Translation and validation of the international consultation on incontinence questionnaire-Bowel in Danish men and women with pelvic floor disorders.

BACKGROUND: We lack a comprehensive validated Danish questionnaire to evaluate symptoms and bother regarding anal incontinence (AI). The International Consultation on Incontinence Questionnaire-Bowel (ICIQ-B) is an internationally recommended questionnaire containing 21 items, of which 17 are scored in three subscales: bowel pattern, bowel control, and quality of life. AIMS: To translate the ICIQ-B into Danish and to validate the Danish version in pelvic floor disorder (PFD) patients with and without AI. METHODS: The ICIQ-B was translated by a panel of healthcare professionals followed by cognitive interviews with PFD patients attending an outpatient clinic. Revisions were undertaken using an iterative process, and a backward translation was performed for the final version. Pretesting and test-retest of the ICIQ-B were done online and administrated together with the St. Mark's score. Content, structural, convergent and discriminant validity were assessed, followed by an evaluation of relative and absolute reliability, including the smallest real difference (SRD). RESULTS: Thirty cognitive patient interviews were performed, resulting in three revisions. The Danish ICIQ-B was found to be comprehensible and relevant but lacked items addressing the psychological impact of bowel problems. The ICIQ-B was completed online by 227 PFD patients with and without AI. The structural validity of the bowel pattern subscale could not be retrieved. Patients indicating AI had significantly higher ICIQ-B and St. Mark's scores than patients without AI, and ICIQ-B subscale scores correlated moderately with St. Mark's scores. Internal consistency was good except for the bowel pattern subscale. Seventy-six patients completed test-retest. Relative reliability was excellent for subscale scores and moderate or good for single items except for the item concerning stool consistency, which was weak. The SRD was found to be 2.8 for the bowel pattern subscale, 4.3 for bowel control subscale, and 3.6 for the quality-of-life subscale. CONCLUSION: The Danish version of the ICIQ-B can be used for Danish patients with PFD, and discriminant validity is good. The structural validity and the internal consistency of the bowel pattern subscale are questionable, indicating that some items do not represent the underlying construct. Test-retest reliability of the ICIQ-B is acceptable, but the change needed to reflect a real change above the measurement error in each subscale is three to four points.

Perineal resuturing versus conservative treatment for dehisced perineal wounds and episiotomies: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: Perineal wound dehiscence is associated with complications, such as infections, perineal pain, dyspareunia, and altered sexual function, that severely affects women's health. Currently, few studies have examined secondary repair of first- and second-degree perineal wound dehiscence and episiotomies, and there is currently no consensus on the optimal treatment option for dehisced perineal wounds. The objective was to evaluate whether resuturing or conservative treatment of first- and second-degree dehisced perineal wounds and episiotomies is the optimal treatment modality in terms of postoperative healing time and other secondary outcomes. METHODS: A systematic literature search was carried out using PubMed, Embase, and Cochrane databases. All included studies were evaluated using the SIGN methodology checklist, with the purpose of assessing the study quality. RESULTS: Three randomized controlled trials were included. Only two small sample-sized studies presented data regarding healing time for both the resuturing and the conservative treatment groups. However, no significant difference was found between the two groups at 4-6 weeks' healing time (RR 1.16, 95% CI 0.53-2.52). One study found that women being resutured experienced a significantly reduced healing time and higher satisfaction with the appearance of the wound healing at 3 months compared with the conservative treatment group. CONCLUSION: We found no significant differences in the healing time between the resuturing group and the conservative treatment group. However, the sample sizes of the studies were small. A well-designed, large, and prospective randomized controlled trial is needed to evaluate the optimal treatment modality for dehisced perineal wounds.

Increased risk of obstetric anal sphincter injury in women undergoing vaginal delivery after caesarean section: A systematic review and meta-analysis.

