Balaban B.,American Hospital |
Brison D.,St Marys Hospital |
Calderon G.,IVI Barcelona |
Catt J.,Optimal IVF |
And 18 more authors.
Human Reproduction | Year: 2011
BACKGROUND: Many variations in oocyte and embryo grading make inter-laboratory comparisons extremely difficult. This paper reports the proceedings of an international consensus meeting on oocyte and embryo morphology assessment. Methods Background presentations about current practice were given. Results The expert panel developed a set of consensus points to define the minimum criteria for oocyte and embryo morphology assessment. CONCLUSIONS It is expected that the definition of common terminology and standardization of laboratory practice related to embryo morphology assessment will result in more effective comparisons of treatment outcomes. This document is intended to be referenced as a global consensus to allow standardized reporting of the minimum data set required for the accurate description of embryo development. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
PubMed | Centro Ginecologico Santiago Dexeus, Institute Universitari Dexeus, Quiron Barcelona, Ginefiv and 8 more.
Type: Journal Article | Journal: Fertility and sterility | Year: 2014
To investigate the impact of early cleavage (EC) on embryo quality, implantation, and live-birth rates.Prospective cross-sectional study.Multicenter study.Seven hundred embryo transfers and 1,028 early-stage human embryos.None.Implantation according to the presence of EC and embryo quality.The presence of EC is associated with embryo quality, especially in cycles with autologous oocytes. However, the use of EC as an additional criterion for selecting an embryo for transfer does not appear to significantly improve likelihood of implantation. Furthermore, embryos that presented EC had live-birth rates per implanted embryo similar to those that did not show any sign of cleavage.At least for conventional embryo culture and morphologic evaluations, the additional evaluation of EC in embryos may not be valuable to improve embryo implantation.
Esbert M.,IVI Barcelona |
Pacheco A.,IVI Madrid |
Vidal F.,University of Barcelona |
Florensa M.,IVI Barcelona |
And 4 more authors.
Reproductive BioMedicine Online | Year: 2011
A prospective study was performed to assess the impact of sperm DNA fragmentation on the outcome of IVF with own or donated oocytes. The study population included 178 couples (62 cycles of IVF, 116 of intracytoplasmic sperm injection (ICSI)) with own (n = 77) and donor (n = 101) oocytes. DNA fragmentation was evaluated by TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling assay. Correlation between DNA damage to oocyte fertilization, embryo quality and clinical pregnancy, implantation and miscarriage rates was evaluated. DNA fragmentation was not related to fertilization rates in either IVF (r = 0.08) or ICSI (r = -0.04) cycles. DNA fragmentation was similar in patients with <50% embryo utilization rate compared with ≥50%, in cancelled and in embryo transfer cycles and in miscarriages and in successful deliveries. Moreover, DNA fragmentation was similar in pregnant and non-pregnant women as well as in IVF with own or donor oocytes. In the multivariable analysis, the odds ratio of DNA after controlling by age was 1.0. Using a 36% sperm fragmentation threshold, results did not vary. It is concluded that DNA damage was not related to outcomes of IVF or ICSI with own or donor oocytes. Any form of sperm chromatin abnormalities or DNA damage may result in male infertility. The study of sperm DNA damage is especially relevant in an era in which advanced forms of assisted reproductive technologies are frequently used and in which barriers to natural selection are bypassed. A prospective study was carried out with the aim of assessing the impact of sperm DNA fragmentation on the outcome of IVF with own or donated oocytes. We studied 178 couples undergoing 62 cycles of IVF and 116 of intracytoplasmic sperm injection (ICSI) with own (n = 77) and donor (n = 101) oocytes. DNA fragmentation was evaluated by TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling assay. Oocyte fertilization, embryo quality and pregnancy, implantation and miscarriage rates were correlated with DNA damage. DNA fragmentation was not related to fertilization rates in either IVF (r = 0.08) or ICSI (r = -0.04) cycles. DNA fragmentation was higher in patients with <50% of good-quality embryos than with ≥50%, in cancelled than in embryo transfer cycles and in miscarriages than in successful deliveries. DNA fragmentation was similar in pregnant and non-pregnant women as well as in IVF with own or donor oocytes. In the logistic regression analysis, the odds ratio of DNA after controlling by age was 1.0. Using a 36% sperm fragmentation cut-off point, results did not vary. According to these findings, it can be concluded that DNA damage was not related to outcomes of IVF or ICSI with own or donor oocytes. © 2011 Elsevier Inc. All rights reserved.
Sanchez-Ribas I.,IVI Barcelona |
Sanchez-Ribas I.,University of Valencia |
Riqueros M.,IVI Barcelona |
Vime P.,IVI Seville |
And 6 more authors.
