scholarly journals Comparison of DNA methylation patterns of parentally imprinted genes in placenta derived from IVF conceptions in two different culture media

2020 ◽  
Vol 35 (3) ◽  
pp. 516-528
Author(s):  
Callista L Mulder ◽  
Tess M Wattimury ◽  
Aldo Jongejan ◽  
Cindy M de Winter-Korver ◽  
Saskia K M van Daalen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Embryo Culture ◽  
Culture Medium ◽  
Culture Media ◽  
Methylation Status ◽  
Culture Conditions ◽  
Imprinted Genes ◽  
Cpg Sites ◽  
Embryo Culture Medium ◽  
The Mean

Abstract Study question Is there a difference in DNA methylation status of imprinted genes in placentas derived from IVF conceptions where embryo culture was performed in human tubal fluid (HTF) versus G5 culture medium? Summary answer We found no statistically significant differences in the mean DNA methylation status of differentially methylated regions (DMRs) associated with parentally imprinted genes in placentas derived from IVF conceptions cultured in HTF versus G5 culture medium. What is known already Animal studies indicate that the embryo culture environment affects the DNA methylation status of the embryo. In humans, birthweight is known to be affected by the type of embryo culture medium used. The effect of embryo culture media on pregnancy, birth and child development may thus be mediated by differential methylation of parentally imprinted genes in the placenta. Study design, size, duration To identify differential DNA methylation of imprinted genes in human placenta derived from IVF conceptions exposed to HTF or G5 embryo culture medium, placenta samples (n = 43 for HTF, n = 54 for G5) were collected between 2010 and 2012 s as part of a multi-center randomized controlled trial in the Netherlands comparing these embryo culture media. Placenta samples from 69 naturally conceived (NC) live births were collected during 2008–2013 in the Netherlands as reference material. Participants/materials, setting, methods To identify differential DNA methylation of imprinted genes, we opted for an amplicon-based sequencing strategy on an Illumina MiSeq sequencing platform. DNA was isolated and 34 DMRs associated with well-defined parentally imprinted genes were amplified in a two-step PCR before sequencing using MiSeq technology. Sequencing data were analyzed in a multivariate fashion to eliminate possible confounding effects. Main results and the role of chance We found no statistically significant differences in the mean DNA methylation status of any of the imprinted DMRs in placentas derived from IVF conceptions cultured in HTF or G5 culture medium. We also did not observe any differences in the mean methylation status per amplicon nor in the variance in methylation per amplicon between the two culture medium groups. A separate surrogate variable analysis also demonstrated that the IVF culture medium was not associated with the DNA methylation status of these DMRs. The mean methylation level and variance per CpG was equal between HTF and G5 placenta. Additional comparison of DNA methylation status of NC placenta samples revealed no statistically significant differences in mean amplicon and CpG methylation between G5, HTF and NC placenta; however, the number of placenta samples exhibiting outlier methylation levels was higher in IVF placenta compared to NC (P < 0.00001). Also, we were able to identify 37 CpG sites that uniquely displayed outlier methylation in G5 placentas and 32 CpG sites that uniquely displayed outlier methylation in HTF. In 8/37 (G5) and 4/32 (HTF) unique outliers CpGs, a medium-specific unique outlier could be directly correlated to outlier methylation of the entire amplicon. Limitations, reasons for caution Due to practical reasons, not all placentas were collected during the trial, and we collected the placentas from natural conceptions from a different cohort, potentially creating bias. We limited ourselves to the DNA methylation status of 34 imprinted DMRs, and we studied only the placenta and no other embryo-derived tissues. Wider implications of the findings It has often been postulated, but has yet to be rigorously tested, that imprinting mediates the effects of embryo culture conditions on pregnancy, birth and child development in humans. Since we did not detect any statistically significant effects of embryo culture conditions on methylation status of imprinted genes in the placenta, this suggests that other unexplored mechanisms may underlie these effects. The biological and clinical relevance of detected outliers with respect to methylation levels of CpGs and DMR require additional analysis in a larger sample size as well. Given the importance and the growing number of children born through IVF, research into these molecular mechanisms is urgently needed. Study funding/competing interest(s) This study was funded by the March of Dimes grant number #6-FY13-153. The authors have no conflicts of interest. Trial registration number Placental biopsies were obtained under Netherlands Trial Registry number 1979 and 1298.