BACKGROUND: There is increased focus on obstetric anal sphincter injury (OASI) and there are several well-established risk factors such as birthweight, instrumental delivery and median episiotomy. Some studies have found increased risk of OASI in women delivering vaginally after a previous caesarean section (VBAC). OBJECTIVE: To evaluate whether there is increased prevalence of OASI in VBAC compared with primiparous women. SEARCH STRATEGY: Literature search using PubMed, Embase and Cochrane databases. SELECTION CRITERIA: All studies with data on both primiparous women and women undergoing VBAC were included. All included studies were evaluated using the "SIGN - methodology checklist" to verify if the quality was acceptable. DATA COLLECTION AND ANALYSIS: This systematic review included 23 articles conducted in 11 countries over 19 years. Included studies were analysed using RevMan version 5.4. MAIN RESULTS: We found increased prevalence of OASI in the VBAC group; 8.18% (95% confidence interval [CI] 8.07-8.29) compared with 6.59% (95% CI 6.56-6.62) in primiparous women. Correspondingly, the meta-analysis revealed increased prevalence for OASI in the VBAC group (odds ratio 1.27, 95% CI 1.10-1.47). We found a high level of heterogeneity (I2  = 98%). CONCLUSION: Women undergoing VBAC had a higher prevalence of OASI compared with primiparous women.

Wexner score and quality of life in women with obstetric anal sphincter injury.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injury causes anal incontinence in half of the women affected. However, most symptoms are mild. The objective of this study was to evaluate the prevalence of anal incontinence and quality of life in women at long term after delivery with obstetric anal sphincter injury. We also wanted to identify a relevant cutoff level of the Wexner score (also known as the Cleveland Clinic Incontinence Score) to indicate affected quality of life in these women. METHODS: We performed a population-based questionnaire cohort study with prospective follow-up, including all women in Denmark with obstetric anal sphincter injury and one subsequent delivery between 1997 and 2005. We performed uni- and multivariate analyses and calculated the area under the ROC curve. RESULTS: In Denmark, 3885 women had an obstetric anal sphincter injury in their first delivery and a second delivery between 1997 and 2005 and no subsequent deliveries until 2010-2011. Questionnaires were sent to 3259 eligible women, and the response rate was 74.6%. In total, 2004 women could be included in the final analyses. Of these, 29.2% (n = 584) reported affected quality of life due to anal incontinence at long-term follow-up. We found that all symptoms of anal incontinence were associated with affected quality of life. The median age at follow-up was 40.3 years. The area under the ROC curve was 0.96 (95% CI 0.95-0.97) with a sensitivity of 0.94 (95% CI 0.92-0.96) and a specificity of 0.85 (95% CI 0.84-0.87) corresponding to an optimal cutoff level of the Wexner score of ≥ 2 to identify women with affected quality of life due to anal incontinence. CONCLUSIONS: In women with obstetric anal sphincter injury, 29% reported affected quality of life due to anal incontinence at long-term follow-up, and we found a low Wexner score cutoff level of ≥ 2 to identify women with affected quality of life.

Changing incidence of obstetric anal sphincter injuries-A result of formal prevention programs?

INTRODUCTION: Obstetric anal sphincter injuries (OASIS) are serious complications to vaginal delivery causing anal incontinence in 50% of the women in the long term. In Norway, the incidence of OASIS has been significantly reduced from 4%-5% to 1%-2% after implementation of prevention programs focusing on perineal protection. The aim of our study was to evaluate whether implementation of formal prevention programs was associated with a reduced incidence of OASIS over time. MATERIAL AND METHODS: We performed a historical cohort study, evaluating incidence, change of incidence and risk factors of OASIS during the years 2011-2015 at the four delivery departments in the Capital Region of Denmark. Two of the four departments implemented formal prevention programs in 2012-2013. We performed trend tests and uni- and multivariable analyses, adjusting for important risk factors and calculating interactions between risk factors. RESULTS: There were 75 173 vaginal deliveries during the study period; of those, 2670 (3.6%) were complicated by OASIS. The incidence of OASIS decreased during the study period from 4.3% (n = 636) in 2011 to 2.6% (n = 399) in 2015. There was a significant decrease in the incidence of OASIS at both the departments with formal prevention programs and those without. After adjustment for other important risk factors of OASIS, we found no significant difference in the risk reduction between departments with and without formal prevention programs. CONCLUSIONS: We found that the general focus on prevention of OASIS in Denmark was associated with a significant decrease in the incidence of OASIS, but implementation of formal prevention programs did not lead to a further reduction. It is possible that more rigorous interventions at the hospitals with formal prevention programs could have resulted in a significant difference in incidence of OASIS.

