External validation of a time-lapse model; a retrospective study comparing embryo
            evaluation using a morphokinetic model to standard morphology with live birth as
            endpoint

Adolfsson, Emma; Porath, Sandra; Andershed, Anna Nowosad

doi:10.5935/1518-0557.20180041

Cited by 19 publications

(23 citation statements)

References 37 publications

(46 reference statements)

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“…Several authors have indicated that morphokinetic parameters are characteristic of blastocyst formation (Wong et al , 2010; Conaghan et al , 2013; Milewski et al , 2015; Motato et al , 2016) and pregnancy or implantation (Meseguer et al , 2011; VerMilyea et al , 2014; Basile et al , 2015; Liu et al , 2016; Milewski et al , 2016; Motato et al , 2016; Petersen et al , 2016; Carrasco et al , 2017) but the general applicability of former morphokinetic algorithms for pregnancy, implantation or birth prediction is currently subject to controversy. Some authors who were not involved in developing the algorithms have maintained that time-lapse algorithms have a significantly higher predictive power than conventional scoring (Adamson, 2016; Kieslinger et al , 2016; Adolfsson et al , 2018; Liu et al , 2018), while other authors were unable to show a significant predictive capability for pregnancy, implantation or live birth (Kirkegaard et al , 2014; Yalçınkaya et al , 2014; Fréour et al , 2015; Ahlstrom et al , 2016; Goodman et al , 2016; Barrie et al , 2017; Adolfsson et al , 2018). These discrepancies are probably due to the fact that timing is markedly influenced by the fertilisation method (Lemmen et al , 2008), culture medium (Ciray et al , 2012), oxygen level (Kirkegaard et al , 2013a), population features (Fréour et al , 2013; Wissing et al , 2014) and controlled stimulation protocols.…”

Section: Discussionmentioning

confidence: 99%

Can novel early non-invasive biomarkers of embryo quality be identified with time-lapse imaging to predict live birth?

et al. 2019

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STUDY QUESTION Can time-lapse imaging systems make it possible to identify novel early non-invasive biomarkers to predict live birth? SUMMARY ANSWER From mostly high-grade embryos, out of 35 morphometric, morphologic and morphokinetic variables, only pronuclei (PN) position at time of PN juxtaposition and the absence of multinucleated blastomeres at the 2-cell stage (MNB2cell), were potentially associated with live birth. WHAT IS KNOWN ALREADY Previous studies indicate that some kinetic markers may be predictive of blastocyst development and embryonic implantation. Certain teams have suggested including some of them in decisional algorithms for embryo transfers. STUDY DESIGN, SIZE, DURATION Using a time-lapse incubator (EmbryoScope, Unisense FertiliTech), we retrospectively explored the associations between the morphometric, morphologic and morphokinetic parameters of oocytes, zygotes and embryos, and their associations with live birth. This study assessed 232 embryos from single embryo transfers after ICSI cycles performed between January 2014 and December 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS The morphometric, morphologic and morphokinetic parameters (18, 4 and 13, respectively) of oocytes, zygotes and early embryos were studied retrospectively. The associations between these parameters were examined using a Spearman’s correlation, Mann–Whitney or chi-squared test as appropriate. We examined whether these parameters were associated with outcomes in univariate and multivariate logistic regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE Central PN juxtaposition was associated with a 2-fold increase in the odds of live birth (OR = 2.20; 95% CI, [1.26–3.89]; P = 0.006), while the presence of MNB2cell was associated with half the odds of live birth (OR = 0.51; 95% CI, [0.27–0.95]; P = 0.035). These two parameters were independent of embryo kinetics. The 33 remaining parameters had no significant association with the capacity of transferred embryos to develop to term. LIMITATIONS, REASONS FOR CAUTION Even though the population size was relatively small, our analyses were based on homogeneous cycles, i.e. young women whose transferred embryos were found to be high-grade according to conventional morphology evaluation. In addition, our conclusions were established from a specific, highly selected population, so other study populations, such as women in an older age bracket, may yield different results. Finally, because we assessed day 2/3 transfers, our findings cannot be generalized to embryos cultured up to the blastocyst stage. WIDER IMPLICATIONS OF THE FINDINGS It would be interesting to explore, prospectively, whether PN localisation is a relevant measure to predict embryo development when added into further algorithms and whether this parameter could be suitable for use in other IVF clinics. Further studies are needed, notably to explore the added value of timing evaluation in cohorts of embryos with low or intermediate morphology grade, as well as in other maternal populations (i.e. older women). STUDY FUNDING/COMPETING INTEREST(S) No external funding was used for this study. P. Sagot received funding from the following commercial companies: Merck Serono, Finox Biotech, Ferring, MSD France SAS, Teva Sante ́ SAS, Allergan France, Gedeon Richter France, Effik S.A., Karl Storz Endoscopie France, GE Medical Systems SCS, Laboratoires Genevrier, H.A.C. Pharma and Ipsen. All the authors confirm that none of this funding was used to support the research in this study. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the journal policies on sharing data and materials.

