Categories
Nevin Manimala Statistics

Development and preliminary validation of the Dietary Self-management Behavior Questionnaire (DSMBQ) for breast cancer patients during chemotherapy: three rounds of survey

BMC Public Health. 2024 Dec 24;24(1):3579. doi: 10.1186/s12889-024-21128-x.

ABSTRACT

BACKGROUND: Adverse effects during chemotherapy severely impact the daily diet of breast cancer (BC) patients. Engaging in dietary self-management is crucial for healthy lifestyle and recovery. This study aims to create the Dietary Self-management Behavior Questionnaire (DSMBQ) and preliminarily validate its reliability, validity, and discriminative ability for BC patients undergoing chemotherapy.

METHODS: The questionnaire was developed through a scoping review, patient interviews, and referenced to previous scales. The initial draft item pool underwent two rounds of Delphi expert consultations, creating the draft DSMBQ with 6 predefined dimensions and 98 items. Subsequently, the draft questionnaire underwent three rounds of investigation. The results from the first two surveys were utilized for item selection, the third was to assess the construct of the final DSMBQ. Three groups (n = 158, 385, and 771) were conveniently sampled from three hospitals in Xi’an and Zhengzhou cities. Lastly, 150, 378, and 760 participants, respectively, completed valid questionnaires. Exploratory factor analysis and variability analysis were used to assess the draft questionnaire, and the structure was further examined through confirmatory factor analysis.

RESULTS: The final DSMBQ comprised 22 items organized into 4 dimensions. The cumulative variance contribution rate totaled 62.96%. The Cronbach’s α demonstrated high internal consistency at 0.91, while the split-half reliability coefficient was 0.83, and the test-retest reliability coefficient reached 0.94. Correlation coefficients between the scores of each dimension and the total score ranged from 0.697 to 0.751. With the exception of the normed fit index (NFI) and the non-normed fit index (NNFI) at 0.89 (close to 0.90), all other indicators met statistical requirements. Patients exhibited varying average scores for each dimension of the DSMBQ based on differences in age, education level, Body Mass Index (BMI), menopausal status, and cancer stage (P < 0.05).

CONCLUSION: The DSMBQ demonstrated good reliability, validation, and discriminative ability in Chinese BC patients undergoing chemotherapy. Tailored to the cultural context, the DSMBQ emerges as a high-quality tool for the nuanced assessment of dietary self-management in BC patients by focusing on lifestyle behavior changes. It holds the potential to enhance subjective initiative and confidence, facilitating increased patient participation in their healthcare.

PMID:39719570 | DOI:10.1186/s12889-024-21128-x

Categories
Nevin Manimala Statistics

Care-Seeking Action after Helicobacter pylori Testing among a High-Risk Indigenous Population: A Cross-Sectional Study Follow-up

Am J Trop Med Hyg. 2024 Dec 24:tpmd240393. doi: 10.4269/ajtmh.24-0393. Online ahead of print.

ABSTRACT

Helicobacter pylori is one of the most common infectious agents linked to any malignancy. Recent studies report higher H. pylori prevalence and gastric cancer incidence rates in the Navajo Nation than in general U.S. populations. Little is known about barriers to care and treatment. Participants of the 2022 Navajo Healthy Stomach Project who had a positive urea breath test for H. pylori were contacted after 6 months to assess health care services sought, treatment received, and barriers to accessing care. Descriptive statistics identified perceived barriers to care seeking and treatment. Of individuals consented to recontact, 83 were surveyed (69.8% response rate). Just over half (52.8%) reported following up with an allopathic clinician. The most common reasons for not seeking care were lack of time (37.5%) and forgetting (25.0%). Care seeking was more common among those who felt that H. pylori was linked to their gastrointestinal symptoms (P = 0.03) or those less concerned about adverse effects of antibiotics (P = 0.07). Community engagement throughout the research process and intentionally sharing research finding with communities may be strategies to reduce barriers to care seeking after a positive H. pylori infection diagnosis.