Long-term anal incontinence after obstetric anal sphincter injury-does grade of tear matter?

BACKGROUND: Anal incontinence is a major concern following delivery with obstetric anal sphincter injury (OASIS), and has been related to the degree of sphincter tear. OBJECTIVE: The aims of this study were (1) to evaluate whether women with a fourth-degree OASIS in the first delivery have an increased risk of long-term anal and fecal incontinence after a second delivery, and (2) to assess the impact of mode of second delivery on anal incontinence and related symptoms in these patients. MATERIALS AND METHODS: We performed secondary analyses of a national questionnaire study in all Danish women with an OASIS in their first delivery and 1 subsequent delivery, both deliveries in 1997 to 2005. The questionnaires were sent a minimum of 5 years since the second delivery. In Denmark, women with anal incontinence after a delivery with OASIS are recommended elective cesarean deliveries in subsequent pregnancies. We performed uni- and multivariable logistic regression analyses to evaluate the outcomes. RESULTS: In total, 2008 patients had an OASIS, of whom 12.2% (n = 245) had a fourth-degree tear in the first delivery. The median follow-up time since the first delivery with OASIS was 11.6 years (IQR, 10.2-13.2 years) and since the second delivery 8.5 years (IQR, 7.1-10.1 years). Women with a fourth-degree sphincter injury in the first delivery were at higher risk for anal incontinence (58.8%, n = 144) as well as fecal incontinence (30.6%, n = 75) than patients with a third-degree injury in the first delivery (41.0%, n = 723, and 14.6%, n = 258, respectively). The differences between groups persisted after adjustment for important maternal, fetal, and obstetric characteristics (adjusted odds ratio [aOR], 2.14; 95% confidence interval [CI], 1.52-3.02; P < 0.001 for anal incontinence; and aOR, 2.49; 95% CI, 1.73-3.56; P < 0.001 for fecal incontinence). In subgroup analyses of patients with fourth-degree anal sphincter injury in the first delivery, the mode of second delivery was not associated with the risk of anal incontinence (aOR, 0.97; 95% CI, 0.41-1.84; P = 0.71) or fecal incontinence (aOR, 1.28; 95% CI, 0.65-2.52; P = 0.48). The effect of the mode of the second delivery did not differ between women with a fourth-degree OASIS and those with a third-degree injury with regard to both anal (P = 0.09) and fecal (P = 0.96) incontinence. CONCLUSION: After a second delivery, women with a fourth-degree OASIS in the first delivery have a higher risk of long-term anal and fecal incontinence than women with a third-degree sphincter injury. Adjusted odds of long-term anal and fecal incontinence did not differ significantly by mode of second delivery. Women with a fourth-degree OASIS should be informed about the increased risk of long-term anal incontinence and advised that subsequent elective cesarean delivery is not protective.

Recurrent obstetric anal sphincter injury and the risk of long-term anal incontinence.

