Describing how our group functions can best be demonstrated by summarizing the insights we have made over the last decade and showing how they arose from interaction between the disciplines of biomechanical engineering, anatomy, clinical mechanisms research and clinical trials.
Basic science insight leads to a more complete understanding of the clinical disease stress urinary incontinence. We used the engineering technique of system input, system output analysis of 1000 Hz recordings from the urethra and bladder during cough and valsalva in 30 volunteers to analyze the pressure dynamics that occurred during increases in abdominal pressure. This research identified the clinical relationship between resting urethral closure pressure, the transmission of abdominal pressure to the urethra during a cough, and the pressure at which leakage would occur. This insight demonstrated that incontinence could not be understood by either pressure transmission or resting urethral function alone. It also highlighted the need to understand the anatomical and physiologic derangements responsible for changes in these parameters.
MRI allows the continence mechanism and pelvic floor anatomy to be directly visualized
Advanced clinical imaging allows scientific study of the pelvic floor structures. The anatomical basis for magnetic resonance imaging of the pelvic floor was established by performing magnetic resonance scans of cadaver material and then making anatomical sections of the same cadavers in the same planes for direct macroscopic and microscopic examination. Studies using pattern-matching techniques in whole pelvis and histological cross sections of pelvic floor tissues demonstrated the ability to visualize the urethra and levator ani muscles involved in continence. This allowed the integrity of individual components to be studied objectively and compared between normal and symptomatic women. In this way, the site of individual defects could be demonstrated. The normal appearance of the pelvic floor in nulliparous volunteers was then studied in 80 nulliparous volunteers with proven continence and normal pelvic floors quantified to form the basis for research into the changes that occur during vaginal birth and with the development of pelvic organ prolapse.
Relationship between structure and function
Biomechanics guides clinical testing, leading to improved understanding of the nature of women’s problems. The vesicourethral pressuregram demonstrated that understanding continence required the assessment of both static urethral closure pressure and the dynamic function of the vesical neck supports. It indicated that clinical tests needed to be devised that would assess the structure and function of each element of the system. To do this, we designed and made an instrumented vaginal speculum that quantified force generated by the levator ani. In addition, we developed a strategy for quantifying the stiffness of the urethral supports using ultrasound rather than X-ray so that studies could ethically be carried out in symptomatic women and normal controls. This permitted study of the standard Valsalva maneuver, and, because the ultrasound image can be evaluated frame-by-frame, study of the rapid movements during a cough are also possible. These assessments led to clinical insights. In studying 17 nulliparous and 18 continent primiparas and comparing them with 23 incontinent primiparaous women, we discovered that loss of urethral support during a cough was different than loss of support during Valsalva maneuver performed with the levator ani muscles relaxed. Primiparous and nulliparous incontinent women had differences of 4.6 and 4.2 mm respectively, while the incontinent women had a difference of only 1 mm. This research identified the important role that the state of the levator ani muscles plays in urethral support. When the standard clinical test of assessment of vesical neck movement during a valsalva was performed, there was no difference between the controls and the incontinent women.
New mechanism insights led to changes in clinical treatment
Identification of the role of the levator muscle in urethral support stimulated our interest in evaluating the way in which the muscle participated in maintaining continence. In questioning women who were successful with pelvic muscle training for SUI, we discovered that continence improved in some women immediately, long before muscle strengthening could occur. This suggested that proper timing of muscle contraction was important to stiffen the urethral supports. Teaching women when to contract at the moment of a cough might improve continence as much or more than trying to build muscle strength. The research concerning teaching the women the “knack” of proper muscle timing demonstrated that selected older women with SUI could reduce urine loss during a cough (by 73%) within one week. We followed this up by demonstrating that muscle contraction did decrease urethral excursion from 5.4 to 2.9 mm by activation of the levator ani muscle.
Vaginal birth identified as the source of levator ani muscle damage
The fact that muscle action plays an important role in supporting the urethra and preventing urinary incontinence raises the following question: what damages the muscle to prevent its normal function? Dr. Sampselle’s randomized trial on pelvic muscle exercise as a preventative measure for urinary incontinence in 46 women used the instrumented vaginal speculum developed by Biomechanical Engineering. The study revealed a loss of muscle function after delivery in both the control group and the intervention group, suggesting that vaginal birth influences the levator ani muscle. It was subsequently demonstrated that the levator ani muscle could be evaluated after delivery on MR scans, and a project was funded to compare stress incontinent primiparous women with continent nulliparas and primiparas. MR images in 80 women from each of these three groups demonstrated, for the first time, that the levator ani muscle damage is seen in 20% (32/160) of primiparous women, and not at all in nulliparas.
Is the levator ani muscle important to just stress incontinence, or also to other pelvic floor disorders?
The pressuregram indicated that urethral function should also play a role in incontinence and suggested the need for a clinical testing strategy that looks not at any one factor to cause incontinence, but to a combination of problems. This has been documented by the development of a systematic, item-by-item examination of the sphincter and the support. Our completed study of continent and incontinent women after vaginal delivery tested the null hypothesis that incontinence can be defined by either sphincter function or support stiffness alone. Our initial data presented in Project 2 preliminary studies disproves this hypothesis and indicates that at least these two factors play a role in causing the pre-clinical disease seen after vaginal birth. The relationship between this mild subclinical disease and the full-blown problem that leads women to seek care later in life is yet to be explored. Furthermore, in the first 80 women in our study of pelvic organ prolapse and the levator ani, we have seen that major muscle injuries are seen in 68% of women with pelvic organ prolapse, but only 24% of age and parity matched controls.
Quantification of urethral striated muscle cells leads to new insights concerning the nature of sphincter deterioration
The pressuregram’s suggestion that urethral function played a role and the clinical demonstration of its importance raised the question concerning the mechanism of sphincter dysfunction. Histological analysis of 33 urethrae across the lifespan demonstrates systematic loss of striated muscle cells associated with a concomitant loss of neural tissue. There is a dramatic difference between the 35,000 muscle fibers seen in young women’s urethrae and the revelation that some 70-year-old women have as few as 5,000. This loss is not uniform, but is most significant near the vesical neck and on the vaginal side of the urethra. These early observations need follow-up to help point toward basic science research into the cellular and molecular mechanisms responsible for loss of muscle and the developmental factors that lead to formation of a normal muscle mass. For example, are there women born with a vulnerable urethra with few fibers, and what events during vaginal birth denervate the urethra to lead to loss of function?