Costen, N

Czanner, S

Drury, S

Hartshorne, G

Molder, A Leida

E-space: Manchester Metropolitan University's Research Repository

Molder, A Leida and Hartshorne, G and Czanner, S and Costen, N andDrury, S (2017) Image analysis of human embryos grown in vitro as a newnon-invasive tool to determine embryo health. In: 33rd Annual Meeting ofthe European-Society-of-Human-Reproduction-and-Embryology (ESHRE),02 July 2017 - 05 July 2017, Geneva, Switzerland.Downloaded from: http://e-space.mmu.ac.uk/624947/Publisher: Oxford University PressPlease cite the published versionhttps://e-space.mmu.ac.ukImage analysis of human embryos grown in vitroas a new non-invasive tool to determine embryohealthA. Leida Mölder∗ G. Hartshorne† S. CzannerN. Costen S. Drury‡Study question: Which embryo criteria have the most potential for auto-matic monitoring and embryo quality assessment using images captured duringembryo growth in vitro?Summary answer: Detection of syngami, timing of mitosis, blastocyst for-mation and blastomere number are quantifiable attributes. Embryo activity andfragmentation are also detectable but not quantifiable. What is known already:Non-invasive imaging has recently made it possible to monitor embryos con-tinuously without any known consequences to their health. It has been shownthat the timing of key occurrences within the embryo can vary greatly betweenembryos that have similar morphological appearance at the conclusion of therecording period and that embryo morphology can change in a matter of hours,emphasizing the fact that dynamic monitoring is preferred over intermittentmonitoring of embryos. Dynamic monitoring of embryos requires computerizedanalysis but few studies have systematically attempted to map automaticallyextracted embryo imaging criteria to manual detection of the same.Study design, size, duration: Time lapse image series of human embryosfertilized in vitro were acquired as anonymized sequences donated to researchwith ethical approval. Images were analysed for a number of embryo traitknown to correlate with embryo health. Results from computerised analysiswere compared to manual detection of the same trait. The study consisted ofseven studies performed on the same imaging material over a course of threeyears.Participants/materials, setting, methods: Embryos were cultured in 25 lculture media (Origio, Redhill, UK) under mineral oil for up to 6 days, incubatedat 37C in an atmosphere of 5%CO2, 5%O2 and 90%N2. The images were∗Manchester Metropolitan University, School of Computing, Mathematics and DigitalTechnology, Manchester, United Kingdom (ALM, SC and NC)†University Hospitals Coventry and Warwickshire NHS Trust, Centre for ReproductiveMedicine, Coventry, United Kingdom‡Centre for Reproductive Medicine, University Hospitals Coventry and Warwickshire NHSTrust, Coventry, United Kingdom1captured using the Embryoscope(R) time-lapse system (Vitrolife, Gothenburg,Sweden), with 9 focal depth planes, 1525 µm apart, recorded at 20 minuteintervals using a HMC optical set up and a 635 nm LED as light source. Imageswere analyzed using Matlab(R) 7.12.0.635 (R2011a).Main results and the role of chance: Detection accuracy of of syngamiwas 83%, timing of mitosis 80.8% (16 cells), blastocyst formation 71.8% andblastomere number 80.8% (16 cells). Using the timing information, it was pos-sible to measure the time elapsed between divisions to 10.27 h (23 cells), and1.11 h (34 cells), respectively. Detection accuracy for mitosis reduced by cellnumber. 100% of divisions from 1 to 2 cells were detected, 73% from 2 to 3 (or4) cells, 30% from 3 to 4 cells, and 59% from 4 to 5 (or 6) cells. Using the timingof blastocyst and morula formation, we calculated the duration of the morulastage to 1/7 of the duration of the cleavage stage, with some patient variability.Embryo activity and fragmentation were detectable in images but the accuracynot quantifiable, due to the lack of a standardized way to measure these traitsmanually. The automatic counting of blastomere number was semiautomaticand required manual selection of typical images prior to analysis. The count-ing was tested up to the 8 cell stage, in which case the accuracy was 74.9%.The accuracy was less than for other imaging techniques, e.g. using fluorescentmarkers.Limitations, reasons for caution: Images were obtained from a range ofmicroscopy settings using different protocols for embryo cultivation and differentlighting conditions in the microscopy. However, the study cohort was small (38embryos from 7 patients from 3 laboratory settings at the largest). Widerimplications of the findings: Continuous imaging of human embryos growing invitro is being routinely generated as part of IVF cultivation. The material posesa method to study dynamic properties of embryos without having to result toexperimentation on human tissue and has the possibility to provide new methodsto improve IVF success rates.Trial registration number: Ethical approval by Coventry Research EthicsCommittee (04/Q2802/26) and the Human Fertilisation and Embryology Au-thority (R0155).2

Image analysis of human embryos grown in vitro as a new non-invasive tool to determine embryo health

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Image analysis of human embryos grown in vitro as a new non-invasive tool to determine embryo health

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