BACKGROUND: Women with an obstetric anal sphincter injury are concerned about the risk of recurrent obstetric anal sphincter injury in their second pregnancy. Existing studies have failed to clarify whether the recurrence of obstetric anal sphincter injury affects the risk of anal and fecal incontinence at long-term follow-up. OBJECTIVE: The objective of the study was to evaluate whether recurrent obstetric anal sphincter injury influenced the risk of anal and fecal incontinence more than 5 years after the second vaginal delivery. STUDY DESIGN: We performed a secondary analysis of data from a postal questionnaire study in women with obstetric anal sphincter injury in the first delivery and 1 subsequent vaginal delivery. The questionnaire was sent to all Danish women who fulfilled inclusion criteria and had 2 vaginal deliveries 1997-2005. We performed uni- and multivariable analyses to assess how recurrent obstetric anal sphincter injury affects the risk of anal incontinence. RESULTS: In 1490 women with a second vaginal delivery after a first delivery with obstetric anal sphincter injury, 106 had a recurrent obstetric anal sphincter injury. Of these, 50.0% (n = 53) reported anal incontinence compared with 37.9% (n = 525) of women without recurrent obstetric anal sphincter injury. Fecal incontinence was present in 23.6% (n = 25) of women with recurrent obstetric anal sphincter injury and in 13.2% (n = 182) of women without recurrent obstetric anal sphincter injury. After adjustment for third- or fourth-degree obstetric anal sphincter injury in the first delivery, maternal age at answering the questionnaire, birthweight of the first and second child, years since first and second delivery, and whether anal incontinence was present before the second pregnancy, the risk of flatal and fecal incontinence was still increased in patients with recurrent obstetric anal sphincter injury (adjusted odds ratio, 1.68 [95% confidence interval, 1.05-2.70), P = .03, and adjusted odds ratio, 1.98 [95% confidence interval, 1.13-3.47], P = .02, respectively). More women with recurrent obstetric anal sphincter injury reported affected the quality of life because of anal incontinence (34.9%, n = 37) compared with women without recurrent obstetric anal sphincter injury (24.2%, n = 335), although this difference did not reach statistical significance after adjustment (adjusted odds ratio, 1.53 [95% confidence interval, 0.92-2.56] P = .10). CONCLUSION: Women opting for vaginal delivery after obstetric anal sphincter injury should be informed about the risk of recurrence, which is associated with an increased risk of long-term flatal and fecal incontinence.

Tissue-engineering with muscle fiber fragments improves the strength of a weak abdominal wall in rats.

INTRODUCTION AND HYPOTHESIS: Alternative approaches to reinforce the native tissue in patients with pelvic organ prolapse (POP) are needed to improve surgical outcome. Our aims were to develop a weakened abdominal wall in a rat model to mimic the weakened vaginal wall in women with POP and then evaluate the regenerative potential of a quickly biodegradable synthetic scaffold, methoxypolyethylene glycol polylactic-co-glycolic acid (MPEG-PLGA), seeded with autologous muscle fiber fragments (MFFs) using this model. METHODS: In an initial pilot study with 15 animals, significant weakening of the abdominal wall and a feasible technique was established by creating a partial defect with removal of one abdominal muscle layer. Subsequently, 18 rats were evenly divided into three groups: (1) unrepaired partial defect; (2) partial defect repaired with MPEG-PLGA; (3) partial defect repaired with MPEG-PLGA and MFFs labeled with PKH26-fluorescence dye. After 8 weeks, we performed histopathological and immunohistochemical testing, fluorescence analysis, and uniaxial biomechanical testing. RESULTS: Both macroscopically and microscopically, the MPEG-PLGA scaffold was fully degraded, with no signs of an inflammatory or foreign-body response. PKH26-positive cells were found in all animals from the group with added MFFs. Analysis of variance (ANOVA) showed a significant difference between groups with respect to load at failure (p = 0.028), and post hoc testing revealed that the group with MPEG-PLGA and MFFs showed a significantly higher strength than the group with MPEG-PLGA alone (p = 0.034). CONCLUSION: Tissue-engineering with MFFs seeded on a scaffold of biodegradable MPEG-PLGA might be an interesting adjunct to future POP repair.

Anal incontinence after two vaginal deliveries without obstetric anal sphincter rupture.

