IVF) and currently relies largely on embryo morphology and cleavage rate. In this study, we used receiver operating characteristic (ROC) analysis to compare the Viability Score (generated by metabolomic profiling of spent embryo culture media using near infrared (NIR) spectroscopy) to morphologic grading for predicting pregnancy in women undergoing single embryo transfer (SET) on day 5. Methods: A total of 198 spent embryo culture media samples were collected in four IVF centers located in the USA, Europe and Australia. First, 137 samples (training set) were analyzed by NIR to develop an algorithm that generates a Viability Score predictive of pregnancy for each sample. Next, 61 samples (validation set) were analyzed by observers blinded to embryo morphology and IVF outcome, using the Day 5 algorithm generated with the training set. Pregnancy was defined as fetal cardiac activity (FCA) at 12 weeks of gestation. Results: The Area Under the Curve (AUC) was greater for the metabolomic Viability Score compared to Morphology [Training set: 0.75 versus 0.55, p=0.0011; Validation set: 0.68 versus 0.50, P=0.021], and for a Composite score (obtained using a model combining Viability Score with morphologic grading), compared to morphology alone [0.74 versus 0.50, p=0.004]. Conclusions: Our findings suggest that Viability Score alone or in combination with morphologic grading has the potential to be a better classifier for pregnancy outcome than morphology alone in women undergoing SET on day 5. © 2010 Springer Science+Business Media, LLC.


Vergouw C.G.,VU University Amsterdam | Botros L.L.,Molecular Biometrics | Judge K.,Molecular Biometrics | Henson M.,Molecular Biometrics | And 7 more authors.
Reproductive BioMedicine Online | Year: 2011

This study investigated if metabolomic profiling of culture media using near infrared (NIR) spectroscopy was related to live-birth rates after single-embryo transfer of frozen-thawed embryos. Analysis of culture media of frozen-thawed embryos was performed by NIR spectroscopy. A viability score was calculated using a predictive multivariate algorithm of fresh day-5 embryos with known pregnancy outcomes. This algorithm generated with fresh day-5 embryos could help to identify the live-birth group from the no live-birth group. Multivariable regression models that tested the predictive ability of the viability score for live birth showed an odds ratio in the crude analysis of 1.50 (P = 0.008), after adjustment for embryo morphology, 1.44 (P = 0.022), and after adjustment for all variables, 1.71 (P = 0.005); based on a 0.1 step increase in viability scores. In conclusion, higher viability scores resulted in higher live-birth rates. An algorithm generated from fresh embryos might be used to predict viability of frozen-thawed embryos. Frozen-thawed embryos have different metabolic activity which is related to implantation potential. Therefore, this method might be useful to select the best embryo for transfer within a group of embryos with similar morphology. In frozen-thawed embryo transfer (FET) cycles, usually more than one embryo is transferred. However, elective single embryo transfer (SET) might be effective in FET cycles when a good-quality embryo is selected. Viability assessment of frozen-thawed embryos is usually performed by morphological assessment. Although very helpful, morphological assessment remains subjective and can be unreliable in predicting embryo viability. New parameters to predict embryo viability, including non-invasive metabolomic profiling, have recently been studied. Metabolomics is the study of small-molecule metabolite byproducts left behind from cellular processes. By measuring byproducts of the embryonic metabolism in spent embryo culture media, a snapshot of the physiology of an embryo is obtained, which translates to viability. In this study, we investigated if metabolomic profiling by near infrared (NIR) spectroscopy was related to live-birth rates after SET of frozen-thawed embryos. Analysis of spent culture media of frozen-thawed embryos was performed by NIR spectroscopy and a viability score was calculated. The mean viability score from embryos with known implantation potential was significantly higher than the mean viability score of embryos which failed to implant: i.e. higher viability scores resulted in higher live-birth rates. Individual embryos showed a positive relationship between increased viability scores and increased live-birth rates. In other words, frozen-thawed embryos (of the same morphological grade) have different metabolic activity which is related to implantation potential. This indicates that the use of morphological and metabolomic criteria can both help with the decision of which embryo to transfer after thawing. © 2011 Elsevier Inc. All rights reserved.


Seli E.,Yale University | Vergouw C.G.,VU University Amsterdam | Morita H.,Kato Ladies Clinic | Botros L.,Molecular Biometrics | And 6 more authors.
Fertility and Sterility | Year: 2010

Objective: To determine whether metabolomic profiling of spent embryo culture media correlates with reproductive potential of human embryos. Design: Retrospective study. Setting: Academic and a private assisted reproductive technology (ART) programs. Patient(s): Women undergoing single embryo transfer after IVF. Intervention(s): Spent embryo culture media were collected after single embryo transfer on day 3 (n = 304) or day 2 (n = 181) and analyzed by near infrared spectroscopy. Near infrared spectral regions were correlated to reproductive potential using a genetic algorithm optimization. Models of these spectral regions were used to calculate viability indices, and were validated by blinded analysis of a subset (n = 60) of samples. Implantation rates were also compared between embryos of higher (≥0.3) and lower (<0.3) viability indices, and within each morphology grade. Main Outcome Measure(s): Viability index and embryo viability. Result(s): Mean viability indices of embryos that resulted in positive fetal cardiac activity were significantly higher compared with embryos that did not for both day 2 and day 3 embryos. Blinded validation of the day 2 model proved to be significant. Increasing viability index values correlated with an increase in pregnancy. Viability indices were found to be independent of morphology for both day 2 and day 3 embryos. Implantation rates were significantly higher among embryos with viability indices ≥0.3. Conclusion(s): Metabolomic profiling of human embryo culture media using near infrared spectroscopy is independent of morphology and correlates with reproductive potential of embryos. © 2010 American Society for Reproductive Medicine.


