Conventional Morphological Assessment Research Articles

O-297 Prediction of pregnancy outcomes of single vitrified-warmed blastocyst transfer using combination of an automatic classification algorithm applied on cleavage stage embryos and blastocyst morphology

Abstract Study question Does combination of embryo assessment algorithm on cleavage-stage based on the automatic annotation of morphokinetic and blastocyst morphology in embryo selection improve implantation outcomes? Summary answer Combination of embryo assessment algorithm on cleavage-stage based on the automatic morphokinetic annotation and blastocyst morphological evaluation was showed significantly predictive for implantation outcomes. What is known already Conventional morphological assessment is still the gold standard for embryo selection. Timelapse monitoring of embryo development may represent a superior way to culture and select embryos in vitro. Nowadays, time-lapse culture systems are becoming more popular, many algorithms have been developed for embryo selection based on embryo morphokinetics, providing additional information for morphological assessment. However, manual annotations of developmental events and application of algorithms can be time-consuming and subjective processes. Automation of morphokinetic annotation can be a potential approach that reduces subjectivity in embryo selection. Study design, size, duration The observational, retrospective study was conducted in a single centre between 2020-2023 and included 511 single vitrified-warmed blastocyst transfer cycles. Blastocyst selected for transfer on Day 5,6 based on conventional morphological evaluation. Embryos were evaluated on Day 3 with a score from 1 (best) to 5 (worst) (from highest to lowest developmental potential) by the automatic embryo assessment algorithm. The correlation of the algorithms scoring and pregnancy outcomes was qualified by generalized estimating equations (GEEs). Participants/materials, setting, methods Embryos were cultured in timelapse GERI incubator and classified on day 3 by automatic embryo assessment algorithm depending on four parameters: P2 (t3-t2), P3 (t4-t3), oocyte age, and number of cells. The correlation of the algorithms scoring and pregnancy outcomes was qualified by generalized estimating equations (GEEs). Three GEE model using embryo assessment algorithm, conventional morphological assessment, and a combination of both classification system as the predictor were compared. Main results and the role of chance The implantation rate was higher with lower the scores generated by the embryo assessment algorithm. A GEE model showed the negative association between higher embryo score and lower odds of implantation. The OR of Score 3; 4; 5 vs 1 were 0.335; 0.259; 0.245 (95% CI 0.194-0.580; 0.138-0.485; 0.111-0.544, P = 0.000), respectively, for implantation. The AUC of the model using embryo assessment algorithm for implantation potential = 0.641. The AUC of the model combining both embryo assessment algorithm and conventional morphological assessment for implantation potential = 0.733. The differences were statistically significant (z-statistic = 3.896, p = 0.0001). Limitations, reasons for caution The sample size was enough to confirm the ability of the model for embryo selection. However, the retrospective nature of this study may be a limitation. Wider implications of the findings Using combination of timelapse technology with automated embryo assessment and conventional morphological assessment can predict the success rates of assisted reproduction cycles. To our knowledge, this is the first study using embryo dataset from single vitrified-warmed blastocyst transfer cycles with this embryo assessment algorithm. Trial registration number not applicable

Assessment of artificial intelligence model and manual morphokinetic annotation system as embryo grading methods for successful live birth prediction: a retrospective monocentric study

PurposeThe introduction of the time-lapse monitoring system (TMS) and the development of predictive algorithms could contribute to the optimal embryos selection for transfer. Therefore, the present study aims at investigating the efficiency of KIDScore and iDAScore systems for blastocyst stage embryos in predicting live birth events.MethodsThe present retrospective study was conducted in a private IVF Unit setting throughout a 10-month period from October 2021 to July 2022, and included the analysis of 429 embryos deriving from 91 IVF/ICSI cycles conducted due to infertility of various etiologies. Embryos incubated at the Embryoscope+ timelapse incubator were analyzed through the established scoring systems: KIDScore and iDAScore®. The main outcome measure was the comparison of the two scoring systems in terms of live birth prediction. Embryos with the higher scores at day 5 (KID5 score/iDA5 score) were transferred or cryopreserved for later use.ResultsEmbryos with high KID5 and iDA5 scores positively correlated with the probability of successful live birth, with KID5 score yielding a higher efficiency in predicting a successful reproductive outcome compared to a proportionally high iDA5 score. KID5 demonstrated conservative performance in successfully predicting live birth compared to iDA5 score, indicating that an efficient prediction can be either provided by a relatively lower KID5 score or a relatively higher iDA5 score.ConclusionThe developed artificial intelligence tools should be implemented in clinical practice in conjunction with the conventional morphological assessment for the conduction of optimized embryo transfer in terms of a successful live birth.