PMID:39719117 | DOI:10.4269/ajtmh.24-0393

Categories
Nevin Manimala Statistics

Impact of Artificial Intelligence-Generated Content Labels On Perceived Accuracy, Message Credibility, and Sharing Intentions for Misinformation: Web-Based, Randomized, Controlled Experiment

JMIR Form Res. 2024 Dec 24;8:e60024. doi: 10.2196/60024.

ABSTRACT

BACKGROUND: The proliferation of generative artificial intelligence (AI), such as ChatGPT, has added complexity and richness to the virtual environment by increasing the presence of AI-generated content (AIGC). Although social media platforms such as TikTok have begun labeling AIGC to facilitate the ability for users to distinguish it from human-generated content, little research has been performed to examine the effect of these AIGC labels.

OBJECTIVE: This study investigated the impact of AIGC labels on perceived accuracy, message credibility, and sharing intention for misinformation through a web-based experimental design, aiming to refine the strategic application of AIGC labels.

METHODS: The study conducted a 2×2×2 mixed experimental design, using the AIGC labels (presence vs absence) as the between-subjects factor and information type (accurate vs inaccurate) and content category (for-profit vs not-for-profit) as within-subjects factors. Participants, recruited via the Credamo platform, were randomly assigned to either an experimental group (with labels) or a control group (without labels). Each participant evaluated 4 sets of content, providing feedback on perceived accuracy, message credibility, and sharing intention for misinformation. Statistical analyses were performed using SPSS version 29 and included repeated-measures ANOVA and simple effects analysis, with significance set at P<.05.

RESULTS: As of April 2024, this study recruited a total of 957 participants, and after screening, 400 participants each were allocated to the experimental and control groups. The main effects of AIGC labels were not significant for perceived accuracy, message credibility, or sharing intention. However, the main effects of information type were significant for all 3 dependent variables (P<.001), as were the effects of content category (P<.001). There were significant differences in interaction effects among the 3 variables. For perceived accuracy, the interaction between information type and content category was significant (P=.005). For message credibility, the interaction between information type and content category was significant (P<.001). Regarding sharing intention, both the interaction between information type and content category (P<.001) and the interaction between information type and AIGC labels (P=.008) were significant.

CONCLUSIONS: This study found that AIGC labels minimally affect perceived accuracy, message credibility, or sharing intention but help distinguish AIGC from human-generated content. The labels do not negatively impact users’ perceptions of platform content, indicating their potential for fact-checking and governance. However, AIGC labeling applications should vary by information type; they can slightly enhance sharing intention and perceived accuracy for misinformation. This highlights the need for more nuanced strategies for AIGC labels, necessitating further research.

PMID:39719080 | DOI:10.2196/60024

Categories
Nevin Manimala Statistics

Large Language Models May Help Patients Understand Peer-Reviewed Scientific Articles About Ophthalmology: Development and Usability Study

J Med Internet Res. 2024 Dec 24;26:e59843. doi: 10.2196/59843.

ABSTRACT

BACKGROUND: Adequate health literacy has been shown to be important for the general health of a population. To address this, it is recommended that patient-targeted medical information is written at a sixth-grade reading level. To make well-informed decisions about their health, patients may want to interact directly with peer-reviewed open access scientific articles. However, studies have shown that such text is often written with highly complex language above the levels that can be comprehended by the general population. Previously, we have published on the use of large language models (LLMs) in easing the readability of patient-targeted health information on the internet. In this study, we continue to explore the advantages of LLMs in patient education.

OBJECTIVE: This study aimed to explore the use of LLMs, specifically ChatGPT (OpenAI), to enhance the readability of peer-reviewed scientific articles in the field of ophthalmology.

METHODS: A total of 12 open access, peer-reviewed papers published by the senior authors of this study (ET and RA) were selected. Readability was assessed using the Flesch-Kincaid Grade Level and Simple Measure of Gobbledygook tests. ChatGPT 4.0 was asked “I will give you the text of a peer-reviewed scientific paper. Considering that the recommended readability of the text is 6th grade, can you simplify the following text so that a layperson reading this text can fully comprehend it? – Insert Manuscript Text -“. Appropriateness was evaluated by the 2 uveitis-trained ophthalmologists. Statistical analysis was performed in Microsoft Excel.

