Embryo-derived extracellular vesicles and their potential as biomarkers for embryo quality during IVF: a systematic...

Over the past decade, extracellular vesicles (EVs) released from embryos have received increasing attention for their potential role in influencing embryo-maternal communication events during implantation. Several studies have explored the relationship between embryo-derived EVs and embryo developmental competence. To synthesize current insights, we conducted a systematic review of the literature, highlighting key findings and evaluating how embryo EV profiles relate to embryo developmental competence.

A systematic review was conducted in accordance with the PRISMA guidelines. The review intended to (i) synthesize the existing knowledge on embryo-derived EV concentration, size, and cargo and their association with embryo developmental competence in mammalian systems, (ii) propose recommendations for future research, and (iii) assess the potential impact of the current literature on embryo selection during IVF.

A literature search was performed across five databases (MEDLINE, EMBASE, BIOSIS Previews, Web of Science, and Scopus), involving keywords 'Embryo' AND 'Extracellular vesicle'; many synonyms were included for each keyword along with map terms when available. The search was conducted on 14 January 2026. References were screened for additional relevant records. Abstract-only authors were contacted to determine whether full-text was available. The inclusion criteria were 'collection of culture media from embryos of any mammalian species and isolation and assessment of EVs from it'. Reasons for exclusion included: 'No collection of embryo culture media', 'No characterisation or assessment of EVs', 'Not embryo-derived EVs', and 'Review/Theory/Lacking primary data'.

Our searches collected a total of 15 620 records; of these, 32 studies from 34 records were included in the systematic review. The included studies were divided into two groups: (i) studies of embryonic EV characteristics and (ii) studies that investigated the association of embryonic EV characteristics and embryo developmental competence, including embryo quality assessments based on morphology, ploidy, and pregnancy. Wide variations in embryo EV concentration and size were reported, largely due to differences in study designs. Overall, the quality of the existing literature ranged from low to moderate quality. Among the three human and eight bovine studies that examined the association of embryo EV concentration, size, and/or cargo with developmental competence, the certainty of the evidence for all outcomes was consistently very low. Studies often reported opposing directions of effects, whilst others showed no clear association. Inconsistencies in EV isolation techniques, timing of EV sampling, and methods for embryo quality assessments complicate efforts to assess whether embryonic EVs can be used as a reliable biomarker.

Current evidence does not support the use of embryo EVs as biomarkers during IVF procedures. To enhance reproducibility and the production of high-quality studies, it is recommended that studies incorporate standardized approaches to EV isolation and characterization to align with best practices. In addition, the timing of EV sampling should be standardized, appropriate media controls used, and optimal measures of developmental competence, such as live birth, reported. Adherence to these recommendations will enable future studies to build constructively on the existing literature, with the possibility of informing clinical applications that improve patient outcomes.

https://doi.org/10.17605/OSF.IO/TPXVU.