P-111 External validation of a model for prioritizing day 3 embryos for transfer based on deep learning and time-lapse images

Abstract Study question Could an objective embryo assessment by iDAScore version 2.0 perform as well as a conventional morphological assessment according to the Istanbul consensus report? Summary answer iDAScore version 2.0 performed as well or even better than conventional embryo assessment in fresh day 3 embryo transfer cycles. What is known already The pregnancy prediction performance of iDAScore version 1.0 has been confirmed in a large cohort study with vitrified-warmed blastocyst transfer, the validation results showed that it performs as well or better than conventional embryo evaluation. iDAScore version 2.0 was developed for transfers on both day 2, day 3 and day 5 transfers, however, the performance of iDAScore version 2.0 has not been verified with independent datasets. Study design, size, duration A single-center large cohort retrospective study from an independent validation test was carried out, including 4328 cleavage embryo transfers cycles performed between January 2020 and June 2022. Participants/materials, setting, methods The selection of embryos for transfer was based on conventional morphological assessment model according to Istanbul consensus report, and the transferred embryos were retrospectively evaluated by the iDAScore version 2.0 model. The pregnancy prediction performances of the two day 3 embryo assessment models were compared using the area under curve (AUC) for predicting the FHB for all cycles and subgroup analysis(SET and DET; female age <35 and ≥ 35 year; number of blastomeres <8c and ≥8c). Main results and the role of chance The FHB rate in the iDAScore (2.0-3.9) group was lower than in all iDAScore group, iDAScore (4.0-5.9), and (6.0-8.0) groups within the poor, fair and good group. Additionally, for fair and good group, the FHB rate in iDAScore (6.0-8.0) group was higher than that in other iDAScore groups. The AUCs of iDAScore were significantly greater than the conventional morphology assessment, for all cycles (0.62 vs. 0.59, P < 0.05), SET cycles (0.63 vs. 0.59, P < 0.05) and DET cycles (0.61 vs. 0.59, P < 0.05). For the sub-groups of age, the AUC of iDAScore was significantly greater than the conventional morphology assessment in < 35 group (0.62 vs. 0.59, P < 0.05). However, there was no significant difference between the two assessment model in ≥ 35 group (0.60 vs. 0.58, P > 0.05). For the sub-groups of the number of blastomeres, a significantly greater AUC was observed for iDAScore than for conventional morphology assessment, for both the <8c group (0.67 vs. 0.56, P < 0.05) and the ≥ 8c group (0.58 vs. 0.55, P < 0.05). Limitations, reasons for caution the limitation of the findings is that all analyzed embryos were selected previously by morphology. Although the conventional morphological assessment is a widely used morphological grading system, it is subjective and susceptible to inter-observer variation. Wider implications of the findings iDAScore version 2.0 may be a promising tool for selecting day 3 embryos with the highest likelihood of implantation. A fully automated evaluation system also significantly reduced the time used for embryo selection and eliminates subjectivity. Trial registration number none

External validation of a model for selecting day 3 embryos for transfer based upon deep learning and time-lapse imaging

Could objective embryo assessment using iDAScore Version 2.0 perform as well as conventional morphological assessment? A retrospective cohort study of fresh day 3 embryo transfer cycles was conducted at a large reproductive medicine centre. In total, 7786 embryos from 4328 cycles with known implantation data were cultured in a time-lapse incubator and included in the study. Fetal heartbeat (FHB) rate was analysed retrospectively using iDAScore Version 2.0 and conventional morphological assessment associated with the transferred embryos. The pregnancy-prediction performance of the two assessment methods was compared using area under the curve (AUC) values for predicting FHB. AUC values were significantly higher for iDAScore compared with morphological assessment for all cycles (0.62 versus 0.60; P = 0.005), single-embryo transfer cycles (0.63 versus 0.60; P = 0.043) and double-embryo transfer cycles (0.61 versus 0.59; P = 0.012). For the age subgroups, AUC values were significantly higher for iDAScore compared with morphological assessment in the <35 years subgroup (0.62 versus 0.60; P = 0.009); however, no significant difference was found in the ≥35 years subgroup. In terms of the number of blastomeres, AUC values were significantly higher for iDAScore compared with morphological assessment for both the <8c subgroup (0.67 versus 0.56; P < 0.001) and the ≥8c subgroup (0.58 versus 0.55; P = 0.012). iDAScore Version 2.0 performed as well as, or better than, conventional morphological assessment in fresh day 3 embryo transfer cycles. iDAScore Version 2.0 may therefore constitute a promising tool for selecting embryos with the highest likelihood of implantation.

