Assessment of embryo implantation potential with a cloud-based automatic software.

RESEARCH QUESTION: Is embryo selection by Dana (automatic software for embryo evaluation) associated with a higher implantation rate in IVF treatments? DESIGN: A three-phase study for Dana system's validation: creation of a data-cloud of known implantation data (KID) embryos from 1676 transferred embryos; embryo evaluation by Dana considering manual annotations and embryo development videos (389 transferred embryos); and validation of Dana automatic selection, without embryologist's intervention (147 transferred embryos); RESULTS: The implantation rate of the 1021 KID embryos from phase 1 served to set four grades of embryos referring to implantation rate: A = 34%, B = 25%, C = 24%, and D = 19%. Phase 2: a classification ranking according to the unit average distance (UAD) and implantation potential was established: top (UAD ≤0.50), high (UAD = 0.51-0.66), medium (UAD = 0.67-1.03) and low (UAD >1.03). Pregnancy rates were 59%, 46%, 36% and 28%, respectively (P < 0.001). Phase 3: embryos were automatically categorized according to Dana's classification ranking. Most implanted embryos were found in groups top, high and medium (UAD ≤1.03), whereas the implantation rate in group low (UAD >1.03) was significantly lower: 46% versus 25%, respectively (P = 0.037). The twin gestation rate was higher when number of top embryos (UAD ≤0.5) transferred were two (52%) versus one (25%) (P < 0.001). CONCLUSIONS: Embryo selection based on Dana ranking increases the success of IVF treatments at least in oocyte donation programmes. The multicentre nature of the study supports its applicability at different clinics, standardizing the embryo development's interpretation. Dana's innovation is that the system increases its accuracy as the database grows.

Selection of preimplantation embryos using time-lapse microscopy in in vitro fertilization: State of the technology and future directions.

In this review, our aim is to give an overview of the state of the technology and clinical outcomes of time-lapse microscopy in improving embryo selection as a key step in in vitro fertilization (IVF). Using traditional incubators, morphologic assessment of the fertilized embryos is limited to snapshots at a few discrete points in time, reducing the amount of information that could potentially be obtained. Time-lapse monitoring overcomes this limitation without exposing the embryos to environmental changes. Moreover, time-lapse may introduce new dynamic markers of embryo competence as well as a versatile embryo evaluation and provides novel information regarding human embryo development. In the last few years, various algorithms have been developed correlating the kinetics of early embryo development to blastocyst formation, implantation potential, chromosomal content and live birth rate. There is not yet a universally accepted algorithm, and significant knowledge gaps remain that can provide opportunities for further research in this field.

The use of morphokinetic as a predictor of implantation.

In recent years the increased efforts intended for improving future outcomes in the laboratory have focused mostly on the search of additional markers of embryo quality to add up present embryo selection criteria. Time-lapse system involves an alternative tool in assisted reproduction techniques, being able to improve the embryo selection from a dynamic and interactive approach while standard embryo assessment implies a subjective and static morphology evaluation and consequently reducing the information gained for embryo selection, time-lapse technology adds several morphokinetic parameters, providing additional input for embryo evaluation. This further information represents a challenge for a potential improvement in implantation rates and reproductive outcomes. This article focuses on the different time-lapse systems burgeoning on the market and the use of morphokinetics as a predictor of embryo implantation.

Obstetric and perinatal outcome of babies born from sperm selected by MACS from a randomized controlled trial.

PURPOSE: The purpose of this study is to assess outcomes after magnetic-activated cell sorting (MACS) technology on obstetric and perinatal outcomes compared with those achieved after swim up from randomized controlled trial. METHODS: This is a two-arm, unicentric, prospective, randomized, and triple-blinded trial and has a total of 237 infertile couples, between October 2010 and January 2013. A total of 65 and 66 newborns from MACS and control group, respectively, were described. RESULTS: MACS had no clinically relevant adverse effects on obstetric and perinatal outcomes. No differences were found for obstetric problems including premature rupture of membranes 6.1% (CI95% 0-12.8) vs. 5.9% (CI95% 0-12.4), 1st trimester bleeding 28.6% (CI95% 15.9-41.2) vs. 23.5% (CI95% 11.9-35.1), invasive procedures as amniocentesis 2.0% (CI95% 0-5.9) vs. 3.9% (CI95% 0-9.2), diabetes 14.3% (CI95% 4.5-24.1) vs. 9.8% (CI95% 1.6-17.9), anemia 6.1% (CI95% 0-12.8) vs. 5.9%(CI95% 0-12.4), 2nd and 3rd trimesters 10.2% (CI95% 1.7-18.7) vs. 5.9% (CI95% 0-12.4), urinary tract infection 8.2% (CI95% 0.5-15.9) vs. 3.9% (CI95% 0-9.2), pregnancy-induced hypertension 6.1% (CI95% 0-12.8) vs. 15.7% (CI95% 5.7-25.7), birth weight (g) 2684.10 (CI95% 2499.48-2868.72) vs. 2676.12 (CI95% 2499.02-2852.21), neonatal height (cm) 48.3 (CI95% 47.1-49.4) vs. 46.5 (CI95% 44.6-48.4), and gestational cholestasis 0%(CI95% 0-0) vs. 3.9% (CI95% 0-9.2), respectively, in MACS group compared with control group. CONCLUSIONS: Our data suggest that MACS technology does not increase or decrease Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation adverse obstetric and perinatal outcomes in children conceived when this technology was performed, being the largest randomized control trial with live birth reported results with MACS.