Fertility and Sterility | Year: 2012
Objective: To investigate the metabolomic signature of trisomy 21 preimplantation human embryos by a noninvasive approach using mass spectrometry- (MS-) and nuclear magnetic resonance spectroscopy- (NMR-) based metabolic profiling platforms. Design: A total of 171 spent media samples were collected from day 3 embryos and comparatively analyzed by MS analysis (chromosomally normal embryos, n = 15; trisomy 21 embryos, n = 15) and a matched control media group (without embryo, n = 14) and by NMR spectroscopy (normal embryos, n = 39; trisomy 21 embryos, n = 35; monosomy 21 embryos, n = 24) and a matched control media group (without embryo, n = 29). Setting: IVF clinic/preimplantation genetic diagnosis (PGD) unit facilities. Patient(s): One hundred seventy-one spent media samples obtained from human IVF embryos from patients included in our PGD program. Intervention(s): Metabolomic profiling of embryo spent media using liquid chromatography/gas chromatography coupled with MS and NMR. Main Outcome Measure(s): Comparative identification of the metabolites present in the spent media from normal versus trisomy/monosomy 21 day 3 embryos. Result(s): Two metabolites, caproate and androsterone sulphate, and two unknown compounds were differentially expressed between normal and trisomy 21 day 3 embryos. Furthermore, the NMR results indicate that there could be a correlation between the differences found between trisomy 21/monosomy 21 and the normal embryos in a spectral region compatible with isoleucine. Conclusion(s): This study suggests that the use of differential metabolomic markers found in spent media from preimplantation embryos could be a feasible method for the detection of aneuploidies before ET. Copyright © 2012 American Society for Reproductive Medicine, Published by Elsevier Inc.
Basile N.,IVI Madrid |
Nogales M.D.C.,IVI Madrid |
Bronet F.,IVI Madrid |
Florensa M.,IVI Barcelona |
And 4 more authors.
Fertility and Sterility | Year: 2014
Objective To study the differences in the cleavage time between chromosomally normal and abnormal embryos and to elaborate an algorithm to increase the probability of noninvasively selecting chromosomally normal embryos. Design Retrospective cohort study. Setting University-affiliated infertility center. Patient(s) Preimplantation genetic screening patients (n = 125; n = 77 with ET), including cases of repeated implantation failure or recurrent miscarriage. A total of 504 embryos were analyzed. Intervention(s) Embryo culture within a time-lapse system. Main Outcome Measure(s) Kinetic variables included the time to 2 (t2), 3 (t3), 4 (t4), and 5 (t5) cells as well as the length of the second (cc2 = t3 - t2) and third (cc3 = t5 - t3) cell cycle, the synchrony in the division from 2 to 4 cells (s2 = t4 - t3), and the interval t5 - t2. Implantation and clinical pregnancy rates were also analyzed. Result(s) A logistic regression analysis identified t5 - t2 (odds ratio [OR] = 2.853; 95% confidence interval [CI], 1.763-4.616), followed by cc3 (OR = 2.095; 95% CI, 1.356-3.238) as the most relevant variables related to normal chromosomal content. On the basis of these results, an algorithm for embryo selection is proposed to classify embryos from A to D. Each category exhibited significant differences in the percentage of normal embryos (A, 35.9%; B, 26.4%; C, 12.1%; D, 9.8%). Conclusion(s) Chromosomally normal and abnormal embryos have different kinetic behavior. On the basis of these differences, the proposed algorithm serves as a tool to classify embryos and to increase the probability of noninvasively selecting normal embryos. © 2014 American Society for Reproductive Medicine, Published by Elsevier Inc.
Basile N.,IVI Madrid |
Vime P.,IVI Seville |
Florensa M.,IVI Barcelona |
Aparicio Ruiz B.,IVI Valencia |
And 3 more authors.