scholarly journals Genome-Wide Analysis of DNA Methylation in Buccal Cells of Children Conceived through IVF and ICSI

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1912
Author(s):  
Bastien Ducreux ◽  
Jean Frappier ◽  
Céline Bruno ◽  
Abiba Doukani ◽  
Magali Guilleman ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Embryo Culture ◽  
Culture Medium ◽  
Cpg Islands ◽  
Imprinted Genes ◽  
Buccal Cells ◽  
Genome Wide ◽  
Embryo Culture Medium ◽  
Art Display ◽  
Genome Scale

Early life periconceptional exposures during assisted reproductive technology (ART) procedures could alter the DNA methylation profiles of ART children, notably in imprinted genes and repetitive elements. At the genome scale, DNA methylation differences have been reported in ART conceptions at birth, but it is still unclear if those differences remain at childhood. Here, we performed an epigenome-wide DNA methylation association study using Illumina InfiniumEPIC BeadChip to assess the effects of the mode of conception on the methylome of buccal cells from 7- to 8-year-old children (48 children conceived after ART or naturally (control, CTL)) and according to the embryo culture medium in which they were conceived. We identified 127 differentially methylated positions (DMPs) and 16 differentially methylated regions (DMRs) (FDR < 0.05) with low delta beta differences between the two groups (ART vs. CTL). DMPs were preferentially located inside promoter proximal regions and CpG islands and were mostly hypermethylated with ART. We highlighted that the use of distinct embryo culture medium was not associated with DNA methylation differences in childhood. Overall, we bring additional evidence that children conceived via ART display limited genome-wide DNA methylation variation compared with those conceived naturally.

scholarly journals The impact of selected embryo culture conditions on ART treatment cycle outcomes: a UK national study

2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
Catherine M Castillo ◽  
Joyce Harper ◽  
Stephen A Roberts ◽  
Helen C O’Neill ◽  
Edward D Johnstone ◽  
...  
Keyword(s):  
Embryo Culture ◽  
Culture Medium ◽  
Culture Media ◽  
Wald Test ◽  
Culture Conditions ◽  
Oxygen Level ◽  
Success Rates ◽  
Blastocyst Culture ◽  
Clinic Site ◽  
Medium Type

Abstract STUDY QUESTION Are selected embryo culture conditions namely media, oxygen level, and incubator type, associated with IVF live birth rate (LBR) and the health of singleton offspring at birth? SUMMARY ANSWER There were statistically significant differences in LBR between the eight culture media systems analysed; however, none of the embryo culture factors showed statistically significant associations with birth weight (BW) in multivariable regression analyses. WHAT IS KNOWN ALREADY In clinical ART culture media is the initial environment provided for the growth of human embryos. Pre-implantation development is a critical period of developmental plasticity, which could have long-lasting effects on offspring growth and health. Although some studies have shown an impact of culture medium type on BW, the interaction between culture medium type and associated culture conditions on both treatment success rates (LBR) and offspring BW is largely unexplored. This study aimed to examine these factors in a large multicentre national survey capturing the range of clinical practice. STUDY DESIGN, SIZE, DURATION In this cross-sectional study, data from a survey circulated to all UK IVF clinics requesting information regarding culture medium type, incubator type, and oxygen level used in ART between January 2011 and December 2013 were merged with routinely recorded treatment and outcome data held in the Human Fertilisation and Embryology Authority Register up to the end of 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS Forty-six (62%) UK clinics responded to the survey. A total of 75 287 fresh IVF/ICSI cycles were captured, including 18 693 singleton live births. IVF success (live birth, singleton or multiple; LB), singleton gestation and singleton gestation-adjusted BW were analysed using logistic and linear regression models adjusting for patient/treatment characteristics and clinic-specific effects. MAIN RESULTS AND THE ROLE OF CHANCE Culture medium type was shown to have some impact on LBR (multivariable logistic regression, (MRL); post-regression Wald test, P &lt; 0.001), but not on BW (MLR; post-regression Wald test, P = 0.215). However, blastocyst culture had the largest observed effect on odds of LBR (odds ratio (OR) = 1.35, CI: 1.29–1.42), increased the risk of pre-term birth even when controlling for oxygen tension (MLR; OR = 1.42, CI: 1.23–1.63), and gestation-adjusted BW (MLR, β = 38.97 g, CI: 19.42–58.53 g) when compared to cleavage-stage embryo culture. We noted a very strong effect of clinic site on both LBR and BW, thus confounding between treatment practices and clinic site may have masked the effect of culture conditions. LIMITATIONS, REASONS FOR CAUTION Larger datasets with more inter-centre variation are also needed, with key embryo culture variables comprehensively recorded in national treatment registries. WIDER IMPLICATIONS OF THE FINDINGS This study is the largest investigation of laboratory environmental effects in IVF on both LBR and singleton BW. Our findings largely agree with the literature, which has failed to show a consistent advantage of one culture media type over another. However, we noted some association of LBR with medium type, and the duration of embryo exposure to laboratory conditions (blastocyst culture) was associated with both LBR and singleton health at birth. Because of the strong effect of clinic site noted, further randomized controlled trials are needed in order to reliably determine the effect of embryo culture on IVF success rates and the growth and health of subsequent offspring. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the EU FP7 project grant EpiHealthNet (FP7-PEOPLE-2012-ITN -317 146). The authors have no competing interests to declare.

