P-453 Non-autologous human platelet lysate as a therapy for recurrent implantation failure: lessons from in vitro models
Bibliographic record
Abstract
Abstract Study question Which biological pathways are modulated by primary human endometrial cells in response to in vitro treatment with non-autologous human platelet lysate (HPL)? Summary answer HPL treatment stimulates endometrial growth and trophoblast attachment by activating cell proliferation, and modulating cell-cell signaling and extracellular matrix organization. What is known already Inadequate endometrial receptivity and a thin endometrium (TE) are contributing factors to recurrent implantation failure (RIF), which occurs in 10% of in vitro fertilization cycles. Studies have reported that autologous platelet-rich plasma stimulates endometrial growth and enhances receptivity, thereby improving implantation rate in RIF patients. We previously showed that non-autologous human platelet lysate (HPL) promotes in vitro proliferation of primary endometrial epithelial (EECs) and stromal cells (ESCs). Our data suggest that HPL may standardize and improve future clinical treatments for a TE and endometrial origins of RIF. Study design, size, duration Endometrial tissue was collected from five proliferative phase control and eighteen RIF patients at the CReATe Fertility Centre, Toronto, Canada. The RIF patients were separated into three groups (N = 6 each): 1) proliferative phase RIF, 2) secretory phase RIF, and 3) secretory phase RIF+TE. Primary EECs and ESCs were enzymatically isolated, cultured separately, and treated with either serum-free media (SFM), or SFM + 1% HPL (EECs), or 10% HPL (ESCs). Participants/materials, setting, methods Cell proliferation was assessed using PrestoBlueTM reagent and immunocytochemistry for Ki67. Pooled RNA libraries were prepared and sequenced for 150 cycles paired-end. Differential expression was performed using DESeq2 and pathway analysis with Enrichr. Using an in vitro model of embryo attachment, attachment between HTR-8/SVneo trophoblast spheroids and EECs was assessed by fluorescent microscopy and ImageJ™ software. Main results and the role of chance For all groups, 48-hour treatment with non-autologous HPL stimulates a significant increase (1.24-1.49-fold, P<0.05) in EEC proliferation. Whereas ESCs experienced a significant 1.29-fold and 1.92-fold increase (P<0.05) in proliferation for proliferative phase RIF and secretory phase RIF+TE respectively. HPL-treated EECs also exhibited significantly increased attachment to HTR-8 spheroids from 57.52% to 86.5% (P<0.01) in RIF+TE cultures and 42.58% to 68.90% (P<0.01) in RIF only cultures. Comparing SFM vs. HPL treatment identified 45 significantly upregulated (log2FoldChange >2 and padj <0.05) genes, including MMP1 and MMP9, and 30 significantly downregulated genes including KL and ADRA2A. Whereas ESCs had 429 significantly upregulated genes, including BUB1 and PLK1, and 378 significantly downregulated genes, including PTGIS and ADAMTS16. Upregulated pathways included extracellular matrix organization and mitotic cell cycle. Downregulated pathways included NOTCH1 signaling and synthesis of prostaglandins. Limitations, reasons for caution Our data suggests in vitro HPL treatment significantly stimulates endometrial cell proliferation, trophoblast attachment, and modulates receptivity. However, the small sample size per group (N = 6) underscores the need for larger samples and randomized controlled trials to establish the clinical efficacy of HPL as a treatment for endometrial origins of RIF. Wider implications of the findings HPL treatment for RIF and TE is gaining global acceptance by fertility clinics. Our study establishes the molecular groundwork to understand how HPL impacts endometrial growth and receptivity, offering mechanistic insights into this therapeutic approach and informing future treatments aimed at enhancing the success of embryo transfers. Trial registration number not applicable
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".