Development of an artificial intelligence model for predicting the likelihood of human embryo euploidy based on blastocyst images from multiple imaging systems during IVF.

STUDY QUESTION: Can an artificial intelligence (AI) model predict human embryo ploidy status using static images captured by optical light microscopy? SUMMARY ANSWER: Results demonstrated predictive accuracy for embryo euploidy and showed a significant correlation between AI score and euploidy rate, based on assessment of images of blastocysts at Day 5 after IVF. WHAT IS KNOWN ALREADY: Euploid embryos displaying the normal human chromosomal complement of 46 chromosomes are preferentially selected for transfer over aneuploid embryos (abnormal complement), as they are associated with improved clinical outcomes. Currently, evaluation of embryo genetic status is most commonly performed by preimplantation genetic testing for aneuploidy (PGT-A), which involves embryo biopsy and genetic testing. The potential for embryo damage during biopsy, and the non-uniform nature of aneuploid cells in mosaic embryos, has prompted investigation of additional, non-invasive, whole embryo methods for evaluation of embryo genetic status. STUDY DESIGN, SIZE, DURATION: A total of 15 192 blastocyst-stage embryo images with associated clinical outcomes were provided by 10 different IVF clinics in the USA, India, Spain and Malaysia. The majority of data were retrospective, with two additional prospectively collected blind datasets provided by IVF clinics using the genetics AI model in clinical practice. Of these images, a total of 5050 images of embryos on Day 5 of in vitro culture were used for the development of the AI model. These Day 5 images were provided for 2438 consecutively treated women who had undergone IVF procedures in the USA between 2011 and 2020. The remaining images were used for evaluation of performance in different settings, or otherwise excluded for not matching the inclusion criteria. PARTICIPANTS/MATERIALS, SETTING, METHODS: The genetics AI model was trained using static 2-dimensional optical light microscope images of Day 5 blastocysts with linked genetic metadata obtained from PGT-A. The endpoint was ploidy status (euploid or aneuploid) based on PGT-A results. Predictive accuracy was determined by evaluating sensitivity (correct prediction of euploid), specificity (correct prediction of aneuploid) and overall accuracy. The Matthew correlation coefficient and receiver-operating characteristic curves and precision-recall curves (including AUC values), were also determined. Performance was also evaluated using correlation analyses and simulated cohort studies to evaluate ranking ability for euploid enrichment. MAIN RESULTS AND THE ROLE OF CHANCE: Overall accuracy for the prediction of euploidy on a blind test dataset was 65.3%, with a sensitivity of 74.6%. When the blind test dataset was cleansed of poor quality and mislabeled images, overall accuracy increased to 77.4%. This performance may be relevant to clinical situations where confounding factors, such as variability in PGT-A testing, have been accounted for. There was a significant positive correlation between AI score and the proportion of euploid embryos, with very high scoring embryos (9.0-10.0) twice as likely to be euploid than the lowest-scoring embryos (0.0-2.4). When using the genetics AI model to rank embryos in a cohort, the probability of the top-ranked embryo being euploid was 82.4%, which was 26.4% more effective than using random ranking, and ∼13-19% more effective than using the Gardner score. The probability increased to 97.0% when considering the likelihood of one of the top two ranked embryos being euploid, and the probability of both top two ranked embryos being euploid was 66.4%. Additional analyses showed that the AI model generalized well to different patient demographics and could also be used for the evaluation of Day 6 embryos and for images taken using multiple time-lapse systems. Results suggested that the AI model could potentially be used to differentiate mosaic embryos based on the level of mosaicism. LIMITATIONS, REASONS FOR CAUTION: While the current investigation was performed using both retrospectively and prospectively collected data, it will be important to continue to evaluate real-world use of the genetics AI model. The endpoint described was euploidy based on the clinical outcome of PGT-A results only, so predictive accuracy for genetic status in utero or at birth was not evaluated. Rebiopsy studies of embryos using a range of PGT-A methods indicated a degree of variability in PGT-A results, which must be considered when interpreting the performance of the AI model. WIDER IMPLICATIONS OF THE FINDINGS: These findings collectively support the use of this genetics AI model for the evaluation of embryo ploidy status in a clinical setting. Results can be used to aid in prioritizing and enriching for embryos that are likely to be euploid for multiple clinical purposes, including selection for transfer in the absence of alternative genetic testing methods, selection for cryopreservation for future use or selection for further confirmatory PGT-A testing, as required. STUDY FUNDING/COMPETING INTEREST(S): Life Whisperer Diagnostics is a wholly owned subsidiary of the parent company, Presagen Holdings Pty Ltd. Funding for the study was provided by Presagen with grant funding received from the South Australian Government: Research, Commercialisation, and Startup Fund (RCSF). 'In kind' support and embryology expertise to guide algorithm development were provided by Ovation Fertility. 'In kind' support in terms of computational resources provided through the Amazon Web Services (AWS) Activate Program. J.M.M.H., D.P. and M.P. are co-owners of Life Whisperer and Presagen. S.M.D., M.A.D. and T.V.N. are employees or former employees of Life Whisperer. S.M.D, J.M.M.H, M.A.D, T.V.N., D.P. and M.P. are listed as inventors of patents relating to this work, and also have stock options in the parent company Presagen. M.V. sits on the advisory board for the global distributor of the technology described in this study and also received support for attending meetings. TRIAL REGISTRATION NUMBER: N/A.