P–146 Differential impact of three embryo culture media for IVF on in vitro development and perinatal outcome: a single-center RCT

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Murakami ◽  
K Tanaka ◽  
H Otsubo ◽  
S Mizumoto ◽  
Y Nagao ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Embryo Culture ◽  
Culture Medium ◽  
Culture Media ◽  
Blastocyst Stage ◽  
Cleavage Stage ◽  
Embryo Culture Medium ◽  
Cleavage Stage Embryo ◽  
Stage Embryo

Abstract Study question This report provides updated data from an RCT determining which embryo culture medium yields optimal IVF outcomes. Summary answer Embryo culture systems used for IVF differentially affected preimplantation development and resultant obstetric and perinatal outcomes, including birthweights of live-born singletons. What is known already Currently, multiple embryo culture medium systems are in use for IVF, raising questions regarding which is optimal. However, the ability of a medium to yield preimplantation embryos is not necessarily indicative of embryo viability. For example, supplementation of medium with serum was commonly used to increase animal blastocyst yields, but this impaired embryonic, fetal, and offspring health. In humans, medium composition and culture duration can influence IVF efficacy and offspring phenotype. Given the importance of culture systems in determining clinical outcomes, existing data regarding differential culture system impacts are insufficient and additional well-designed studies are required. Study design, size, duration Between February 2016 and August 2017, 795 couples undergoing their first autologous clinical IVF cycle and freeze-all strategy were recruited. Participants were randomized via computer-generated tables into three groups. Following standard oocyte retrieval and IVF/ICSI procedures, embryos were cultured using three different culture media, G1 Plus/G2 Plus (G1/G2; Vitrolife), Global Total (GT; LifeGlobal), or Sequential Cleav/Sequential Blast (SC/SB; Origio). Thirty-eight patients exhibiting no 2PN oocytes following insemination or those undergoing fresh embryo transfers were excluded. Participants/materials, setting, methods For patients yielding a single good-quality cleavage-stage (day–2 or day–3) embryo, that cleavage-stage embryo was vitrified. For patients yielding two or more good-quality cleavage-stage embryos, two or less good-quality cleavage-stage embryos were vitrified. The culture period of the remaining embryos was extended, and all good-quality blastocyst-stage (day–5 or day–6) embryos were vitrified. This report presents data for vitrified embryo transfer performed until the end of December 2020. Main results and the role of chance The mean per-cycle vitrified embryo yield (± SD) was comparable between groups for cleavage-stage embryos, but significantly different for blastocyst-stage embryos (G1/G2: 1.69 ± 2.2, GT: 2.53 ± 3.01, SC/SB: 2.04 ± 2.42; P = 0.001). Following vitrified cleavage- or blastocyst-stage embryo transfers, biochemical pregnancy rates were significantly different between groups (G1/G2: 55.6%, GT: 59.1%, SC/SB: 46.2%; P = 0.011). Furthermore, a between-group trend towards different live birth rates was observed (G1/G2: 41.7%, GT: 42.1%, SC/SB: 33.1%; P = 0.063). Of 382 live births, data for first-borns (n = 323; 295 singletons and 14 twin-pairs) are reported here. Perinatal data did not differ significantly between groups for both cleavage- and blastocyst-stage embryo transfers, including gestational age- and gender-adjusted singleton birthweight (z-score). Following multiple linear regression (including selected covariates), adjusted mean singleton birthweights were significantly lower in the G1/G2 and GT groups than in the SC/SB group (by 131 g; P = 0.011 and 110 g; P = 0.032, respectively) and tended to be lower for cleavage-stage embryo transfers than for blastocyst-stage embryo transfers (by 102 g; P = 0.053). Limitations, reasons for caution A larger cohort size and longer-term follow-up are required to verify and further elucidate the impact of embryo culture methods on child health. Such studies will raise awareness regarding the sensitivity of in vitro-cultured human embryos to their environment, ultimately resulting in practices that decrease IVF risks to offspring. Wider implications of the findings: Pregnancy outcome of the medium yielding fewer blastocysts was comparable or superior to that of other media, highlighting the importance of differentiating between the ability to support preimplantation development versus the ability to yield viable embryos. Embryo culture medium had a greater impact than embryo transfer stage on live birthweight. Trial registration number UMIN000020910

