Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
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PloS one
Distinct endometrial protein profiles in spontaneous and stimulated cycles in women with poor ovarian response: A prospective case-crossover clinical trial
The window of implantation is a critical period for embryo implantation. Ovarian stimulation can disrupt endometrial receptivity, potentially through altered gene expression and downstream protein profiles. However, the impact on the endometrial proteome remains underexplored. Identifying biomarkers of endometrial receptivity may provide an opportunity to develop targeted interventions aimed at improving implantation outcomes. This prospective, case-crossover, open-label study was conducted at the Department of Human Reproduction, Division of Obstetrics and Gynecology, University Medical Centre Ljubljana, Slovenia, from September 2023 to June 2024. The study included 15 women aged <43 years with primary infertility and poor ovarian response. Endometrial samples were collected using a pipelle biopsy during the window of implantation in spontaneous and stimulated cycles and analyzed using protein microarrays targeting 1,466 proteins. Differential protein abundance was assessed using a multi-factorial linear model, including patient-specific effects as an additional factor to account for the paired case-crossover design. Effect sizes are reported as log2-fold changes with corresponding 95% confidence intervals. Differential abundance was defined a priori as |log2FC| > 0.5 with FDR-adjusted p-value < 0.05. Comparison of endometrial samples from spontaneous and stimulated cycles revealed 114 antibodies with differential abundance. Key proteins were associated with immune response (IL-8, proteins S100-A8 and S100-A9, CAMP) and extracellular matrix remodeling (MMP-9). Exploratory KEGG pathway mapping suggested involvement of immune and inflammatory pathways, including cytokine-cytokine receptor interaction and IL-17 signaling. Cluster analysis demonstrated distinct proteomic patterns, with all stimulated-cycle samples showing alterations and a subset of stimulated-cycle samples (40%) exhibiting more pronounced changes. The findings indicate that ovarian stimulation is associated with measurable alterations in the endometrial proteomic profile during the window of implantation. These changes may be relevant to biological pathways involved in endometrial receptivity and implantation. Further studies in larger cohorts are needed to validate the identified candidate markers and determine their clinical relevance for implantation outcomes. Trial registration: ClinicalTrials.gov NCT06804174.
22 May 2026
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Misdiagnosis of different types of aneuploidy in preimplantation genetic testing (PGT): a systematic review and meta-analysis
PURPOSE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.
8 Apr 2026
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