PURPOSE: To evaluate prevalence and risk factors for long-term anal incontinence in women with two prior vaginal deliveries without obstetric anal sphincter injury (OASIS) and to assess the impact of anal incontinence-related symptoms on quality of life. METHODS: This is a nation-wide cross-sectional survey study. One thousand women who had a first vaginal delivery and a subsequent delivery, both without OASIS, between 1997 and 2008 in Denmark were identified in the Danish Medical Birth Registry. Women with more than two deliveries in total till 2012 were excluded at this stage. Of the 1000 women randomly identified, 763 were eligible and received a questionnaire. Maternal and obstetric data were retrieved from the national registry. RESULTS: The response rate was 58.3%. In total, 394 women were included for analysis after reviewing responses according to previously defined exclusion criteria. Median follow-up time was 9.8 years after the first delivery and 6.4 years after the second. The prevalence of flatal incontinence, fecal incontinence and fecal urgency were 11.7, 4.1, and 12.3%, respectively. Overall, 20.1% had any degree of anal incontinence and/or fecal urgency. In 6.3% these symptoms affected their quality of life. No maternal or obstetric factors including episiotomy and vacuum extraction were consistently associated with altered risk of anal incontinence in the multivariable analyses. CONCLUSIONS: Anal incontinence and fecal urgency is reported by one fifth of women with two vaginal deliveries without OASIS at long-term follow-up. Episiotomy or vacuum extraction did not alter the risk of long-term anal incontinence.

Mode of delivery after obstetric anal sphincter injury and the risk of long-term anal incontinence.

BACKGROUND: Primiparous women have an increased risk of obstetric anal sphincter injury; because most of these patients deliver again, there are major concerns about mode of delivery: the risk of recurrent obstetric anal sphincter injury and the risk of long-term symptoms of anal incontinence. Although an elective cesarean delivery protects against recurrent obstetric anal sphincter injury, it is uncertain how the second delivery affects the risk of long-term anal incontinence. OBJECTIVE: The purpose of this study was to evaluate whether the mode of delivery for a second pregnancy, after a documented obstetric anal sphincter injury at the time of first delivery, had a significant impact on the prevalence of anal and fecal incontinence in the long term. STUDY DESIGN: We performed a population-based questionnaire cohort study that evaluated anal and fecal incontinence, fecal urgency, and affected quality of life caused by anal incontinence in 1978 patients who had obstetric anal sphincter injury in the first delivery and a second vaginal (n = 1472 women; 71.9%) or elective cesarean delivery (n = 506 women; 24.7%) delivery. We performed uni- and multivariable logistic regression analyses to compare groups. RESULTS: Long-term anal incontinence was reported in 38.9% of patients (n = 573) with second vaginal compared with 53.2% (n = 269) with elective cesarean delivery. The corresponding numbers that reported anal incontinence before the second pregnancy was 29.4% for those with vaginal delivery compared with 56.2% of those with elective cesarean delivery (ie, there was a significantly larger change in the risk of anal incontinence in the group with a second vaginal delivery compared with the change in the group with elective cesarean in second delivery). However, adjusted for important maternal and obstetric characteristics, the risk of long-term anal incontinence was nonsignificantly lower in patients with elective cesarean delivery (adjusted odds ratio, 0.77; 95% confidence interval, 0.57-1.05; P = .09). Furthermore, the risk of fecal incontinence was not affected by mode of delivery in the multivariable analysis (adjusted odds ratio, 1.04; 95% confidence interval, 0.76-1.43; P = .79). Patients with persistent anal incontinence before the second pregnancy (n = 496) had an increased risk of long-term anal incontinence (adjusted odds ratio, 64.70; 95% confidence interval, 42.85-97.68; P < .001) and long-term fecal incontinence (adjusted odds ratio, 13.76, 95% confidence interval, 10.03-18.88, P<0.001) compared with patients without anal incontinence before the second pregnancy. CONCLUSION: Mode of second delivery did not significantly affect the risk of long-term anal or fecal incontinence in multivariable analyses of patients with previous obstetric anal sphincter injury in this population in which patients with anal incontinence before the second pregnancy were recommended to have an elective cesarean delivery in the subsequent delivery. Nonetheless, we found that patients with vaginal delivery had a higher risk of deterioration of anal incontinence symptoms compared with those with an elective cesarean delivery.

Muscle fragments on a scaffold in rats: a potential regenerative strategy in urogynecology.

