Tubal occlusion in patients with hydrosalpinx modifies the uterine environment and improves in vitro fertilization outcomes within 7 months.

PURPOSE: Hydrosalpinx reduces the pregnancy outcomes of in vitro fertilization and embryo transfer (IVF-ET). Tubal occlusion has been shown to improve IVF-ET success; however, the optimal timing of oocyte retrieval and the molecular changes following tubal occlusion remain unclear.

METHODS

Retrospective and prospective cohorts of patients with hydrosalpinx were analyzed. Logistic regression, piecewise regression, and mediation effect analyses were used to identify the optimal timing of oocyte retrieval and the impact of tubal occlusion on pregnancy outcomes. Bulk and single-cell RNA sequencing (RNAseq) were applied to investigate potential molecular changes underlying these effects.

RESULTS

In total, 976 patients with hydrosalpinx were included. Logistic regression showed that delayed oocyte retrieval after occlusion significantly reduced clinical pregnancy (multivariate-adjusted: odds ratio [OR] = 0.904, P = 0.001) and live birth (multivariate-adjusted: OR = 0.926, P = 0.010). Curve estimation and piecewise regression indicated improved pregnancy outcomes within 7 months after occlusion. These findings were consistent regardless of baseline hormone levels or ovarian reserve. Endometrial RNAseq revealed activation of immune-related pathways before occlusion-including human T-cell leukemia virus 1 infection, natural killer cell-mediated cytotoxicity, cellular senescence, antigen processing and presentation, and complement and coagulation cascades-that were inactivated after occlusion, alongside upregulation of CXCL14 expression. CIBERSORTx identified a higher proportion of T follicular helper cells before occlusion (P = 0.02) and increased M2 macrophage infiltration after occlusion (P = 0.029), which was confirmed by CD163 immunohistochemistry. Finally, single-cell RNAseq suggested that CXCL14 expression in endometrial epithelial cells may interact with macrophages to promote M2 polarization, fostering a low-inflammatory microenvironment favorable for IVF-ET outcomes.

CONCLUSION

This study demonstrates that oocyte retrieval within 7 months after tubal occlusion is optimal for patients with hydrosalpinx, potentially due to CXCL14-mediated modulation of the endometrial immune microenvironment.