Preimplantation genetic testing (PGT) is widely used in assisted reproduction to assess the genetic status of embryos. However, increasing evidence suggests that the trophectoderm (TE) may not fully reflect the genetic status of the inner cell mass (ICM), raising controversy about the accuracy of TE biopsy. Research in recent years has focused on cell-free DNA (cfDNA) found in blastocoel fluid (BF) and spent culture medium (SCM), as these may contain genetic information from both the TE and ICM. Therefore, further research and validation are essential to determine the reliability and clinical applicability of these diagnostic methods in PGT. Relevant studies published between January 2000 and August 2024 were identified through PubMed and Web of Science (WOS). Risk assessment and publication bias were evaluated using QUADAS-2 and Deek’s test. Diagnostic meta-analysis was performed using a bivariate model to combine sensitivity and specificity, with results visualized through forest plots and summary receiver operating characteristic (SROC) curves. Out of 6,407 initially screened records, 36 studies involving 4,230 embryos were included. TE biopsy was identified as the best method for diagnosing the genetic status of embryos (sensitivity: 0.839; specificity: 0.791, AUC: 0.878), while SCM had slightly lower accuracy (sensitivity: 0.874; specificity: 0.719, AUC: 0.869). The effectiveness of BF (AUC: 0.656) was significantly lower than that of TE biopsy and SCM. Despite this, TE biopsy has not yet achieved ideal diagnostic performance. However, TE biopsies demonstrate a high level of accuracy in diagnosing PGT-SR (AUC: 0.957). Additionally, multiple TE biopsies (AUC: 0.966) or TE biopsies combined with SCM (AUC: 0.927) can enhance the diagnostic efficiency of PGT. The findings of this study suggest that TE biopsy has yet to achieve optimal diagnostic accuracy, which may result in a significant number of missed embryo diagnoses and misdiagnoses. Our results confirm that SCM has the potential to serve as a supplementary test. Employing multiple biopsies or combining TE with SCM may enhance diagnostic efficiency and yield optimal results.

The clinical application of human stem cell-derived islet organoids (SC-islets) is hindered by immaturity and ischemia-induced dysfunction post-transplantation. Hypoxia-driven angiogenesis is a common adaptation, but the metabolic fragility of SC-islet β cells leads to early functional damage and suppressed vascular endothelial growth factor A (VEGFA) expression, thereby delaying vascularization and causing graft loss. The key challenge in SC-islet transplantation is how to prevent hypoxia-induced stress and promote rapid angiogenesis. We found that excessive zinc in SC-islet β cells induces oxidative modification that inhibits AMP-activated protein kinase (AMPK) activity. Chemical inhibition of zinc transportation activates AMPK, enhances functional maturation, improves hypoxia resistance, and increases hypoxia-inducible factor 1α (HIF1A)-independent VEGFA expression to facilitate endothelial cell integration. In diabetic animal models, this approach significantly improved hypoxia resistance, accelerated angiogenesis, and enhanced glycemic control. Our findings demonstrate that chemical inhibition of zinc transportation boosts SC-islet functional competence, offering a potential strategy to advance pre-adaptation to stress in regenerative medicine.

Recent studies have reported that embryos diagnosed as aneuploid by preimplantation genetic testing (PGT) can still result in successful live births after transfer. This suggests that, in addition to mosaic embryos, fully aneuploid embryos may also carry a risk of diagnostic error, potentially reducing the overall accuracy of PGT. Therefore, thoroughly investigating the risk and characteristics of aneuploidy misdiagnosis is crucial for optimizing PGT strategies and improving clinical outcomes in assisted reproductive technology (ART). Relevant studies published from January 2000 to December 2024 were identified through PubMed and Web of Science. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A diagnostic meta-analysis was conducted using a random-effects model to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs), combining sensitivity and specificity. Results were visualized using forest plots. A total of 22 studies were included to assess the discordance between trophectoderm (TE) biopsy and inner cell mass (ICM) or whole blastocyst (WB) results. The discordance rate for euploid embryo diagnosis was low (2.6%), whereas it was significantly higher for aneuploid embryos (9.2%). Segmental aneuploidies showed the highest discordance rate (17.4%). In the PGT-A population, misdiagnosis of segmental aneuploid embryos was particularly prominent (OR = 10.04, 95% CI: 7.60-13.27, I² = 0%, P < 0.001). The results indicate that embryos with segmental aneuploidies have a significantly higher risk of misdiagnosis, especially in the PGT-A population. This highlights the need for caution when interpreting trophectoderm (TE) biopsy results involving segmental aneuploidies, to avoid misdiagnosis and the inadvertent discard of potentially viable embryos.

Optimal endometrial thickness and receptivity, precisely regulated by steroid hormones, are critical determinants for successful embryo implantation. Thin endometrium is a major cause of female infertility, yet its pathogenesis requires further exploration. Cellular proliferation and differentiation are highly dependent on the activation status of intracellular metabolic signaling pathways, among which the mammalian target of rapamycin (mTOR) signaling pathway serves as a central metabolic integrator. However, the mechanistic links between mTOR dysregulation, metabolic reprogramming, and endometrial regenerative failure remain poorly understood, representing a critical knowledge gap in reproductive medicine. Uterine-specific Raptor knockout mice (Rptor^fl/flPgr^cre/+) were generated using the Cre-LoxP system. Endometrial pathology was assessed through multi-dimensional analyses: (1) hematoxylin–eosin staining, immunofluorescence, and T2-weighted magnetic resonance imaging were used to quantify endometrial dimensions, glandular development, and vascularization; (2) Functional competence was evaluated via the Pollard experiment and artificial decidualization models to assess receptivity and decidualization; (3) Molecular mechanisms were dissected using high-throughput RNA sequencing and flow cytometry to profile mTORC1-mediated cholesterol synthesis signaling, endometrial renewal, and cell cycle progression. Rptor^fl/flPgr^cre/+ mice recapitulated key features of thin endometrium syndrome, exhibiting significantly reduced endometrial thickness, impaired glandular development, and defective vascularization. Despite having comparable estrogen and progesterone levels, these mice displayed profound endometrial receptivity defects and impaired decidual response. Raptor deficiency attenuated cell proliferation by disrupting lipid metabolism pathways, consequently impairing estrogen responsiveness and diminishing uterine regenerative capacity. Our study establishes that mTORC1 signaling orchestrates hormone-responsive endometrial proliferation through metabolic regulation, fundamentally underpinning endometrial receptivity and decidualization. These findings provide mechanistic insights into the pathogenesis of thin endometrium and highlight potential therapeutic targets for infertility treatment. The online version contains supplementary material available at 10.1186/s11658-026-00888-x.