INTRODUCTION AND HYPOTHESIS: The use of permanent synthetic meshes to improve the outcome of pelvic organ prolapse (POP) repair causes frequent and serious complications. The use of the synthetic, biodegradable scaffold methoxypolyethyleneglycol-polylactic-co-glycolic acid (MPEG-PLGA) seeded with autologous muscle fiber fragments (MFF), as an adjunct to native tissue POP repair, is a potential new alternative. METHODS: A rat abdominal wall model of native repair was used with six animals in each of three groups: native repair, native repair + MPEG-PLGA, and native repair + MPEG-PLGA + MFF. MFF were labeled with PKH26-fluorescence dye. After 8 weeks labeled cells were identified in tissue samples and histopathological and immunohistochemical analyses of connective tissue organization and desmin reactivity of muscle cells were performed. Fresh tissue samples were subjected to uniaxial biomechanical testing. Statistical analyses were performed using one-way analysis of variance (ANOVA). RESULTS: MPEG-PLGA was fully degraded after 8 weeks. Desmin-immunopositive (6/6) and PKH26-positive cells (6/6) were found only after native repair + MPEG-PLGA + MFF, indicating survival, proliferation, and integration of cells originating from the MFF. This group also showed significantly increased stiffness in the high stiffness zone compared with native repair + MPEG-PLGA (p = 0.032) and borderline significantly higher stiffness compared to native repair (p = 0.054). CONCLUSIONS: In this pilot study, MPEG-PLGA scaffolds seeded with autologous MFF affected some histological and biomechanical properties of native tissue repair in an abdominal wall defect model in rats. The method thus appears to be a simple tissue engineering concept with potential relevance for native tissue repair of POP.

Modifiable risk factors of obstetric anal sphincter injury in primiparous women: a population-based cohort study.

OBJECTIVE: To determine modifiable risk factors and incidence of obstetric anal sphincter injury (OASIS) in primiparous women. STUDY DESIGN: We performed a population-based retrospective cohort study, using data from the Danish Medical Birth Registry. The population consisted of primiparous women with a vaginal delivery in the time period 2000-2010. Univariable and multivariable logistic regressions were used to determine risk factors of OASIS. Main outcome measures were incidence of OASIS in first vaginal delivery, odds ratios for possible risk factors: age, body mass index, birthweight, head circumference, gestational age, presentation, induction of labor, oxytocin augmentation, epidural, mediolateral episiotomy, vacuum extraction, forceps, shoulder dystocia, and year of delivery. RESULTS: Of 214,256 primiparous women with a vaginal delivery, 13,907 (6.5%; 95% confidence interval [CI] 6.4-6.6%) experienced an OASIS. The incidence of OASIS increased in the time period (adjusted odds ratio [aOR], 1.02; 95% CI, 1.02-1.03; P < .0001, per year). We found a protective effect of epidural analgesia (aOR, 0.84; 95% CI, 0.81-0.88; P = .0001). Vacuum extraction without episiotomy was a significant risk factor of OASIS (aOR, 2.99; 95% CI, 2.86-3.12; P < .0001), and episiotomy was protective in vacuum-assisted deliveries compared with vacuum-assisted deliveries without episiotomy (aOR, 0.60; 95% CI, 0.56-0.65; P < .0001). Birthweight was found to be an important nonmodifiable risk factor (aOR, 2.76; 95% CI, 2.62-2.90; P < .0001). CONCLUSION: Epidural analgesia in itself was protective against OASIS. Vacuum extraction increased the risk of OASIS, although mediolateral episiotomy was protective when applied in deliveries assisted by vacuum extraction.

The REPAIR study: oral antibiotics to prevent infection and wound dehiscence after obstetric perineal tear-a double-blinded placebo controlled randomized trial.