DNA methylation defects in spermatozoa of male partners from couples experiencing recurrent pregnancy loss

2020 ◽  
Author(s):  
Kushaan Khambata ◽  
Sanketa Raut ◽  
Sharvari Deshpande ◽  
Sweta Mohan ◽  
Shobha Sonawane ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Methylation Status ◽  
Differentially Methylated Region ◽  
Imprinted Genes ◽  
Epigenetic Factors ◽  
Cpg Sites ◽  
Sperm Dna ◽  
Sperm Dna Methylation

Abstract STUDY QUESTION What is the sperm DNA methylation status of imprinted genes in male partners from couples experiencing recurrent pregnancy loss (RPL)? SUMMARY ANSWER Aberrations in sperm DNA methylation status of several imprinted genes, such as insulin like growth factor-2-H19 differentially methylated region (IGF2-H19 DMR), intergenic differentially methylated region (IG-DMR), mesoderm specific transcript (MEST), zinc finger protein which regulates apoptosis and cell cycle arrest (ZAC), DMR in intron 10 of KCNQ1 gene (KvDMR), paternally expressed gene 3 (PEG3) and paternally expressed gene 10 (PEG10), as well as decreased sperm global 5-methylcytosine (5mC) levels, are associated with RPL. WHAT IS KNOWN ALREADY RPL is defined as loss of two or more pregnancies, affecting 1–2% of couples of reproductive age. Although there are several maternal and paternal aetiological factors contributing to RPL, nearly 50% of the cases remain idiopathic. Thus, there is a need to identify putative paternal factors that could be contributing towards pregnancy loss in cases of idiopathic RPL. STUDY DESIGN, SIZE, DURATION In this case–control study, 112 couples undergoing RPL with no identifiable cause were recruited from September 2015 to May 2018. The control group comprised of 106 healthy proven fertile couples with no history of infertility or miscarriage. PARTICIPANTS/MATERIALS, SETTING, METHODS In this study, we investigated the paternal genetic and epigenetic factors that could be associated with RPL. We studied DNA methylation, by pyrosequencing, of selected imprinted genes implicated in embryo development, such as IGF2-H19 DMR, IG-DMR, MEST, ZAC, KvDMR, PEG3, PEG10 and small nuclear ribonucleoprotein polypeptide N (SNRPN) in sperm of men whose partners present RPL. Global DNA methylation in sperm was evaluated by studying 5mC content and long interspersed nuclear element 1 (LINE1) promoter methylation. We also studied polymorphisms by pyrosequencing in the IGF2-H19 DMR as well in the IGF2 promoter in both groups. MAIN RESULTS AND THE ROLE OF CHANCE In the RPL group, we found a significant decrease in the global sperm 5mC levels and significant decrease in DNA methylation at three CpG sites in LINE1 promoter. For IGF2-H19 DMR and IG-DMR, a significant decrease in sperm DNA methylation at specific CpG sites was observed in RPL group. For maternally imprinted genes like MEST, ZAC, KvDMR, PEG3 and PEG10 hypermethylation was noted. Polymorphism studies for IGF2-H19 DMR and IGF2 revealed significant differences in the genotypic frequencies in males. LIMITATIONS, REASONS FOR CAUTION In this study, we analysed the methylation levels of selected candidate imprinted genes implicated in embryo development. Detection of methylation changes occurring at the genome-wide level may reveal further candidate genes having a better distinction between the control and study groups. WIDER IMPLICATIONS OF THE FINDINGS Our study demonstrates that certain polymorphisms and aberrant sperm methylation status in imprinted genes are associated with RPL and could contribute to the aetiology of RPL. This study suggests that investigation of paternal genetic and epigenetic factors could be useful in identification of possible causes of idiopathic RPL. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Department of Science and Technology-Science and Engineering Research Board (EMR/2014/000145) and National Institute for Research in Reproductive Health intramural funds (RA/872/01-2020). All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

scholarly journals Isolation and Characterization of Functionally Active Extracellular Vesicles from Culture Medium Conditioned by Bovine Embryos In Vitro