Controlled drainage and wetlands to reduce agricultural pollution: a lysimetric study.

Controlled drainage and wetlands could be very effective practices to control nitrogen pollution in the low-lying agricultural plains of northeast Italy, but they are not as popular as in other countries. An experiment on lysimeters was therefore carried out in 1996-1998, with the double aim of obtaining local information to encourage the implementation of these practices and to gain more knowledge on the effects involved. Controlled drainage + subirrigation and wetlands were all considered as natural systems where alternative water table management could ameliorate water quality, and were compared with a typical water management scheme for crops in the open field. Eight treatments were considered: free drainage on maize (Zea mays L.) and sugarbeet (Beta vulgaris L.), two treatments of controlled drainage on the same crops, and five wetland treatments using common reed [Phragmites australis (Cav.) Trin. ex Steud.], common cattail (Typha latifolia L.), and tufted sedge (Carex elata All.), with different water table or flooding levels. Lysimeters received about 130 g m 2 of N with fertilization and irrigation water, with small differences among treatments. The effects of treatments were more evident for NO3-N concentrations than for the other chemical parameters (total Kjeldahl nitrogen, pH, and electrical conductivity), with significantly different medians among free drainage (33 mg L(-1)), controlled drainage (1.6 and 2.6 mg L(-1)), and wetlands (0.5-0.7 mg L(-1)). Referring to free drainage, NO3-N losses were reduced by 46 to 63% in controlled drainage and 95% in the average of wetlands. Wetlands also reduced losses of total dissolved solids from 253 g m(-2) (average of crop treatments) to 175 g m(-2) (average of wetlands).

A constructed surface flow wetland for treating agricultural waste waters.

A study was conducted between December 1997 and December 1998 in NE Italy on a 3,200 m2 surface flow vegetated wetland receiving agricultural drainage water from a cultivated field of about 6 ha and occasional applications of organic wastes. The study aimed at evaluating: 1) biomass and seasonal nitrogen dynamics in above- and below-ground biomass of Phragmites australis Cav. (Trin.) and Typha latifolia (L.) grown in separate zones; 2) the effectiveness of the wetland in removing nutrients and sediments coming from the fields; 3) the possibility that wetland could treat occasional applications of organic wastes and 4) to collect some general information on whether the wetland can receive heavy loads coming from storm water runoff. Monthly observations showed that, in both species, aboveground biomass, nitrogen concentration and nitrogen content reached maximum values in summer and minimum values in winter. The contrary occurred in below-ground biomass. The total input of water in the wetland was 66,000 m3 ha(-1), of which 7,700 were drained. Total nitrogen input was 526 kg ha(-1), of which 58 were discharged out of the wetland.

Retropharyngeal abscess after adenoidectomy.

In this paper, we describe a case of retropharyneal abscess with atlantoaxial joint subluxation after an adenoidectomy. This is a rare complication of which the otolaryngologist must be aware because of its potential consequences.

[Arterial pressure in a student population in Aquila]. / Pressione arteriosa in collettivita' scolari di L'Aquila.

The preliminary data of a policentric study for the determination of the blood-pressure values and the risk factors associated with high-blood pressure are reported for establishing a prospective epidemiological research. This research involved 258 children attending nursery, elementary-school in the city of L'Aquila. The weight, height, the triceps-skin-fold, the heart-rate, the blood systolic and diastolic-pressure (fifth tone) were examined. Furthermore the parent who accompanied the child was given a questionnaire in order to define: the general information concerning the child and the parent, the family anamnesis concerning the pathology correlated to the high-blood pressure, the child's weight at birth and the thronging-index (the ratio of the number of the family members with respect to the number of the habitable rooms). The obtained data show, especially for the PAS, higher blood-pressure values (greater than 95. percentile) in the grown-up subjects and in the male. The close correlation between the heart rate, BMI and the weight at birth, on one hand, and the blood-pressure values on the other hand, show, besides the validity of the research carried out, the connection between the blood-pressure situation and other physiological, paraphysiological and pathological factors. In conclusion, observing that a considerably high percentage of subjects with high-blood pressure values (5.8%' is one important result, especially for the future implications that it can have; it has to be defined if this situation has a prediction value of constant high-blood pressure in the adult and in what measure the examined factors influence the stabilization of this pathological situation.