Yuki Mikami

CLINICAL VALUE OF PREOPERATIVE URODYNAMIC EVALUATION IN FEMALE PELVIC ORGAN PROLAPSE

INTRODUCTION AND OBJECTIVES: Pregnancy and childbirth are risk factors for female pelvic floor dysfunction (FPFD), yet it is unclear whether this is due to the effects of pregnancy, delivery, or both. Mice lacking the protein Lysyl Oxidase Like-1 (LOXL1 KO) have abnormal elastic fiber homeostasis and frequently develop FPFD after vaginal delivery. Our objective was to test the hypothesis that tissue changes resulting from vaginal delivery lead to FPFD as a result of abnormal elastic fiber homeostasis in this mouse model. METHODS: Age-matched primigravid female LOXL1 KO mice were allowed to have a spontaneous vaginal delivery (SVD) at term or were delivered by cesarean section (CS) at 20 days gestation. After delivery, mice were observed weekly for the development of POP using the Mouse Pelvic Organ Prolapse Quantification (MOPQ) system. Kaplan-Meier curves were created to describe the development of POP. At 12 weeks post-partum, lower urinary tract function was assessed by conscious cystometry (CMG) and leak point pressure (LPP) testing. Statistical analysis was performed with the Kruskall-Wallis test. Urethrovaginal cross-sections were stained for elastin and analyzed using a histological grading scale to assess elastin fiber disorganization and fragmentation. RESULTS: 39 mice were delivered by SVD and 36 delivered by CS. 12 weeks after SVD or CS, 23 (59%) and 11 (31%) mice had developed POP, respectively. The mean time to develop POP was 7.2 weeks after SVD and 10.5 weeks after CS (log rank, p=0.0008). Mice with POP had a significant increase in rate of non-void bladder contractions during CMG (p=0.02). Neither POP, nor route of delivery, were associated with differences in voided volume, voiding pressure, voiding time or leak point pressure. POP, but not mode of delivery, was associated with a significant increase in disorganization and fragmentation of elastic fibers. CONCLUSIONS: CS delays, but does not prevent, the development of POP when compared to SVD in LOXL1 KO mice. POP is associated with increased bladder contraction frequency and increased elastic fiber fragmentation and disorganization in the urethra and vagina. SVD leads to an increased incidence of POP in the setting of abnormal elastic fiber homeostasis.