O-165 Impact of endometriosis on the oocyte

Abstract Available evidence indicates that women with endometriosis tend to have lower implantation rates following IVF than those without endometriosis. Whether this reduction in implantation rate is due to compromised endometrial receptivity or reduced embryo quality remains controversial. However, studies with the oocyte donor model in which reciprocal transfers are performed involving oocytes/embryos from women with or without endometriosis support the conclusion that oocyte quality is the main factor compromising implantation rate. This conclusion is consistent with documented elevations of inflammatory cytokines, reactive oxygen species and growth- and angiogenic factors in follicular fluid and peritoneal fluid of women diagnosed with endometriosis. In this lecture, we will review evidence in support of negative effects of endometriosis on oocyte quality. We will discuss the results of studies directly assessing oocyte quality through gross morphological analyses and transmission electron microscopy assessments on human oocytes. Given the paucity of human oocytes available for research, we will then consider studies on animal oocytes matured in vitro in medium supplemented with either follicular fluid or peritoneal fluid from women with endometriosis. We will then proceed to reviewing the clinical IVF literature assessing the relationship between endometriosis and embryo quality, as the latter is predominantly driven by oocyte quality. We will specifically appraise studies investigating any association between endometriosis and 1) the proportion of good quality embryos and blastocyst formation rate, as categorized by conventional morphology assessment; and 2) risks of aneuploidy, and aberrations in embryo morphokinetics identified by time-lapse imaging. We will close by a brief discussion of the challenges that prevail in untangling negative effects of endometriosis on oocyte quality.

Noninvasive embryo evaluation and selection by time-lapse monitoring vs. conventional morphologic assessment in women undergoing in vitro fertilization/intracytoplasmic sperm injection: a single-center randomized controlled study

To determine whether time-lapse monitoring (TLM) for cleavage-stage embryo selection improves reproductive outcomes in comparison with conventional morphological assessment (CMA) selection. Prospective randomized controlled trial. Single academic center. We randomly assigned 139 women who were undergoing their first invitro fertilization or intracytoplasmic sperm injection cycle to undergo either fresh embryo transfer or first frozen embryo transfer (FET). Only 1 cleavage-stage embryo was transferred to each participant. The patients were randomly assigned to either the CMA or the TLM group. In the CMA group, day 2 and day 3 embryos were observed. A good-quality cleavage-stage embryo was selected for transfer or freezing in both groups. The primary and secondary outcomes were the clinical pregnancy rate (CPR) and the live birth rate (LBR), respectively, after the first embryo transfer (fresh embryo transfer or FET). The CPR and LBR were significantly lower in the TLM group than in the CMA group (CPR: 49.18% vs. 70.42%; relative risk, 0.70; 95% confidence interval [CI], 0.52-0.94; LBR: 45.90% vs. 64.79%; relative risk, 0.71; 95% CI, 0.51-0.98). The CPR with fresh embryo transfer or FET did not significantly differ between the TLM and the CMA groups (fresh embryo transfer: 44.44% vs. 70.0%, relative risk, 0.63, 95% CI, 0.39-1.03; FET: 52.94% vs. 70.73%, relative risk, 0.75, 95% CI, 0.52-1.09). There was a significant difference in the LBR with fresh embryo transfer between the TLM and the CMA groups (40.74% vs. 66.67%; relative risk, 0.61; 95% CI, 0.36-1.03). The LBRs with FET were similar in the TLM and the CMA groups (50.0% vs. 63.41%; relative risk, 0.79; 95% CI, 0.52-1.19). The rates of early spontaneous abortion and ectopic pregnancy did not differ between the TLM and the CMA groups. Elective single cleavage-stage embryo transfer with TLM-based selection did not have any advantages over CMA when day 2 and day 3 embryo morphology was combined in young women with a good ovarian reserve. Because of these results, we conclude that TLM remains an investigational procedure for invitro fertilization practice. ChiCTR1900021981.

Oocyte quality and embryo selection strategies: a review for the embryologists, by the embryologists.