2018 ◽  
Vol 20 (1) ◽  
pp. 38 ◽  
Author(s):  
Krishna Pavani ◽  
An Hendrix ◽  
Wim Van Den Broeck ◽  
Liesbeth Couck ◽  
Katarzyna Szymanska ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Embryo Culture ◽  
Culture Medium ◽  
Culture Media ◽  
Apoptotic Cell ◽  
Bovine Embryo ◽  
Bovine Embryos ◽  
Isolation And Characterization ◽  
Embryo Culture Medium

Extracellular vesicles (EVs) play a possible role in cell–cell communication and are found in various body fluids and cell conditioned culture media. The aim of this study was to isolate and characterize EVs in culture medium conditioned by bovine embryos in group and to verify if these EVs are functionally active. Initially, ultracentrifuged bovine serum albumin (BSA) containing medium was selected as suitable EV-free embryo culture medium. Next, EVs were isolated from embryo conditioned culture medium by OptiPrepTM density gradient ultracentrifugation. Isolated EVs were characterized by nanoparticle tracking analysis, western blotting, transmission, and immunoelectron microscopy. Bovine embryo-derived EVs were sizing between 25–230 nm with an average concentration of 236.5 ± 1.27 × 108 particles/mL. Moreover, PKH67 EV pre-labeling showed that embryo-secreted EVs were uptaken by zona-intact bovine embryos. Since BSA did not appear to be a contaminating EV source in culture medium, EV functionality was tested in BSA containing medium. Individual embryo culture in BSA medium enriched with EVs derived from conditioned embryo culture medium showed significantly higher blastocyst rates at day 7 and 8 together with a significantly lower apoptotic cell ratio. In conclusion, our study shows that EVs play an important role in inter embryo communication during bovine embryo culture in group.

scholarly journals Sonic hedgehog supplementation of oocyte and embryo culture media enhances development of IVF porcine embryos

Reproduction ◽  
2011 ◽  
Vol 142 (1) ◽  
pp. 87-97 ◽  
Author(s):  
Ngoc Tan Nguyen ◽  
Neng-Wen Lo ◽  
Sing-Ping Chuang ◽  
Ya-Lan Jian ◽  
Jyh-Cherng Ju
Keyword(s):  
Embryonic Development ◽  
Sonic Hedgehog ◽  
Embryo Culture ◽  
Culture Medium ◽  
Culture Media ◽  
Total Cell ◽  
Cell Numbers ◽  
Histone 3 ◽  
Embryo Culture Medium

We investigated the expression of sonic hedgehog (SHH) receptor PTCH1 and its co-receptor smoothened (SMO) in fertilized porcine embryos. Effects of exogenous SHH on embryonic development and expressions of survival- and pluripotency-related genes were also determined. We found that PTCH1 and SMO are expressed from two-cell to blastocyst embryos. When oocytes or fertilized embryos were respectively cultured in the maturation or embryo culture medium supplemented with SHH (0.5 μg/ml), their blastocyst rates and total cell numbers increased (P<0.05) compared with the untreated control. When cultured simultaneously in thein vitromaturation (IVM) andin vitroculture (IVC) media supplemented with SHH, the oocytes gained increased blastocyst rates and total cell numbers in an additive manner, with reduced apoptotic indices (P<0.05). Interestingly, SHH treatment did not affect the expression of theBCL2L1(BCL-XL) gene, yet reducedBAXexpression. Blastocysts cultured with various SHH regimes had similar pluripotency-related gene (POU5F1(OCT-4) andCDX2) expression levels, but blastocysts derived from SHH treatment during IVM had higherZPF42(REX01) expression (P<0.05). The highestZPF42expression was observed in the blastocysts derived from SHH-supplemented IVC and from dual IVM and IVC treatments. The levels of acetylated histone 3 (AcH3K9/K14) increased in the two-cell and the four-cell embryos when IVM and/or IVC media were supplemented with SHH (P<0.05). Our findings indicate that SHH conferred a beneficial effect on preimplantation development of porcine embryos, particularly when both IVM and IVC media were supplemented with SHH, and the effects may be further carried over from IVM to the subsequent embryonic development.

