Orlicky DJ, Guess MK, Bales ES, et al. - Researchers aimed at comparing women with and without prolapse using the novel, Pelvic Organ Prolapse Histologic Quantification System for uterosacral ligament histologic features. In addition, they examined if composite histologic findings in uterosacral ligaments are linked with prolapse risk factors. In this prospective, cohort study, paracervical uterosacral ligament biopsies were conducted at the time of hysterectomy for primary prolapse or other benign gynecologic indications and were processed for histologic evaluation. Analysis was performed on the histologic scores of 81 prolapse and 33 control ligaments. Unbiased principal component analysis of the histologic scores led to the stratification of the prolapse ligaments into three phenotypes: 1) raised adipose accumulation, 2) raised inflammation and 3) abnormal vasculature, with variable overlap with controls. Posthoc analysis of these subgroups established a positive association between increasing number of vaginal deliveries and BMI with raising adipose content in those of the adipocyte accumulation and inflammatory phenotype, and raised neointimal hyperplasia in the vascular phenotype. However, in the adipose phenotype, only the correlation between vaginal delivery and adipocytes was significant. These findings are suggestive of the existence of histologic phenotypes in pelvic support ligaments that can be differentiated utilizing the Pelvic Organ Prolapse Histologic Quantification System and principle component analysis. They support pelvic organ prolapse to have a multifactorial etiology contributing to altered smooth muscle, vasculature, and connective tissue content in crucial pelvic support structures.