With the advance of assisted reproduction techniques, and the trend towards blastocyst culture and single embryo transfer, gamete and embryo assessment have gained greater importance in ART treatment. Embryo quality depends mainly on gamete quality and culture conditions. Oocyte maturity identification is necessary in order to plan fertilization timing. Mature oocytes at the metaphase II stage show a higher fertilization rate compared to immature oocytes. Morphology assessment is a critical yet challenging task that may serve as a good prognostic tool for future development and implantation potential if done effectively. Various grading systems have been suggested to assess embryos at pronuclear, cleavage, and blastocyst stages. By identifying the embryo with the highest implantation potential, it is possible to reduce the number of embryos transferred without compromising the chances of a successful pregnancy. Apart from the conventional morphology assessment, there are several invasive or non-invasive methods for embryo selection such as preimplantation genetic testing, morphokinetics, proteomics, metabolomics, oxygen consumption, and measurement of oxidative stress in culture medium. Morphokinetics is a method based on time-lapse technology and continuous monitoring of embryos. In this review, we aimed to describe and compare the most effective and widely used methods for gamete and embryo assessment as well as embryo selection.

O-208 High sperm DNA fragmentation index negatively impacts embryo morphokinetics, but not embryo morphology and development rates: the importance of time-lapse imaging system

Abstract Study question Can time-lapse imaging (TLI) identify morphokinetic events impacted by high sperm DNA fragmentation index (DFI), irrespective of conventional morphological embryo assessment and development rate? Summary answer Embryo morphokinetic parameters are negatively impacted by high DFI, whereas conventional morphological embryo assessment and blastocyst development rate are not related to DNA integrity. What is known already Paternal genome activation occurs late in the embryo, and therefore, the negative impact of sperm factors on embryo development is more often observed in the outcomes of pregnancy, such as embryonic implantation and pregnancy loss, than in the potential for embryonic development itself, such as successful development to the blastocyst stage. With the development of TLI technology, and the possibility of assessing complete embryonic development, we hypothesized that sperm factors related to DNA fragmentation may interfere with the speed and pattern of cell divisions, leading to slower embryos; something that would not be detected by conventional morphological embryo assessment. Study design, size, duration The study included 978 zygotes cultured until day five in a TLS incubator between March/2019 and August/2020, derived from 118 patients undergoing ICSI in a private university-affiliated IVF center. Kinetic markers from the point of insemination were recorded. Generalized linear models adjusted for potential confounders, followed by Bonferroni post hoc were used to compare timing of specific events in patients with low (&amp;lt;30%) of high (≥30%) DFI. The post hoc achieved power was &amp;gt; 90%. Participants/materials, setting, methods Recorded kinetic markers were: timing to pronuclei appearance and fading (tPNa and tPNf), timing to two (t2), three (t3), four (t4), five (t5), six (t6), seven (t7), and eight cells (t8), and timing to morulae (tM), start of blastulation (tSB) and blastulation (tB). Durations of second and third cell cycles (cc2 and cc3) and timing to complete synchronous divisions s1, s2, and s3 were calculated. The KIDScore ranking was also recorded. Main results and the role of chance Blastocyst development (53.1% ± 1.3 vs. 55.1% ± 1.5, p = 0.380) and high-quality rates (87.9% ± 2.9 vs. 86.2% ± 3.6, p = 0.749) were similar between embryos derived from sperm samples with &amp;lt;30% DFI (n = 592) and ≥30% DFI (n = 386), respectively. Embryos derived from sperm samples with ≥30% DFI showed significantly slower divisions compared to those from &amp;lt;30% DFI: tPNa (6.1h ± 0.2 vs. 6.8h ± 0.2, p = 0.030), tPNf (23.0h ± 0.3 vs. 24.2h ± 0.3, p = 0.009), t2 (25.4h ± 0.3 vs. 26.9h ± 0.3, p = 0.002), t3 (34.8h ± 0.3 vs. 37.3h ± 0.4, p &amp;gt; 0.001), t4 (37.5h ± 0.4 vs. 39.3h ± 0.4, p = 0.003), t5 (46.2h ± 0.5 vs. 49.5h ± 0.6, p &amp;lt; 0.001), t6 (49.7h ± 0.5 vs. 52.8h ± 0.6, p = 0.001), t7 (52.4h ± 0.6 vs. 55.6h ± 0.7, p = 0.001), t8 (56.2h ± 0.7 vs. 58.9h ± 0.8, p = 0.017), tSB (97.5h ± 1.5 vs. 105.9h ± 1.7, p = 0.002), tB (108.6h ± 0.8 vs. 112.4h ± 1.2, p = 0.016). The KIDScore ranked significantly different between embryos derived from samples with &amp;lt;30% or ≥ 30% DFI (4.5 ± 0.1 vs. 3.9 ± 0.2, p = 0.033, respectively). A significant difference was observed in implantation rate (&amp;lt;30% DFI: 51.5% ± 2.2 vs. ≥30% DFI: 30.5% ± 1.3, p &amp;lt; 0.001). Limitations, reasons for caution Retrospective nature of this study and the small sample size may be a reason for caution, despite adequate power has been achieved. Wider implications of the findings Increasing DFI correlates with delayed cell cleavage and blastulation, leading to reduced implantation rates, without compromising blastulation rate and quality. This finding highlights the importance of TLI for the identification and de-selection of slow-growing embryos for transfer, in cycles with high DFI. Trial registration number Not applicable