Human Reproduction | Year: 2015
study question: Canweuse morphokinetic markers to select the embryos most likely to implant and are the results likely to be consistent across different clinics? summary answer: Yes, morphokinetic markers can be used to select the embryos most likely to implant and the results were similar in different IVF clinics that share methods and organization to some extent. what is known already:With the introduction of time-lapse technology several authors have proposed the use of kinetic markers to improve embryo selection. The majority of these markers can be detected as early as Day 2 of development. Morphology remains the gold standard but kinetic markers have been proven as excellent tools to complement our decisions. Nevertheless, the majority of time-lapse studies are based on small data sets deriving from one single clinic. study design, size, duration: Retrospective multicentric study of 1664 cycles of which 799 were used to develop an algorithm (Phase 1 of the study) and 865 to test its predictive power (Phase 2 of the study). participants/materials, setting, methods: University-affiliated infertility centres patients undergoing first or second ICSI cycle using their own or donated oocytes. Embryo development was analysed with a time-lapse imaging system. Variables studied included the timing to two cells (t2), three cells (t3), four cells (t4) and five cells (t5) as well as the length of the second cell cycle (cc2 = t3 2 t2) and the synchrony in the division from two to four cells (s2 = t4 2 t3). Implantation (IR) and clinical pregnancy (CPR) rates were also analysed. main results and the role of chance: During Phase 1 of the studywe identified three variables most closely related to implantation: t3 (34-40 h), followed by cc2 (9-12 h) and t5 (45-55 h). Based on these results we elaborated an algorithm that classified embryos from A to D according to implantation potential. During Phase 2 of the study the algorithm was validated in a different group of patients that included 865 cycles and 1620 embryos transferred. In this phase of the study, embryoswere categorized based on the algorithm and significant differences in IR were observed between the different categories ('A' 32%, 'B' 28%, 'C' 26%, 'D' 20% and 'E' 17%, P < 0.001). In addition we identified three quality criteria: direct cleavage from one to three cells, uneven blastomere size in second cell cycle and multinucleation in third cell cycle. limitations, reasons for caution: The retrospective nature of the study limits its potential value, although the use of one database to generate the algorithm (embryos from this database were not selected by any morphokinetic criteria) and one database to validate it reinforces our conclusions. wider implications of the findings: The elaboration of an algorithm based on a larger database derived from different (albeit related) clinics raises the possibility that such algorithms could be applied in different clinical settings. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
Costa-Borges N.,Embryotools |
Belles M.,IVI Barcelona |
Meseguer M.,IVI Valencia |
Galliano D.,IVI Barcelona |
And 2 more authors.
Fertility and Sterility | Year: 2016
Objective To evaluate the efficiency of using a continuous (one-step) protocol with a single medium for the culture of human embryos in a time-lapse incubator (TLI). Design Prospective cohort study on sibling donor oocytes. Setting University-affiliated in vitro fertilization (IVF) center. Patient(s) Embryos from 59 patients. Intervention(s) Culture in a TLI in a single medium with or without renewal of the medium on day-3. Main Outcome Measure(s) Embryo morphology and morphokinetic parameters, clinical pregnancy, take-home baby rate, and perinatal outcomes. Result(s) The blastocyst rates (68.3 vs. 66.8%) and the proportion of good-quality blastocysts (transferred plus frozen) obtained with the two-step (80.0%) protocol were statistically significantly similar to those obtained in the one-step protocol (72.2%). Similarly, morphokinetic events from early cleavage until late blastocyst stages were statistically significantly equivalent between both groups. No differences were found either in clinical pregnancy rates when comparing pure transfers performed with embryos selected from the two-step (75.0%), one-step (70.0%, respectively), and mixed (57.1%) groups. A total of 55 out of 91 embryos transferred implanted successfully (60.4%), resulting in a total of 37 newborns with a comparable birth weight mean among groups. Conclusion(s) Our findings support the idea that in a TLI with a controlled air purification system, human embryos can be successfully cultured continuously from day 0 onward in single medium with no need to renew it on day-3. This strategy does not affect embryo morphokinetics or development to term and offers more stable culture conditions for embryos as well as practical advantages and reduced costs for the IVF laboratory. © 2016 American Society for Reproductive Medicine.
Busso C.,IVI Valencia |
Fernandez-Sanchez M.,IVI Seville |
Garcia-Velasco J.A.,University of Santiago de Compostela |
Landeras J.,IVI Murcia |
And 6 more authors.
Human Reproduction | Year: 2010
Background Ovarian hyperstimulation syndrome (OHSS) seems to be induced by the ovarian release of vascular endothelial growth factor (VEGF), which increases vascular permeability. Dopamine agonists inhibit VEGF receptor phosphorylation and thereby decrease vascular permeability.Method SA randomized, double-blind, placebo-controlled, multicentre study assessing three oral doses (50, 100, 200 ≥g/day) of the non-ergot derived dopamine agonist quinagolide started on the day of human chorionic gonadotrophin (hCG) and continued for 17-21 days without dose-titration in comparison to placebo in preventing moderate/severe early OHSS (onset ≤9 days after hCG administration) in 182 IVF patients with ≥20 but less than 30 follicles ≥10 mm.Result SThe incidence of moderate/severe early OHSS was 23 (12/53) in the placebo group and 12 (6/51), 13 (7/52) and 4 (1/26) in the quinagolide 50, 100 and 200 g/day groups, respectively. The moderate/severe early OHSS rate was significantly lower with all quinagolide groups combined compared with placebo [P = 0.019; OR = 0.28 (0.09-0.81)]. The incidence of ultrasound evidence of ascites among patients with no clinical pregnancy was significantly reduced from 31 (8/26) with placebo to 11 (8/70) with all quinagolide groups combined [P = 0.033; OR = 0.29 (0.10-0.88)], although there was no difference for those with clinical pregnancy. Quinagolide did not have a detrimental effect on pregnancy or live birth rates. The incidence of gastrointestinal and central nervous system adverse events increased with increasing doses of quinagolide.Conclusion SQuinagolide appears to prevent moderate/severe early OHSS while not affecting treatment outcome. The effect is more marked in patients who did not achieve a clinical pregnancy. Quinagolide administered in high doses without dose-titration is associated with poor tolerability.
