959: Molecular characterization of the post cesarean uterine scar

Abstract

Cesarean section (CS) accounts for 31.9% of births in the United States and is associated with a 3.6-fold increase in maternal mortality, in part due to complications in future pregnancies such as uterine rupture or placenta accreta. CS technique is largely anecdotal because it is not known how the unique structure of the uterus nor CS surgical factors impact scar formation. The purpose of this study was to investigate the histologic structure and density of post-CS uterine scar. Lower uterine segment was prospectively biopsied at the time of repeat CS (n=4). Samples from a primary CS and premenopausal non-pregnant hysterectomy specimen were used for comparison. Data collected included demographic information and inter-conception interval (ICI). Biopsy specimens were formalin fixed, paraffin embedded, and sections were stained with Masson Trichome to differentiate collagen (blue) and myometrium (red/purple). Representative images were analyzed using ImageJ software. Collagen bundle thickness was quantified, and ANOVA was used to detect differences between samples. Tissue specimens were sent for 3- dimensional molecular imaging with MicroCT. Vivoquant software was used for segmentation analysis of MicroCT images. Differences in tissue density were compared using Chi-square, with significance at p<0.05. Collagen bundles were thicker and more disorganized in subjects undergoing repeat CS compared to unscarred pregnant and post-menopausal specimens (p < 0.001). The range of collagen bundle size was also wider in subjects with a shorter 29-34 month ICI compared to a longer 106-108 month ICI (2.37-23.84 mm vs 2.37-9.00 mm). MicroCT analysis revealed a heterogeneous distribution of scar density within RCS tissue samples (p < 0.001), with collagen density randomly distributed between serosal and endometrial surfaces. Post-CS scar structure is characterized by increased collagen bundle thickness compared to native uterine tissue. Scar structure is dynamic over time with more abundant and disorganized collagen bundles present earlier in the healing process, and more contracted scar over time. MicroCT analysis shows heterogeneity in scar density, even among samples of similar ICI, suggesting the importance of individual variation. Further study is needed to determine if molecular characteristics of uterine scar structure are associated with adverse pregnancy outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)