P–241 Construction of a Machine Learning algorithm based on early morphokinetics for human blastocyst development prediction: a retrospective analysis of 575 cleavage-stage embryos

Abstract Study question Can morphokinetic features included into Machine Learning (ML) algorithms identify cleavage-stage embryos with the best chance to reach the expanded blastocyst stage on day 5? Summary answer A ML algorithm based on early morphokinetic features can identify cleaving embryos that will reach the expanded blastocyst stage on day 5. What is known already To date, the conventional morphology assessment of cleaving human embryos has a limited predictive power on further embryo developmental potential. The morphokinetic analysis using Time-Lapse systems (TLS) was introduced in order to provide a new tool to identify dynamic biomarkers of embryo quality. More recently, ML approach has been applied for the analysis of specific embryo-related features, aiming at developing predictive algorithms to assess the embryo development potential. Study design, size, duration We retrospectively analysed 575 embryos obtained from 80 women aged 25–42 years, with normal BMI, AFC≥8, day 3 FSH&amp;lt;12 IU/l, AMH&amp;gt;2.5 ng/ml, no diagnosis of polycystic ovary syndrome or endometriosis. These patients underwent IVF at our IVF Unit between March 2018 and March 2020; their embryos were cultured using the Geri plus® TLS and a single blastocyst transfer was performed. Participants/materials, setting, methods A total number of 29 morphological and morphokinetic parameters were considered to build six different ML algorithms. The performance to assess which was the best-fitting algorithm was calculated using the ROC curve considering accuracy (% of embryos correctly classified by the algorithm), Cohen-kappa coefficient (measurement of the agreement among features), mean number of TP (embryos correctly classified as undergoing developmental arrest), mean number of TN (embryos uncorrectly classified as undergoing developmental arrest). Main results and the role of chance Overall, 210 embryos progressed to the expanded blastocyst stage on day 5 (BL group), whereas 365 displayed developmental delay or arrest at any stage (nBL group). Among the six different algorithms, the best-fitting algorithm was obtained using the Kbest features selection approach combined with a Random Forrest evaluation strategy. This algorithm was based on 7 variables: embryo morphological score on day 2, pronuclear fading time (tPNf), completion time of cleavage to two, four and eight cells (t2, t4, and t8 respectively), time intervals t4-t3 and t8-t4. The algorithm showed an AUC of 0.78, with an accuracy of 0.73, a Cohen-kappa of 0.41, a mean TP number of 302/365 embryos in the nBL group and a mean TN number of 120/210 embryos in the BL group. Mean false positive (FP) and false negative (FN) numbers were of 63 and 90.2, respectively. Limitations, reasons for caution The results obtained in this study may not be generalizable to patients with other clinical characteristics, to other time-lapse systems or different laboratory settings. The predictive power of the algorithm should be validated prospectively on a larger number of embryos. Wider implications of the findings: The current study represents a preliminary analysis for the development of hierarchical predictive models for embryo assessment based on their developmental potential, that embryologists will be able to apply as a support for decision-making. Trial registration number Not applicable

Review of computer vision application in in vitro fertilization: the application of deep learning-based computer vision technology in the world of IVF.

In vitro fertilization has been regarded as a forefront solution in treating infertility for over four decades, yet its effectiveness has remained relatively low. This could be attributed to the lack of advancements for the method of observing and selecting the most viable embryos for implantation. The conventional morphological assessment of embryos exhibits inevitable drawbacks which include time- and effort-consuming, and imminent risks of bias associated with subjective assessments performed by individual embryologists. A combination of these disadvantages, undeterred by the introduction of the time-lapse incubator technology, has been considered as a prominent contributor to the less preferable success rate of IVF cycles. Nonetheless, a recent surge of AI-based solutions for tasks automation in IVF has been observed. An AI-powered assistant could improve the efficiency of performing certain tasks in addition to offering accurate algorithms that behave as baselines to minimize the subjectivity of the decision-making process. Through a comprehensive review, we have discovered multiple approaches of implementing deep learning technology, each with varying degrees of success, for constructing the automated systems in IVF which could evaluate and even annotate the developmental stages of an embryo.