BACKGROUND: Approximately 85% of women experience an obstetric tear at delivery and up to 25% subsequently experience wound dehiscence and/or infection. Previous publications suggest that intravenous antibiotics administrated during delivery reduces this risk. We do not know if oral antibiotics given after delivery can reduce the risk of wound dehiscence or infection. Our aim is to investigate whether three doses of oral antibiotics (amoxicillin 500 mg/clavulanic acid 125 mg) given after delivery can reduce the risk of wound dehiscence and infection in patients with a second-degree obstetric tear or episiotomy. METHODS: We will perform a randomized, controlled, double-blinded study including 221women in each arm with allocation 1:1 in relation to the randomization. The study is carried out at Department of Obstetrics & Gynecology, Herlev University Hospital, Copenhagen, Denmark. The women will be included after delivery if they have had a second-degree tear or episiotomy. After inclusion, the women will have a clinical follow-up visit after 1 week. The tear and healing will be evaluated regarding signs of infection and/or dehiscence. The women will again be invited for a 1-year clinical examination including ultrasound. Questionnaires exploring symptoms related to the obstetric tear and possible complications will be answered at both visits. Our primary outcome is wound dehiscence and/or wound infection, which will be calculated using χ2 tests to compare groups. Secondary outcomes are variables that relate to wound healing, as pain, use of painkillers and antibiotics, need for further follow-up, as well as outcomes that may be related to the birth or healing process, urinary or anal incontinence, symptoms of prolapse, female body image, and sexual problems. DISCUSSION: Reducing the risk of wound dehiscence and/or infection would decrease the number of control visits, prevent the need for longer antibiotic treatment, and possibly also decrease both short-term and long-term symptoms. This would be of great importance so the mother, her partner, and the baby could establish and optimize their initial family relation. TRIAL REGISTRATION: The conduction of this study is approved the 2/2-2023 with the EU-CT number: 2022-501930-49-00. CLINICALTRIALS: gov Identifier: NCT05830162.

Tissue - engineering as an adjunct to pelvic reconstructive surgery.

This PhD-thesis is based on animal studies and comprises three original papers and unpublished data. The studies were con-ducted during my employment as a research fellow at the Department of Obstetrics and Gynecology, Herlev University Hospital, Denmark. New strategies for surgical reconstruction of pelvic organ pro-lapse (POP) are warranted. Traditional native tissue repair may be associated with poor long-term outcome and augmentation with permanent polypropylene meshes is associated with frequent and severe adverse effects. Tissue-engineering is a regenerative strategy that aims at creating functional tissue using stem cells, scaffolds and trophic factors. The aim of this thesis was to investigate the potential adjunctive use of a tissue-engineering technique for pelvic reconstructive surgery using two synthetic biodegradable materials; methoxypolyethyleneglycol-poly(lacticco-glycolic acid) (MPEG-PLGA) and electrospun polycaprolactone (PCL) - with or without seeded muscle stem cells in the form of autologous fresh muscle fiber fragments (MFFs). To simulate different POP repair scenarios different animal models were used. In Study 1 and 2, MPEG-PLGA was evaluated in a native tissue re-pair model and a partial defect model of the rat abdominal wall. We found that the scaffold was fully degraded after eight weeks. Cells from added MFFs could be traced and had resulted in the formation of new striated muscle fibers. Also, biomechanical changes were found in the groups with added MFFs. In Study 3, the long-term degradable electrospun PCL scaffold was evaluated in three rat abdominal wall models representing different loads on the scaffold. Surprisingly, cells from the MFFs did not survive. After eight weeks, a marked inflammatory foreign-body response was observed with numerous giant cells located between and around the PCL fibers which appeared not to be degraded. This response caused a considerable increase in the thickness of the mesh, resulting in a neotissue PCL construct with strength comparable to that of normal rat abdominal wall. The foreign-body inflammatory response did not differ between the groups in terms of cellularity, cell types or thickness, and no differences were found between groups when comparing biomechanical properties. In study 4, we modified a new transabdominal rabbit vaginal model to avoid the erosions known to occur following vaginal mesh implantation. A partial defect was created on the anterior vaginal wall in the vesico-vaginal space and on the anterior vaginal wall close to the cervix. This was a feasibility study aimed at obtaining results comparable to those seen in the rat model. The model was easy to perform and no vaginal erosions were observed. IN CONCLUSION: In two rat abdominal wall models, cells from autologous MFFs, seeded on the quickly degradable MPEG-PLGA scaf-fold, survived implantation and contributed to the regenerative process by forming extra striated muscle fibers and influencing the biomechanical properties of the regenerated tissue. Consequently, MFFs seeded on an MPEG-PLGA scaffold is a potentially advantageous cell-delivering strategy to regenerate tissue at pelvic reconstructive surgery. In three rat abdominal wall models, a long-term degradable PCL scaffold caused a marked foreign-body response and formed a neo-tissue PCL construct that provided biomechanical tissue reinforcement to the abdominal wall, even at maximal load. Consequently, the PCL scaffold might be beneficial in pelvic reconstructive surgery, providing initial biomechanical rein-forcement, although long-term studies showing the tissue response at full degradation are required. Cells from the MFFs did not survive in or around the neo-tissue PCL construct, possibly because of the massive inflammatory response. Consequently, as a scaffold material, with the purpose of delivering cells to a specific anatomical site, the PCL scaffold seems poor. A transabdominal rabbit vaginal model was feasible and might be advantageous in the evaluation of meshes used for pelvic reconstructive surgery, especially when long-term studies are needed.