Automatic time-lapse instrument is superior to single-point morphology observation for selecting viable embryos: retrospective study in oocyte donation.

OBJECTIVE: To correlate the different categories provided by a commercial diagnostic test with blastocyst formation, quality, implantation potential, and ongoing pregnancy (OPR) for the purpose of validating the automatic annotations and the classification algorithm. DESIGN: Observational, retrospective, multicenter cohort study. SETTING: University-affiliated private IVF center. PATIENT(S): A total of 3,002 embryos, including 521 transferred embryos with known implantation, from 626 IVF cycles that were incubated in a conventional incubator and monitored with an automatic time-lapse test. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Embryo selection was based on morphology and the classification provided by a commercial diagnostic test. Implantation was the primary end point, and OPR, blastocyst formation (BR), and embryo morphology were secondary end points. RESULT(S): BR and number of optimal blastocysts were related to the classification test. This correlation was also observed when analyzing implantation rates (day 3 transfer: high 38.2%, medium 31.7% and low 26.1%; day 5 transfer: high 66.7%, medium 50%, low 31%). Patients where no high embryos were transferred (n = 75) had an OPR of 46.70%, and those patients where at least one high embryo was transferred (n = 109) significantly increased OPR to 67%. A logistic regression analysis studying other confounding factors (day of transfer, number of oocytes obtained, and embryo morphology classification) was included. In that model, if at least one of the embryos was labeled as high, OPR was 2.567 times higher than a cycle where no high embryos were transferred. CONCLUSION(S): Our study presents, to our knowledge, the largest set of transferred embryos after time-lapse analysis with the use of an automatic time-lapse test. The provided classification was related to reproductive outcome. Our results suggest that the automated embryo diagnostic test provided extra information to the embryologist to select the best embryos, independently from clinical features of the patient or day of transfer.

New strategy for diagnosing embryo implantation potential by combining proteomics and time-lapse technologies.

OBJECTIVE: To develop a diagnostic tool for embryo implantation potential with the use of proteomic fingerprinting combined with time-lapse morphokinetic analysis. DESIGN: Retrospective cohort study. SETTING: University-affiliated private in vitro fertilization center. PATIENT(S): Seventeen infertile patients undergoing intracytoplasmic sperm injection (ICSI) from our ovum donation program. INTERVENTION(S): No patient intervention. We examined morphokinetic data and proteomic data from the spent media of 16 embryos that implanted and 12 embryos that did not implant. MAIN OUTCOME MEASURE(S): We analyzed seven proteins in the embryo spent media-SCF, TNFR1, PIGF-1, IFN-α2, IL-6, CXCL13, and GM-CSF-with the use of a bead-based multiplexing technology and combined this data with the exact timing (in hours) of cell cycle duration (cc2), blastomere synchrony (s2), and 5-blastomere cleavage (t5) with the use of an incubator equipped with time-lapse videography. RESULT(S): Logistic regression analysis with the use of the forward-step likelihood selection method revealed that the presence/absence of interleukin (IL) 6 and the duration of cc2 were the most relevant embryo features for embryo selection. We combined these two parameters to obtain a hierarchic model that established four categories (A/B/C/D), based on the presence of IL-6 and a cc2 range of 5-12 hours. A direct relationship was observed between the morphologic categories and implantation rates: Those with the presence of IL-6 and 5-12 h cc2 had significantly higher implantation rates. CONCLUSION(S): The strategy we report here combines time-lapse and proteome analysis to improve embryo selection while minimizing handling and monitoring by the embryologist. Our results describe the utility of a combined biochemical/morphokinetic approach to select embryos for transfer according to their implantation potential. Clinical validation with larger sample sizes is mandatory to confirm the effectiveness of this initial study.