P-203 Applying artificial intelligence for ploidy prediction: The concentration of IL-6 in spent culture medium, blastocyst morphological grade and embryo morphokinetics as variables under consideration

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
B Aparicio Ruiz ◽  
L Bori ◽  
E Paya ◽  
M A Valera ◽  
A Quiñonero ◽  
...  
Keyword(s):  
Embryo Culture ◽  
Culture Medium ◽  
Culture Media ◽  
General Description ◽  
Ann Model ◽  
Non Invasive ◽  
Morphokinetic Parameters ◽  
Testing Dataset ◽  
Standard Deviations ◽  
The Impact

Abstract Study question Would it be possible to predict embryo ploidy by taking into account conventional morphological and morphokinetic parameters together with IL-6 concentration in spent culture medium? Summary answer Our artificial neural network (ANN) trained with blastocyst morphology, embryo morphokinetics and IL-6 concentration distinguished between euploid/aneuploid embryos in 65% of the testing dataset. What is known already The analysis of spent embryo culture media represents the protein and metabolic state of the embryo and could be a non-invasive method of obtaining information about embryo quality. The impact of the presence/absence of several proteins in embryo culture samples over clinical results has been widely studied. The IL-6 is one of the most mentioned protein for its effect on embryo development, implantation and likelihood of achieving a live birth. In this initial attempt, we examined the predictive value for euploidy of a model that took into account the concentration of IL-6 in the spent culture medium. Study design, size, duration This prospective study included 319 embryos with PGT-A results. Out of the total, 127 were euploid and 192 aneuploid embryos. Concentration of IL-6 in spent embryo culture media (collected on the day of trophectoderm biopsy-fifth/sixth day of development), morphokinetic parameters (division time to 2 cells-t2; to 3 cells-t3, to 4 cells-t4; to 5 cells-t5 and time of blastocyst formation-tB) and blastocyst morphological grade (according to ASEBIR criteria) were considered to predict the embryo ploidy. Participants/materials, setting, methods Embryos were cultured in EmbryoScope. The chromosome analysis was performed using next-generation sequence technology. The concentration of IL-6 was measured in 20µL of spent embryo culture media with ELISA kits. Morphokinetic parameters were automatically annotated and the blastocyst morphology was evaluated by senior embryologists based on blastocele expansion, inner cell mass and trophectoderm quality. All the embryos were divided into 70% for training, 15% for validating and 15% for testing our ANN model with MatLab®. Main results and the role of chance The general description for the euploid embryo population was the following: 2% of the embryos were graded as A, 71% were graded as B and 28% were graded as C; the means and standard deviations were 25.32±2.97 hours (h) for t2, 35.33±5.15h for t3, 37.30±5.43h for t4, 48.24±6.62h for t5 and 103.93±12.8h for tB; and the average of IL-6 concentration was 1.51±0.70 pg/ml. The general description for the aneuploid embryo population was the following: 1% of the embryos were graded as A, 48% were graded as B and 51% were graded as C; the means and standard deviations were 26.13±3.51h for t2, 36.70±4.29h for t3, 38.20±4.24h for t4, 49.86±6.89h for t5 and 107.10±8.29h for tB; and the average of IL-6 concentration was 1.47±0.71 pg/ml. Our ANN model showed a higher general success rate as we increased the variables considered in the final prediction of euploid embryos. The accuracy, sensitivity and specificity for the testing dataset were: 0.60, 0.12 and 0.87 with morphokinetic parameters; 0.63, 0.24 and 0.93 with morphokinetics and IL-6 concentration; and 0.65, 0.16 and 0.96 with morphokinetics, IL-6 concentration and blastocyst morphological grade. Limitations, reasons for caution The low sensitivity and high specificity achieved in our models indicated that they were more capable of detecting aneuploid than euploid embryos. As this was a preliminary study, the small number of embryos included in the test (n = 48) was also a limitation. Wider implications of the findings The results showed that our model tended to classify the embryos as aneuploid. More euploid embryos would be necessary to train our model and achieve better results in the prediction of chromosomally normal embryos. Further studies with large number of embryos and additional variables could improve the non-invasive ploidy prediction. Trial registration number not applicable

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