Morphological and genetic heterogeneity of synchronous multifocal lung adenocarcinoma in a Chinese cohort

BackgroundSynchronous multifocal lung cancer (SMLC) is diagnosed with increasing frequency in clinical practice globally. Due to innate variation in clinical management and outcome, it is vital to properly distinguish between synchronous multifocal primary lung cancer (SMPLC) and intrapulmonary metastasis (IM). The pathologic features and principal classification criteria of multifocal lung cancer remain unclear. Our objective was to evaluate the diagnostic value of histological morphologic features and driver gene mutations in SMLC classification.MethodsWe collected a unique cohort of Chinese patients with SMLC, and fully explored the morphologic, immunohistochemical, and molecular features of the disease. Twenty-one SMLC patients with a total of 50 tumours were included in our study. The pathological features that were presented by these patients were analysed, including the tumours location, tumours size, pathological types, predominant pattern of adenocarcinoma, and immunohistochemical staining. We conducted molecular testing of nine driver oncogenes that are associated with lung cancer, namely, EGER, KRAS, BRAF, NRAS, ALK, ROS1, RET, HER2, and PIK3CA.ResultsAccording to the Martini-Melamed classification and refined standard, 8 and 17 patients, respectively, were considered to have SMPLCs. Gene mutations were identified in 18 tumours (36%). Twelve patients had different gene mutations.ConclusionsWe demonstrate that conventional morphological assessment is not sufficient to clearly establish the clonal relationship of SMPLCs. Instead, the evaluation of histological subtypes, including nonmucinous adherent components, is required. Multiplex genotypic analysis may also prove to be a useful additional tool.

Mitral valve repair based on intraoperative objective parameters measurement: State of the art and perspective

Currently, mitral valve repair (MVr) success for primary mitral regurgitation relies mainly on surgeon's expertise and major heterogeneities are observe concerning MVr rate, technics, and results. MVr success is estimated by a morphological echocardiographic assessment after aortic unclamping. To date, coaptation forces have been poorly characterized. We developed a device allowing a precise morphologic and qualitative assessment of coaptation. A first prototype allowing three-dimensional mapping of coaptation forces was developed and a provisional patent was filed. A number of features informed the design of the new device, including force sensitivity, flexibility, and biocompatibility. Varying sensing technologies were screened (including piezo-electric, piezo-resistive, and resistive sensors), and a specific device to hold the sensor was designed and prototyped. The first generation of prototype was tested on a porcine ex vivo beating heart model. The device was inserted between the mitral leaflet through a left atrial incision between two running sutures. The sensor was positioned and connected to a custom-made acquisition system. The coaptation signal was recorded in normal valves and after creation of a posterior central prolapse. We were able to obtain precise surface mapping of mitral coaptation forces in this model. The coaptation signal was notably more intense in the normal valve compare to the prolapsed valve in otherwise similar hemodynamic conditions ( Fig. 1 ). A mapping of coaptation forces along the entire mitral valve surface can be achieved with the method and device we have developed. This technology may be useful to assist surgeons during MVr while providing real-time objective measurement in support of the conventional intraoperative morphological assessment. An extensive development roadmap has been developed and is being put in place to move our invention toward clinical trials.

Evolution of embryo selection for IVF from subjective morphology assessment to objective time-lapse algorithms improves chance of live birth.

Does using an objective time-lapse imaging algorithm (TLIA) after IVF relate to conventional morphological assessment of human blastocysts as a prognosticator for live birth? Prospective use of a TLIA to select embryos in multicentre IVF clinics all using the same strictly controlled laboratory protocols. Each blastocyst was given a ranking from A to D, with the highest rank preferred for fresh transfer. This ranking was retrospectively compared with a given morphological score, which was blinded to the TLIA rank; all embryos were cultured under the same conditions. Using multiple variable logistic regression models, TLIA embryo rank enabled greater discrimination between cycles with and without live births than the conventional morphology grade, even when considered in isolation, and when adjusting for covariates related to treatment and patient criteria. Of the 1810 cycles of single blastocyst transfer, 894 (49.4%) resulted in a live birth. A Vuong non-nested test including covariates showed strong evidence of the superiority of the embryo rank model compared with the transfer grade model (P=0.0008 [raw], P=0.0003 [Akaike information criterion - corrected]). From the receiver operating characteristic (ROC) curves across all possible thresholds the TLIA rank showed better true positive and true negative rates and had a higher area under the curve [AUC] of 67.43% compared with 61.74% for the blastocyst morphology grade. The same analysis but excluding covariates demonstrated an AUC of 62.86% versus 54.02%, respectively. Objective TLIA is superior for selecting embryos for their propensity to generate a live birth over a conventional, subjective blastocyst morphology scoring system.