RESULTS: ChatGPT significantly lowered the readability and length of the selected papers from 15th to 7th grade (P<.001) while generating responses that were deemed appropriate by expert ophthalmologists.

CONCLUSIONS: LLMs show promise in improving health literacy by enhancing the accessibility of peer-reviewed scientific articles and allowing the general population to interact directly with medical literature.

PMID:39719077 | DOI:10.2196/59843

Categories
Nevin Manimala Statistics

Characteristics and outcomes of patients with Guillain-Barré syndrome who were admitted to the intensive care unit: a retrospective observational study

J Int Med Res. 2024 Dec;52(12):3000605241306655. doi: 10.1177/03000605241306655.

ABSTRACT

OBJECTIVE: To evaluate characteristics and outcomes in critically ill patients with Guillain-Barré syndrome (GBS).

METHODS: Consecutive adults with GBS who required intensive care unit (ICU) admission at a tertiary-care hospital between 1999 and 2020 were enrolled into this retrospective cohort study. Demographics, clinical data and patient outcomes were compared between patients who did or did not receive mechanical ventilation (MV).

RESULTS: During the study period, the number of ICU admissions gradually rose from approximately 900 to 3000 annually. Forty-three patients had GBS and were included, of whom, 27 (62.8%) received MV for a median of 13 days. The MV group stayed longer in the ICU (median, 26 versus 6 days) and in the hospital (median, 120 versus 39 days) than the non-MV group. Most patients in the MV group (22 [81.5%]) required tracheostomy. At maximum follow-up, Hughes Functional Grading scores were 0 (full recovery) in 11 patients (25.5%), 1-3 in 18 (41.8%), 4-5 in 12 (27.9%), and 6 (death) in two (4.6%, both in the MV group), with higher median Hughes score in the MV group (3 versus 0.5). Complications during ICU and hospital stay included: veinous thromboembolism in five (11.6%), gastrointestinal bleeding in three (7.0%), bacteremia in five (11.6%), bedsore in one (2.3%), and GBS-treatment side effects in four (9.4%) patients; all of these complications occurred within the MV group.

CONCLUSIONS: GBS was an uncommon reason for ICU admission. The findings highlight significant morbidity with GBS, particularly among patients who need MV.

PMID:39719074 | DOI:10.1177/03000605241306655

Categories
Nevin Manimala Statistics

Exploring the epidemiological burden of RSV pre- and post-COVID-19 pandemic: A Jordanian tertiary hospital experience

J Int Med Res. 2024 Dec;52(12):3000605241306405. doi: 10.1177/03000605241306405.

ABSTRACT

OBJECTIVES: To describe changes in respiratory syncytial virus (RSV) epidemiology, its associated clinical outcomes and predictors of severe acute lower respiratory tract infection (ALRTI) pre- and post-COVID-19.

METHODS: In this retrospective cohort, we analysed data from electronic medical record of children <5 years who were hospitalized at Jordan University Hospital with RSV-associated ALRTI from 2018 to 2022.

RESULTS: 325 inpatients with respiratory infections were included. Rate of RSV infections decreased from 74% pre-pandemic to 30% post-pandemic. Patients diagnosed with ALRTI post-COVID had significantly higher SpO2, less chronic disease, lower temperature and respiratory rate at admission and fewer days in hospital compared with those diagnosed pre-COVID. Furthermore, patients diagnosed pre-pandemic were significantly more likely to have abnormal X-rays, used more antibiotics and antivirals, and had higher rates of severe disease than those with infection post-COVID.

CONCLUSION: COVID-19 and its associated social restriction measures led to changes in RSV epidemiology, characterized by a decline in rates and clinical severity in the post-pandemic period. However, further studies are needed to characterize the impact of COVID-19 on subsequent RSV seasons.