Examinations of a new long-term degradable electrospun polycaprolactone scaffold in three rat abdominal wall models.

Alternative approaches to reinforce native tissue in reconstructive surgery for pelvic organ prolapse are warranted. Tissue engineering combines the use of a scaffold with the regenerative potential of stem cells and is a promising new concept in urogynecology. Our objective was to evaluate whether a newly developed long-term degradable polycaprolactone scaffold could provide biomechanical reinforcement and function as a scaffold for autologous muscle fiber fragments. We performed a study with three different rat abdominal wall models where the scaffold with or without muscle fiber fragments was placed (1) subcutaneously (minimal load), (2) in a partial defect (partial load), and (3) in a full-thickness defect (heavy load). After 8 weeks, no animals had developed hernia, and the scaffold provided biomechanical reinforcement, even in the models where it was subjected to heavy load. The scaffold was not yet degraded but showed increased thickness in all groups. Histologically, we found a massive foreign body response with numerous large giant cells intermingled with the fibers of the scaffold. Cells from added muscle fiber fragments could not be traced by PKH26 fluorescence or desmin staining. Taken together, the long-term degradable polycaprolactone scaffold provided biomechanical reinforcement by inducing a marked foreign-body response and attracting numerous inflammatory cells to form a strong neo-tissue construct. However, cells from the muscle fiber fragments did not survive in this milieu. Properties of the new neo-tissue construct must be evaluated at the time of full degradation of the scaffold before its possible clinical value in pelvic organ prolapse surgery can be evaluated.

Episiotomy in vacuum-assisted delivery affects the risk of obstetric anal sphincter injury: a systematic review and meta-analysis.

The risk of obstetric anal sphincter injury (OASIS) is increased in vacuum-assisted delivery. However, it remains unclear whether episiotomy may protect against OASIS in this type of delivery. The objective of this study was to assess whether mediolateral or lateral episiotomy affects the risk of OASIS in vacuum-assisted delivery among primiparous women. Data were found searching The PubMed, Cochrane library and Embase databases electronically. Studies investigating the risk of OASIS in vacuum-assisted delivery with and without the use of mediolateral or lateral episiotomy were considered for inclusion. Of the 452 studies found, 15 observational studies were included in this meta-analysis. All authors assessed risk of bias of the included studies using the Scottish Intercollegiate Guideline Network (SIGN) quality score. According to this meta-analysis, mediolateral or lateral episiotomy significantly reduced the risk of OASIS in vacuum-assisted deliveries in primiparous women (OR 0.53 (95% CI 0.37-0.77)). Numbers needed to treat (NNT) was 18.3 (95% CI 17.7-18.9). The protective effect of episiotomy seemed most pronounced when performed in more than 75% of vacuum-assisted deliveries (OR 0.37 (95% CI 0.15-0.92)). In conclusion, this meta-analysis showed that mediolateral or lateral episiotomy was protective against OASIS and may be considered in vacuum-assisted delivery in primiparous women. Randomized controlled trials to further investigate this finding are warranted.