Time-lapse systems for embryo incubation and assessment in assisted reproduction.

Time-lapse systems for embryo incubation and assessment in assisted reproduction.

Altered morphokinetics in equine embryos from oocytes exposed to DEHP during IVM.

Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer with endocrine-disrupting properties. In this study, we used an equine model to investigate DEHP concentrations in ovarian follicular fluid (FF), and to determine the effects of exposure of oocytes to potentially toxic concentrations of DEHP during in vitro maturation (IVM) on embryo development and quality. Embryo development was evaluated using time-lapse monitoring (TLM), a photomicroscopic tool that reveals abnormalities in cleavage kinetics unobservable by conventional morphology assessment. Blastocyst bioenergetic/oxidative status was assessed by confocal analysis. The possibility that verbascoside (VB), a bioactive polyphenol with antioxidant activity, could counteract DEHP-induced oocyte oxidative damage, was investigated. DEHP was detected in FF and in IVM media at concentrations up to 60 nM. Culture of oocytes in the presence of 500 nM DEHP delayed second polar body extrusion, reduced duration of the second cell cycle, and increased the percentage of embryos showing abrupt multiple cleavage, compared with controls. Mitochondrial activity and intracellular levels of reactive oxygen species were reduced in blastocysts from DEHP-exposed oocytes. VB addition during IVM limited DEHP-induced blastocyst damage. In conclusion, DEHP is detectable in equine FF and culture medium, and oocyte exposure to increased concentrations of DEHP during IVM affects preimplantation embryo development. Moreover, TLM, reported for the first time in the horse in this study, is an efficient tool for identifying altered morphokinetic parameters and cleavage abnormalities associated with exposure to toxic compounds.

The relationship between the conventional blastocyst morphological assessment and karyotyping

The relationship between the conventional blastocyst morphological assessment and karyotyping

Euploid embryos selected by an automated time-lapse system have superior SET outcomes than selected solely by conventional morphology assessment.

We investigated if automated TLI selection may be a valuable strategy to identify those euploid embryos with the best chances of success. This is a unicentric and retrospective study involving 244 patients undergoing preimplantational genetic screening (PGS) cycles with autologous oocytes or oocyte donation (OD) with single euploid embryo transferred. We examined euploid embryos selected for transfer based on morphology evaluation alone (PGS-only; control group) or by assessment using an automated TLI system (Eeva™; PGS-TLI group). In both, autologous oocytes and OD patients, significantly better implantation and clinical and ongoing pregnancy rates were obtained in the PGS-TLI group when euploid embryos with high implantation potential as predicted by the automated TLI System (Eeva™) were transferred compared with the PGS-only group. This improvement was also observed when only transfers of good morphological quality embryos were compared. TLI categories showed significant differences on blastocyst formation and euploidy rate. Automated TLI combined with PGS is a useful prognostic tool to identify euploid embryos with the highest potential for implantation and pregnancy. Further, these results provide evidence that a healthy pregnancy does not only depend upon normal chromosomal status.

Time-lapse imaging algorithms rank human preimplantation embryos according to the probability of live birth.

Can blastocysts leading to live births be ranked according to morphokinetic-based algorithms? Retrospective analysis of 781 single blastocyst embryo transfers, including all patient clinical factors that might be potential confounders for the primary outcome measure of live birth, was weighed using separate multi-variable logistic regression models. There was strong evidence of effect of embryo rank on odds of live birth. Embryos were classified A, B, C or D according to calculated variables; time to start (tSB) and duration (dB{tB - tSB}) of blastulation. Embryos of rank D were less likely to result in live birth than embryos of rank A (odds ratio [OR] 0.3046; 95% confidence interval [CI] 0.129, 0.660; P<0.005). Embryos ranked B were less likely to result in live birth than those ranked A (OR 0.7114; 95% Cl 0.505, 1.001; P<0.01), and embryos ranked C were less likely to result in live birth than those ranked A (OR 0.6501, 95% Cl 0.373, 1.118; P<0.01). Overall, the LRT (Likelihood Ratio Test) p-value for embryo rank shows that there is strong evidence that embryo rank is informative as a whole in discriminating between live birth and no live birth outcomes (p= 0.0101). The incidence of live birth was 52.5% from rank A, 39.2% from rank B, 31.4% from rank C and 13.2% from rank D. Time-lapse imaging morphokinetic-based algorithms for blastocysts can provide objective hierarchical ranking of embryos for predicting live birth and may have greater discriminating power than conventional blastocyst morphology assessment.