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Section: Discussionmentioning

confidence: 99%

Can novel early non-invasive biomarkers of embryo quality be identified with time-lapse imaging to predict live birth?

et al. 2019

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“…The ongoing pregnancy rate was relatively high (57.2% vs. 60.1%, p = 0.71). Recently, the predictive value of morphokinetic parameters has been studied 13,26,[38][39][40][41][42] . Our study was a retrospective cohort study which was compiled data from July 2014 to July 2017.…”

Section: Discussionmentioning

confidence: 99%

Comparison of clinical outcome of frozen embryo transfer after embryo selection based on morphokinetic versus morphologic criteria for freezing

Quang¹,

Tram²,

Thuy³

et al. 2018

Biomed. Res. Ther.

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Background: Results from the latest meta-analysis, in fresh cycles, showed that the application of time-lapse monitoring (TLM) together with an embryo-evaluating algorithm was associated with a significantly higher rate of ongoing pregnancy and a lower rate of early pregnancy loss. The aim of this study was to compare the clinical outcomes of frozen embryos classified according to morphokinetic versus morphologic criteria. Methods: This was a retrospective cohort study, conducted at IVFAS, An Sinh Hospital, Vietnam, from July 2014 to July 2017. Patients undergoing in vitro fertilization (IVF) treatment with antagonist protocol and having freeze-only on day 5 were included. Exclusion criteria were patients (i) treated with in-vitro maturation, (ii) having obstructive azoospermia, or (iii) having uterine abnormalities. Embryos were cultured up to day 5 in TLM system (Primo Vision, Vitrolife, Sweden) or in benchtop (G185, K System, Denmark). The quality of frozen embryos was evaluated based on morphokinetic or morphologic criteria. In the subsequent cycle, endometrial preparation was done by using exogenous estradiol and progesterone. Embryos were thawed and up to 2 embryos were transferred to the uterus. The primary outcome was ongoing pregnancy. The rate of post-thaw survival, post-thawed good/moderate embryo, clinical pregnancy, implantation, miscarriage and ectopic pregnancy were used as secondary endpoints. Results: A total of 276 patients were recruited, with 138 patients in the morphokinetic group and 138 patients in the morphologic group. Baseline characteristics were comparable between the two groups. There was no significant difference in ongoing pregnancy rate in morphokinetic versus morphologic group (57.2% vs. 60.1%, p=0.71). All secondary outcomes were comparable between the two groups. Conclusion: In frozen day-5 embryo transfer, the clinical outcomes were similar when embryos were classified according to morphokinetic versus morphologic criteria for freezing. Using morphokinetic criteria to select embryos for freezing did not improve the ongoing pregnancy rate, as compared to morphologic criteria.

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“…Embryos are ranked in five groups predicting their ability to develop into a blastocyst with an area under the curve (AUC) of 0.75 and implantation potential with an AUC of 0.65 (indicative of intermediate prediction) [12]. Interestingly, a recent study showed that the KIDScore was superior regarding predicting implantation and ongoing pregnancy rates when compared to only scoring embryo morphology [13].…”

Section: Introductionmentioning

confidence: 99%

Preconceptional Maternal Vegetable Intake and Paternal Smoking Are Associated with Pre-implantation Embryo Quality

et al. 2020

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Inadequate nutrition and lifestyle behaviors, particularly during the periconception period, are associated with a negative impact on embryonic and subsequent fetal development. We investigated the associations between parental nutritional and lifestyle factors and pre-implantation embryo development. A total of 113 women and 41 partners, with a corresponding 490 embryos, who underwent intracytoplasmic sperm injection (ICSI) treatment subscribed to the mHealth coaching platform “Smarter Pregnancy.” At baseline, nutrition and lifestyle behaviors (intake of fruits, vegetables, folic acid, and smoking and alcohol use) were identified and risk scores were calculated. A lower risk score represents healthier behavior. As outcome measure, a time-lapse morphokinetic selection algorithm (KIDScore) was used to rank pre-implantation embryo quality on a scale from 1 (poor) to 5 (good) after being cultured in the Embryoscope™ time-lapse incubator until embryonic day 3. To study the association between the nutritional and lifestyle risk scores and the KIDScore in men and women, we used a proportional odds model. In women, the dietary risk score (DRS), a combination of the risk score of fruits, vegetables, and folic acid, was negatively associated with the KIDScore (OR 0.86 (95% CI 0.76 to 0.98), p = 0.02). This could mainly be attributed to an inadequate vegetable intake (OR 0.76 (95% CI 0.59 to 0.96), p = 0.02). In men, smoking was negatively associated with the KIDscore (OR 0.53 (95% CI 0.33 to 0.85), p < 0.01). We conclude that inadequate periconceptional maternal vegetable intake and paternal smoking significantly reduce the implantation potential of embryos after ICSI treatment. Identifying modifiable lifestyle risk factors can contribute to directed, personalized, and individual recommendations that can potentially increase the chance of a healthy pregnancy.

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External validation of a time-lapse model; a retrospective study comparing embryo evaluation using a morphokinetic model to standard morphology with live birth as endpoint

Cited by 19 publications

References 37 publications

Can novel early non-invasive biomarkers of embryo quality be identified with time-lapse imaging to predict live birth?

Can novel early non-invasive biomarkers of embryo quality be identified with time-lapse imaging to predict live birth?

Comparison of clinical outcome of frozen embryo transfer after embryo selection based on morphokinetic versus morphologic criteria for freezing

Preconceptional Maternal Vegetable Intake and Paternal Smoking Are Associated with Pre-implantation Embryo Quality

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