PMID:39719069 | DOI:10.1177/03000605241306405

Categories
Nevin Manimala Statistics

Gretl-variation graph evaluation TooLkit

Bioinformatics. 2024 Dec 24:btae755. doi: 10.1093/bioinformatics/btae755. Online ahead of print.

ABSTRACT

MOTIVATION: As genome graphs are powerful data structures for representing the genetic diversity within populations, they can help identify genomic variations that traditional linear references miss, but their complexity and size makes the analysis of genome graphs challenging. We sought to develop a genome graph analysis tool that helps these analyses to become more accessible by addressing the limitations of existing tools. Specifically, we improve scalability and user-friendliness, and we provide many new statistics tailored to variation graphs for graph evaluation, including sample-specific features.

RESULTS: We developed an efficient, comprehensive, and integrated tool, gretl, to analyze genome graphs and gain insights into their structure and composition by providing a wide range of statistics. gretl can be utilised to evaluate different graphs, compare the output of graph construction pipelines with different parameters, as well as perform an in-depth analysis of individual graphs, including sample-specific analysis. With the assistance of gretl, novel patterns of genetic variation and potential regions of interest can be identified, for later, more detailed inspection. We demonstrate that gretl outperforms other tools in terms of speed, particularly for larger genome graphs.

AVAILABILITY: Commented Rust source code and documentation is available under MIT license at https://github.com/MoinSebi/gretl together with Python scripts and step-by-step usage examples. The package is available at Bioconda for easy installation.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:39719064 | DOI:10.1093/bioinformatics/btae755

Categories
Nevin Manimala Statistics

Identification of plasma protein biomarkers for endometriosis and the development of statistical models for disease diagnosis

Hum Reprod. 2024 Dec 24:deae278. doi: 10.1093/humrep/deae278. Online ahead of print.

ABSTRACT

STUDY QUESTION: Can a panel of plasma protein biomarkers be identified to accurately and specifically diagnose endometriosis?

SUMMARY ANSWER: A novel panel of 10 plasma protein biomarkers was identified and validated, demonstrating strong predictive accuracy for the diagnosis of endometriosis.

WHAT IS KNOWN ALREADY: Endometriosis poses intricate medical challenges for affected individuals and their physicians, yet diagnosis currently takes an average of 7 years and normally requires invasive laparoscopy. Consequently, the need for a simple, accurate non-invasive diagnostic tool is paramount.

STUDY DESIGN, SIZE, DURATION: This study compared 805 participants across two independent clinical populations, with the status of all endometriosis and symptomatic control samples confirmed by laparoscopy. A proteomics workflow was used to identify and validate plasma protein biomarkers for the diagnosis of endometriosis.

PARTICIPANTS/MATERIALS, SETTING, METHODS: A proteomics discovery experiment identified candidate biomarkers before a targeted mass spectrometry assay was developed and used to compare plasma samples from 464 endometriosis cases, 153 general population controls, and 132 symptomatic controls. Three multivariate models were developed: Model 1 (logistic regression) for endometriosis cases versus general population controls, Model 2 (logistic regression) for rASRM stage II to IV (mild to severe) endometriosis cases versus symptomatic controls, and Model 3 (random forest) for stage IV (severe) endometriosis cases versus symptomatic controls.

MAIN RESULTS AND THE ROLE OF CHANCE: A panel of 10 protein biomarkers were identified across the three models which added significant value to clinical factors. Model 3 (severe endometriosis vs symptomatic controls) performed the best with an area under the receiver operating characteristic curve (AUC) of 0.997 (95% CI 0.994-1.000). This model could also accurately distinguish symptomatic controls from early-stage endometriosis when applied to the remaining dataset (AUCs ≥0.85 for stage I to III endometriosis). Model 1 also demonstrated strong predictive performance with an AUC of 0.993 (95% CI 0.988-0.998), while Model 2 achieved an AUC of 0.729 (95% CI 0.676-0.783).