Time-lapse systems for embryo incubation and assessment in assisted reproduction.

Background Embryo incubation and assessment is a vital step in assisted reproductive technology (ART). Traditionally, embryo assessment has been achieved by removing embryos from a conventional incubator daily for assessment of quality by an embryologist, under a light microscope. Over recent years time-lapse systems (TLSs) have been developed which can take digital images of embryos at frequent time intervals. This allows embryologists, with or without the assistance of computer algorithms, to assess the quality of the embryos without physically removing them from the incubator. The potential advantages of a TLS include the ability to maintain a stable culture environment, therefore limiting the exposure of embryos to changes in gas composition, temperature and movement. Additionally a TLS has the potential advantage of improving embryo selection for ART treatment by utilising additional information gained through monitoring embryo development. Objectives To determine the effect of a TLS compared to conventional embryo incubation and assessment on clinical outcomes in couples undergoing ART. Search methods A comprehensive search of all the major electronic databases, including grey literature, was undertaken in co-ordination with the Trials Search Co-ordinator of the Cochrane Menstrual Disorders and Subfertility Group in July 2014 and repeated in November 2014 to confirm that the review is up to date. Selection criteria Two authors (SA and NA) independently scanned the titles and abstracts of the articles retrieved by the search. Full texts of potentially eligible randomised controlled trials (RCTs) were obtained and examined independently by the authors for their suitability according to the review inclusion criteria. In the case of doubt between the two authors, a third author (LC) was consulted to gain consensus. The selection process is documented with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart. Data collection and analysis Data were obtained and extracted by two authors. Disagreement was resolved by consensus. Trial authors were contacted by e-mail to obtain further study information and data. All extracted data were dichotomous outcomes and odds ratios (OR) were calculated on an intention-to-treat basis. Where enough data were available, meta-analysis was undertaken. Main results Three studies involving 994 women were found for inclusion. Data from all three studies were used to address comparison one, TLS with or without cell-tracking algorithms versus conventional incubation. No studies were found to address comparison two, TLS utilising cell-tracking algorithms versus TLS not utilising cell-tracking algorithms. There was only one study which reported live birth (n = 76). The results demonstrated no conclusive evidence of a difference in live birth rate per couple randomly assigned to the TLS and conventional incubation arms of the study (OR 1.1, 95% CI 0.45 to 2.73, 1 RCT, n = 76, moderate quality evidence). All three studies reported miscarriage (n = 994). There was no conclusive evidence of a difference in miscarriage rates per couple randomly assigned to the TLS and conventional incubation arms (OR 0.70, 95% CI 0.47 to 1.04, 3 RCTs, n = 994, I2 = 0%, low quality evidence). Only one study reported stillbirth rates (n = 76). There were equal numbers of stillbirths in both the TLS and conventional incubation arms of the study. Therefore, there was no evidence of a difference in the stillbirth rate per couple randomly assigned to TLS and conventional incubation (OR 1.0, 95% CI 0.13 to 7.49, 1 RCT, moderate quality evidence). All three studies reported clinical pregnancy rates (n = 994). There was no conclusive evidence of a difference in clinical pregnancy rate per couple randomly assigned to the TLS and conventional incubation arms (OR 1.23, 95% CI 0.96 to 1.59, 3 RCTs, n = 994, I2 = 0%, low quality evidence). None of the included studies reported cumulative clinical pregnancy rates. Authors' conclusions There is insufficient evidence of differences in live birth, miscarriage, stillbirth or clinical pregnancy to choose between TLS and conventional incubation. Further data explicitly comparing the incubation environment, the algorithm for embryo selection, or both, are required before recommendations for a change of routine practice can be justified.

Correspondence between retinotopic cortical mapping and conventional functional and morphological assessment of retinal disease

PurposeThe present study describes retinotopic mapping of the primary visual cortex using functional MRI (fMRI) in patients with retinal disease. It addresses the relationship between fMRI data and data obtained...