Pelvic floor dysfunction resulting in disorders such as pelvic organ prolapse (POP) and stress urinary incontinence (SUI), are considerable problems among women and adversely affect the quality of life. The pelvic floor refers to the whole structure that supports and provides positioning for the pelvic organs like the bladder, uterus and rectum. It is a fibromuscular structure comprising of striated muscles (i.e. levator ani muscle), smooth muscles, nerves, ligaments and connective tissue attachments between the vagina and pelvic side wall. POP is defined as the descent of one or more pelvic organs into the vaginal canal. Its prevalence is about 40% in women over 45 years of age, up to 50% in parous women. The lifetime risk of undergoing pelvic floor surgery is estimated to be about 11–20%, with a cumulative incidence increasing by age (20.3% in age group 76-85 in the Netherlands). Moreover, the failure rate of this surgery is high, with 30% of women requiring reoperation.
The aetiology of POP is multifactorial, with vaginal delivery considered as the major risk factor, as well as obesity, age, and menopause as other common risk factors. During vaginal delivery severe trauma to the soft tissues of the pelvic floor occurs since the tissues are compressed, stretched, injured and can become hypoxic. However, the exact mechanisms of this injury and intrinsic tissue properties influencing the development of pelvic floor dysfunction, are still largely unknown.
Studies have shown that the biomechanical properties of the human vagina wall in POP tissue significantly differ from non-POP tissue, i.e. POP vaginal tissue is associated with increased stiffness and failure stress and a decreased strain at failure. A drawback of those studies is the lack of standardisation. Different experiment protocols and analysis models are used, making those results incomparable. Moreover, current studies use uniaxial stress/strain testing, whereas the anisotropic vaginal wall connective tissue is best tested under biaxial testing conditions.
Increasing age, vaginal childbirth and obesity are well-identified risk factors for POP. In The Netherlands, the total prevalence of women with overweight was 42% in 2012, with 12% having obesity. The connective tissue properties of the vaginal wall change with age and become less elastic while stiffness increases. Several studies relate obesity to a decrease in elastin concentration or alterations in the composition and organization of collagen in connective tissue. Also a correlation with lysyl oxidase (LOX) down regulation is found, causing elastin fibre fragmentation, defective maturation of fibroblasts and tissue remodeling resulting in a higher stiffness. Excessive mechanical loads can interfere with normal cellular gene expression and cause connective tissue disease. Consequently, structural tissue remodelling occurs, causing further tissue deterioration and impaired biomechanical behaviour. Recently it was shown that vaginal wall tissue properties of POP women with a BMI>25 have higher tangent moduli, strain-energy densities and yield and failure stresses on uniaxial testing, and therefore are stiffer and tougher compared to women with a BMI<25.
Focus of this study
The aim of the study is to assess structure-function properties of vaginal wall tissue of women with a POP, where mechanical properties obtained from biaxial testing experiments are correlated to tissue composition (using biochemical assays to quantify DNA, collagen, elastin and GAGs) and structural organisation (using collagen imaging and image analysis). Since there is ample access to human tissue material, associations between tissue behavior and age, parity, BMI, smoking, and POP Stage and localization (anterior or posterior vaginal wall) can be part of the study protocol.