Modern technologies in the assessment and treatment of pelvic organ prolapse - experimental and clinical studies

In this project, we aim to use modern assessment techniques to study certain risk factors related to the development of pelvic floor prolapse in a clinical setting as well as in an experimental model. Pelvic floor prolapse is a bothersome condition when the vaginal wall or the uterus protrudes through the vaginal opening. It affects mainly women who were at least once pregnant and delivered vaginally. The project includes clinical part during which we tried to contribute to the discussion on risk factors related to the development of pelvic organ prolapse and other pelvic floor dysfunctions. More extensive, experimental part, aimed to further characterize a large ovine animal model for the development of pelvic organ prolapse and for vaginal surgery.

The clinical study was conducted in Prague, Czech Republic, and included a large cohort of nulliparous women who delivered vaginally. One year after delivery one-third of women reported urinary incontinence, 13% had pelvic organ prolapse reaching the level of hymen or beyond and 3.3% reported some anorectal dysfunction mainly related to painful defecation. As a result of delivery, 18% of women sustained levator ani avulsion and 17% had levator hiatus ballooning. Both of which were tightly related to the current or future presence of pelvic organ prolapse and its recurrence after surgical correction. Demographic and obstetrical factors included age and body mass index increased the likely hood of urinary incontinence, age increases the risk for pelvic organ prolapse. Risk factors for levator ani avulsion included the forceps delivery, whereas epidural analgesia and perineal rupture grade I was decreasing.

Experimentally we worked with the sheep as a large animal model. First, we characterized the pelvic floor of the virgin ewe and compared it to that of women. Second, we documented the effects of certain key life time events such as first delivery, menopause and under its replacement therapy. We identified many anatomical and structural similarities such as vaginal dimensions, the composition of the vaginal wall, attachments of levator ani muscle. Some anatomical structures present in women are not developed in sheep (i.e. the sacrospinous ligament, internal obturator muscle and obturator membrane) and their pelvic floor anatomy is adapted to their quadruped position and presence of the tail. We observed the effect of specific life span factors (first vaginal delivery, ovariectomy, hormonal replacement therapy) on active and passive biomechanical properties of the ovine vagina. Following the first vaginal delivery, ovine vagina became more spacious, its distal part was less stiff and smooth muscles generated lower contractile forces. Following artificially induced menopause vagina was narrower and its middle part becomes stiffer. Estradiol hormonal replacement returned the stiffness in within the range of the premenopausal animal. Histology showed only a limited amount of changes and had not sufficiently explained observed changes in biomechanics.

The experimental work was dedicated to studying the effect of novel implants in the treatment of pelvic organ prolapse. In a comparative study, we used a bovine-derived acellular cross-linked collagen matrix (ACM) as an alternative to polypropylene flat meshes. Both types of implants were inserted in the ovine rectovaginal septum. After 6 months, ACMs showed more local graft-related complications and biomechanical properties comparable to polypropylene. Moreover, partial degradation of ACM had a negative impact on smooth muscle contractility. Due to theses observation, we concluded that ACM does not seem to have better biosafety profile than polypropylene.

To proceed with last experimental study in sheep we firstly need to further explore the potential and feasibility of arm anchored implant. In a small study, we performed a trocar guided transvaginal insertion of an H-shaped implant self-tailored to fit ovine anatomy and dimensions. No serious complications were identified therefore we used the technique for bigger prospective study. Moreover, the surgical procedure was recorded for educational purposes.

The subsequent study included previously described H-shaped mesh and flat mash, both fabricated from polymeric polyvinidylene fluoride loaded with iron particles that allow its visualization with magnetic resonance (MRI). In a longitudinal manner, we collected data documenting stable shape and position of implants. Initially, there was a drop in the effective surface area observed in both types of implants that remained stable until the end of the observational period. More detail analysis of thickness maps obtained from MRI data revealed two deformations patterns each of them specific for H-shape to flat mesh. Deformation of H-shaped implants was most probably related to distinct biomechanical properties of its central part and arms, whereas flat implants displayed heterogenic pattern most probably linked with pore aggregation caused with suturing. The polymer also showed a low rate of graft related complications, did not affect smooth muscle contractility yet increased the stiffness of augmented tissue.

In general, this project has shown that pelvic organ prolapse is linked with maternal age and delivery-related injuries. Up to every eight women may have a symptomatic prolapse already 1 year after her first delivery. Moreover, those with muscle injury are in higher risk of POP development in the future and its recurrence after the primary surgical repair. To improve our knowledge on POP development and treatment we further explored the potential of a large ovine model for prolapse and vaginal surgery. We showed that many anatomical and morphological features and vaginal wall changes induced by specific life span factors (first delivery, artificial menopause, hormonal replacement) are to a certain extent similar to observations in women. We further used this model for testing novel implants and visualization techniques. We believe that the ovine model should be used in future research of pelvic organ prolapse pathophysiology and novel treatment techniques.