Vergouw C.G.,VU University Amsterdam | Kieslinger D.C.,VU University Amsterdam | Kostelijk E.H.,VU University Amsterdam | Botros L.L.,Molecular Biometrics | And 4 more authors.
Human Reproduction | Year: 2012

study question: Is the selection of a single Day 3 embryo by metabolomic profiling of culture medium with near-infrared (NIR) spectroscopy as an adjunct to morphology able to improve live birth rates in IVF, compared with embryo selection by morphology alone? summary answer: The live birth rate after embryo selection by NIR spectroscopy and morphology is not significantly different compared with the live birth rate after embryos were selected by morphology alone. what is known already: The elevated incidence of pregnancy and neonatal problems associated with a high-twinning rate after IVF can only be successfully reduced by the transfer of one embryo. Current embryo assessment methods are unable to accurately predict the reproductive potential of an individual embryo. Today, a number of techniques are said to be more accurate at selecting the best embryo. One of these new technologies is metabolomic profiling of spent embryo culture media with the use of NIR spectroscopy. study design, size and duration: A double-blind, randomized controlled trial was conducted between 2009 and 2011, and included 417 couples undergoing IVF with a single embryo transfer. Randomization was performed centrally just before Ovum Pick-Up (OPU), using a computerized randomization program. Both patient and physician were unaware of the treatment allocation. To ensure blinding, the allocations were placed in consecutively numbered, opaque envelopes. Patients were randomized (1:1) into either the control group (embryo selection by morphology only) or the treatment group (embryo selection by morphology plus NIR spectroscopy of embryo culture medium). participants/materials, setting and methods: At OPU, 208 patients were randomized to the morphology only group and 209 patients were randomized to the morphology plus viability score group. On Day 3, 163 patients in the control group and 146 patients in the treatment group met the inclusion criteria. The study was conducted in an academic hospital with IVF laboratory and three non-academic hospitals. main results and the role of chance: Patient demographics and baseline characteristics were distributed equally over the two groups, except for embryo fragmentation, which was significantly higher in the treatment group. In the intention to treat analysis, the live birth rates were 31.7 and 26.8% for the control group and the treatment group, respectively (relative risk 0.84; 95% confidence interval 0.63-1.14, P = 0.27). In the per protocol analysis, the live birth rates were 31.3 and 29.5% for the control group and the treatment group, respectively (relative risk 0.94; 95% confidence interval 0.67-1.32, P = 0.73). For the treatment group, the embryological technician's independent choice (by morphology) of which embryo to transfer was recorded 138 times. In 75.4% (104 of 138) of the transfers, the embryo with the best morphology did not have the highest viability score. The live birth rate of these 104 transferred embryos was 30.8%. limitations, reasons for caution: A possible limitation of our study is the pre-selection of all embryos by morphology and dividing the cohort of available embryos into two groups: good quality embryos and poor quality embryos. As a consequence, we have probably selected for a better prognosis patient group. wider implications of the findings: To avoid the use of incompetent embryo selection tools at the expense of the patient, an evidence-based proof of clinical usefulness is essential before the implementation of new diagnostic tools in IVF laboratories. trial registration numbers: Dutch Trial Registry, registry number NTR1178. © The Author 2012.


Sakkas D.,Yale University | Sakkas D.,Molecular Biometrics | Alvarez J.G.,Instituto Marques | Alvarez J.G.,Harvard University
Fertility and Sterility | Year: 2010

Objective: To review the mechanisms responsible for DNA fragmentation in human sperm, including those occurring during spermatogenesis and transport through the reproductive tract. The mechanisms examined include: apoptosis in the seminiferous tubule epithelium, defects in chromatin remodeling during the process of spermiogenesis, oxygen radical-induced DNA damage during sperm migration from the seminiferous tubules to the epididymis, the activation of sperm caspases and endonucleases, damage induced by chemotherapy and radiotherapy, and the effect of environmental toxicants. The different tests currently used for sperm DNA fragmentation analysis and the factors that determine the predictive value of sperm DNA fragmentation testing and their implications in the diagnosis and treatment of infertility are also discussed. Finally, we also scrutinize how the presence in the embryonic genome of DNA strand breaks or modifications of DNA nucleotides inherited from the paternal genome could impact the embryo and offspring. In particular we discuss how abnormal sperm could be dealt with by the oocyte and how sperm DNA abnormalities, which have not been satisfactorily repaired by the oocyte after fertilization, may interfere with normal embryo and fetal development. Conclusion(s): Sperm DNA can be modified through various mechanisms. The integrity of the paternal genome is therefore of paramount importance in the initiation and maintenance of a viable pregnancy both in a natural conception and in assisted reproduction. The need to diagnose sperm at a nuclear level is an area that needs further understanding so that we can improve treatment of the infertile couple. © 2010 American Society for Reproductive Medicine.


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Molecular Biometrics | Date: 2010-11-02

Medical diagnostic assay for use in testing embryo viability in connection with in vitro fertilization procedures.


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Monthly Archives: August 2015 molecular mixology molecular gastronomy kits


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