Ciray H.N.,University of Leeds |
Campbell A.,CARE Fertility Group |
Agerholm I.E.,Hospitalsenheden Horsens |
Aguilar J.,University of Vigo |
And 3 more authors.
Human Reproduction | Year: 2014
STUDY QUESTION Can the approach to, and terminology for, time-lapse monitoring of preimplantation embryo development be uniformly defined in order to improve the utilization and impact of this novel technology? SUMMARY ANSWER The adoption of the proposed guidelines for defining annotation practice and universal nomenclature would help unify time-lapse monitoring practice, allow validation of published embryo selection algorithms and facilitate progress in this field. WHAT IS KNOWN ALREADY An increasing quantity of publications and communications relating to time-lapse imaging of in vitro embryo development have demonstrated the added clinical value of morphokinetic data for embryo selection. Several articles have identified similar embryo selection or de-selection variables but have termed them differently. An evidence-based consensus document exists for static embryo grading and selection but, to date, no such reference document is available for time-lapse methodology or dynamic embryo grading and selection. STUDY DESIGN, SIZE AND DURATION A series of meetings were held between September 2011 and May 2014 involving time-lapse users from seven different European centres. The group reached consensus on commonly identified and novel time-lapse variables. PARTICIPANTS/MATERIALS, SETTING, METHODS Definitions, calculated variables and additional annotations for the dynamic monitoring of human preimplantation development were all documented. MAIN RESULTS AND THE ROLE OF CHANCE Guidelines are proposed for a standard methodology and terminology for the of use time-lapse monitoring of preimplantation embryo development. LIMITATIONS, REASONS FOR CAUTION The time-lapse variables considered by this group may not be exhaustive. This is a relatively new clinical technology and it is likely that new variables will be introduced in time, requiring revised guidelines. A different group of users from those participating in this process may have yielded subtly different terms or definitions for some of the morphokinetic variables discussed. Due to the technical processes involved in time-lapse monitoring, and acquisition of images at varied intervals through limited focal planes, this technology does not currently allow continuous monitoring such that the entire process of preimplantation embryo development may be visualized. WIDER IMPLICATIONS This is the first time that a group of experienced time-lapse users has systematically evaluated current evidence and theoretical aspects of morphokinetic monitoring to propose guidelines for a standard methodology and terminology of its use and study, and its clinical application in IVF. The adoption of a more uniform approach to the terminology and definitions of morphokinetic variables within this developing field of clinical embryology would allow practitioners to benefit from improved interpretation of data and the sharing of best practice and experience, which could impact positively and more swiftly on patient treatment outcome. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
PubMed | IVI Barcelona, IVI Valencia and Embryotools
Type: Journal Article | Journal: Fertility and sterility | Year: 2016
To evaluate the efficiency of using a continuous (one-step) protocol with a single medium for the culture of human embryos in a time-lapse incubator (TLI).Prospective cohort study on sibling donor oocytes.University-affiliated in vitro fertilization (IVF) center.Embryos from 59 patients.Culture in a TLI in a single medium with or without renewal of the medium on day-3.Embryo morphology and morphokinetic parameters, clinical pregnancy, take-home baby rate, and perinatal outcomes.The blastocyst rates (68.3 vs. 66.8%) and the proportion of good-quality blastocysts (transferred plus frozen) obtained with the two-step (80.0%) protocol were statistically significantly similar to those obtained in the one-step protocol (72.2%). Similarly, morphokinetic events from early cleavage until late blastocyst stages were statistically significantly equivalent between both groups. No differences were found either in clinical pregnancy rates when comparing pure transfers performed with embryos selected from the two-step (75.0%), one-step (70.0%, respectively), and mixed (57.1%) groups. A total of 55 out of 91 embryos transferred implanted successfully (60.4%), resulting in a total of 37 newborns with a comparable birth weight mean among groups.Our findings support the idea that in a TLI with a controlled air purification system, human embryos can be successfully cultured continuously from day 0 onward in single medium with no need to renew it on day-3. This strategy does not affect embryo morphokinetics or development to term and offers more stable culture conditions for embryos as well as practical advantages and reduced costs for the IVF laboratory.