LIMITATIONS, REASONS FOR CAUTION: The study participants were mostly of European ethnicity and the results may be biased from undiagnosed endometriosis in controls. Further analysis is required to enable the generalizability of the findings to other populations and settings.

WIDER IMPLICATIONS OF THE FINDINGS: In combination, these plasma protein biomarkers and resulting diagnostic models represent a potential new tool for the non-invasive diagnosis of endometriosis.

STUDY FUNDING/COMPETING INTEREST(S): Subject recruitment at The Royal Women’s Hospital, Melbourne, was supported in part by funding from the Australian National Health and Medical Research Council (NHMRC) project grants GNT1105321 and GNT1026033 and Australian Medical Research Future Fund grant no. MRF1199715 (P.A.W.R., S.H.-C., and M.H.). Proteomics International has filed patent WO 2021/184060 A1 that relates to endometriosis biomarkers described in this manuscript; S.B., R.L., and T.C. declare an interest in this patent. J.I., S.B., C.L., D.I., H.L., K.P., M.D., M.M., M.R., P.T., R.L., and T.C. are shareholders in Proteomics International. Otherwise, the authors have no conflicts of interest.

TRIAL REGISTRATION NUMBER: N/A.

PMID:39719050 | DOI:10.1093/humrep/deae278

Categories
Nevin Manimala Statistics

Biosimilars versus the originator of follitropin alfa for ovarian stimulation in ART: a systematic review and meta-analysis

Hum Reprod. 2024 Dec 24:deae274. doi: 10.1093/humrep/deae274. Online ahead of print.

ABSTRACT

STUDY QUESTION: Is the probability of pregnancy different between women using biosimilars versus the originator of follitropin alfa for ovarian stimulation in ART?

SUMMARY ANSWER: Meta-analysis of eight randomized clinical trials (RCTs) suggests that live birth, clinical, and ongoing pregnancy rates are significantly lower with biosimilars of follitropin alfa compared to the originator.

WHAT IS KNOWN ALREADY: All biosimilars of follitropin alfa have received regulatory approval by demonstrating non-inferiority in the number of retrieved oocytes compared to the originator. Nevertheless, the most clinically relevant outcome in ART for both clinicians and patients is live birth. A meta-analysis published in 2021 suggested that biosimilars of follitropin alfa are associated with lower live birth rates compared to the originator. Since then, more relevant RCTs have been published, and thus an updated critical synthesis of the available evidence is urgently warranted.

STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis were performed to compare biosimilars versus the originator of follitropin alfa in women undergoing ovarian stimulation for ART. A literature search was conducted until January 2024 in MEDLINE, Embase, Cochrane CENTRAL, Scopus, Web of Science, WHO, Clinicaltrials.gov, and others to identify eligible RCTs. The primary outcome was live birth. Secondary outcomes included clinical and ongoing pregnancy, duration of gonadotrophin administration and total FSH dose, number of oocytes retrieved, and ovarian hyperstimulation syndrome (OHSS).

PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were extracted independently by two reviewers. Quality was assessed using the RoB-2 Tool by Cochrane, and a sensitivity analysis was performed by excluding studies having high risk of bias. Meta-analysis was performed using the random or fixed effects model depending on the presence or not of significant (>50%) statistical heterogeneity (I2). Results were combined using the intention-to-treat principle and are reported as risk ratio (RR) or weighted-mean-difference (WMD) with 95% CIs.

MAIN RESULTS AND THE ROLE OF CHANCE: Eight RCTs (n = 2987) (published between 2015 and 2023) were identified, assessing seven biosimilar products of follitropin alfa. The number of patients included in the eligible studies ranged from 100 to 1100. Three of the RCTs were deemed to be at high risk of bias. The duration of gonadotrophin administration was shorter in the biosimilars group (WMD: -0.19 days, 95% CI: -0.34 to -0.05; I2 = 0%, 5 studies, n = 2081), while no difference was observed in the total dose of FSH (WMD: -34.69 IUs, 95% CI: -74.54 to 5.16; I2 = 15.53%, 5 studies, n = 2081). No difference was observed in the number of oocytes retrieved (WMD: 0.27, 95% CI: -0.43 to 0.96; I2 = 10.7%, 6 studies, n = 1527) and OHSS rates (RR: 1.17, 95% CI: 0.90-1.52; I2 = 0%, 8 studies, n = 2986) between the two groups. A significantly lower live birth rate was observed using the biosimilars of follitropin alfa compared to the originator in women undergoing ovarian stimulation for ART (RR: 0.83, 95% CI: 0.72-0.96; I2 = 0%, 6 studies, n = 2335; moderate certainty of evidence). Similarly, clinical pregnancy (RR: 0.82, 95% CI: 0.73-0.92; I2 = 0%, 7 studies, n = 2876; low certainty of evidence) and ongoing pregnancy rates (RR: 0.81, 95% CI: 0.70-0.94; I2 = 0%, 7 studies, n = 1886; low certainty of evidence) were lower in the biosimilars group. These results were not materially altered in the sensitivity analyses performed where studies deemed at high risk of bias were excluded.

LIMITATIONS, REASONS FOR CAUTION: This meta-analysis included RCTs evaluating seven different biosimilars of follitropin alfa; however, pooled data appeared to be homogeneous. No data were available comparing biosimilars of follitropin alfa with the originator regarding cumulative live birth rate per aspiration or the probability of live birth in frozen thawed cycles. The population examined in the eligible RCTs includes mainly normal responders and no RCTs were identified focusing on poor or high responders.

WIDER IMPLICATIONS OF THE FINDINGS: Clinicians should be informed that although biosimilars of follitropin alfa produce similar number of oocytes with the originator, pregnancy rates after a fresh transfer are likely to be lower. Future research should focus on optimizing the production and use of biosimilars of follitropin alfa, so that they lead to pregnancy rates comparable to the originator.

STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. K.I.K. and A.S. have no competing interest to disclose. E.M.K. reports personal fees and non-financial support from Merck, Ferring, IBSA, and Vianex. B.W.M. has been supported by an investigator grant from NHMRC, has received consulting fees from Organon, Merck, and Norgine, research support and non-financial support from Merck KGaA, Darmstadt, Germany. B.W.M. also reports having stocks from OBsEva. C.A.V. reports grants, personal fees, and non-financial support from Merck KGaA, Darmstadt, Germany, personal fees, and non-financial support from Merck, Sharpe and Dohme, personal fees and non-financial support from Organon, grants and non-financial support from Ferring, personal fees from IBSA, and personal fees and non-financial support from Gedeon Richter and Vianex.

REGISTRATION NUMBER: Protocol for the systematic review registered in The International Prospective Register of Systematic Reviews (PROSPERO; CRD42024498237).

PMID:39719046 | DOI:10.1093/humrep/deae274

Categories
Nevin Manimala Statistics

A pilot study of transcriptomic preimplantation genetic testing (PGT-T): towards a new step in embryo selection?

Hum Reprod. 2024 Dec 24:deae265. doi: 10.1093/humrep/deae265. Online ahead of print.

ABSTRACT

STUDY QUESTION: Is it possible to predict an euploid chromosomal constitution and identify a transcriptomic profile compatible with extended embryonic development from RNA sequencing (RNA-Seq) data?

SUMMARY ANSWER: It has been possible to obtain a karyotype comparable to preimplantation genetic testing for aneuploidy (PGT-A), in addition to a transcriptomic signature of embryos which might be suggestive of improved implantation capacity.

WHAT IS KNOWN ALREADY: Conventional assessment of embryo competence, based on morphology and morphokinetic, lacks knowledge of molecular aspects and faces controversy in predicting ploidy status. Understanding the embryonic transcriptome is crucial, as gene expression influences development and implantation. PGT has improved pregnancy rates, but problems persist when high-quality euploid embryos do not reach term. In fact, only around 50-60% implant, of which 10% result in miscarriage. Comprehensive approaches, including RNA-Seq, offer the potential to discover molecular markers of reproductive competence, and could theoretically be combined with extended-embryo culture platforms up to Day 14 that can be utilized as a proxy to study embryo development at post-implantation stages.

STUDY DESIGN, SIZE, DURATION: This prospective pilot cohort study was conducted from March 2023 to August 2023. A total of 30 vitrified human blastocysts with previous PGT-A diagnosis on Day 5 (D5) or Day 6 (D6) of development were analysed: n = 15 euploid and n = 15 aneuploid. Finally, 21 embryo samples were included in the study; the rest (n = 9) were excluded due to poor quality pre-sequencing data (n = 7) or highly discordant data (n = 2).

PARTICIPANTS/MATERIALS, SETTING, METHODS: Following warming and re-expansion, embryos underwent a second trophectoderm (TE) biopsy. The embryos were then cultured until day 11 to assess their development. Biopsy analysis by RNA-Seq, studied the differential expressed genes (DEG) to compare embryos which did not or did attach to the plate: unattached embryos (n = 12) versus attached embryos (n = 9). Thus, we also obtained a specific transcriptomic signature of embryos with a “theoretical” capacity for sustained implantation, based on plate attachment on day 11.

MAIN RESULTS AND THE ROLE OF CHANCE: The digital karyotype obtained by RNA-Seq showed good concordance with the earlier PGT-A data, with a sensitivity of 0.81, a specificity of 0.83, a Cohen’s Kappa of 0.66, and an area under the ROC of 0.9. At the gene level, 76 statistically significant DEGs were found in the comparison unattached versus attached embryos (Padj < 0.05; FC > 1). To address the functional implications of these differences, significantly deregulated pathways according to GO and KEGG categories were identified. The mural trophectoderm (TE) of the unattached blastocysts showed 63 significantly deregulated terms, displaying upregulation in autophagy, apoptosis, protein kinase and ubiquitin-like protein ligase activity, and downregulation of ribosome, spliceosome, kinetochore, segregation, and chromosome condensation processes. The overall transcriptomic signature specific to embryos still attached to the plate on day 11 (with a theoretically higher implantation capacity) consists of 501 genes, including: EMP2, AURKB, FOLR1, NOTCH3, LRP2, FZD5, MDH1, APOD, GPX8, COLEC12, HSPA1A, CMTM7, BEX3, which are related to implantation and embryonic development (raw P-value < 0.05; shrunk LFC > 1.1). These findings indicate that it might be possible to identify euploid embryos with a greater capacity for implantation and development, after excluding those embryos that present chromosomal alterations.

LIMITATIONS, REASONS FOR CAUTION: This study included a small sample size, remarkable variability between samples, and low success rate of RNA amplification. Also, structural chromosomal abnormalities were not included, and it was not possible to diagnose mosaic embryos. TE biopsy does not assure the chromosomal status of the whole embryo. The maximum day for in vitro development was Day 11, and attachment to the plate on this day does not provide a clear indication of implantation capacity and viability, which was not tested in this study.

WIDER IMPLICATIONS OF THE FINDINGS: The short-term goals following on from this pilot study is to expand the sample size with embryos of more complex abnormalities, and to perform a prospective in vitro preclinical validation. In a more distant future and with optimal results, this technique could have clinical application, thus increasing clinical outcomes by assessing both chromosomal content and transcriptomic profiling.

STUDY FUNDING/COMPETING INTEREST(S): The Institut Valencià de Competitivitat Empresarial (IVACE) (IMIDCA/2022/39) and Generalitat Valenciana (CIACIF/2021/11) supported the present study. A.C. is an employee of JUNO Genetics. He has received honoraria for an IBSA lecture and a Merck lecture. He is also a minor shareholder of IVIRMA Global. The other authors have no conflicts of interest to declare.

TRIAL REGISTRATION NUMBER: N/A.

PMID:39719045 | DOI:10.1093/humrep/deae265