Quality of Life Following Pelvic Organ Prolapse Treatments in Women: A Systematic Review and Meta-Analysis

Introduction: Quality of life (QoL) improvement is one of the main outcomes in the management of pelvic organ prolapse as a chronic illness in women. This systematic review aimed to investigate the impact of surgical or pessary treatment for pelvic organ prolapse (POP) on quality of life. Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was applied. Electronic databases, including PubMed, Scopus, and Web of Science, were searched for original articles that evaluated the QoL before and after surgical interventions or pessary in pelvic organ prolapse from 1 January 2012 until 30 June 2022 with a combination of proper keywords. Included studies were categorized based on interventions, and they were tabulated to summarize the results. Results: Overall, 587 citations were retrieved. Of these, 76 articles were found eligible for final review. Overall, three categories of intervention were identified: vaginal surgeries (47 studies), abdominal surgeries (18 studies), and pessary intervention (11 studies). Almost all interventions were associated with improved quality of life. The results of the meta-analysis showed a significant association between the employment of surgical approach techniques (including vaginal and abdominal surgeries) and the quality of life (Pelvic Floor Distress Inventory (PFDI) (MD: −48.08, 95% CI: −62.34 to −33.77, p-value < 0.01), Pelvic Floor Impact Questionnaire (PFIQ) (MD: −33.41, 95% CI: −43.48 to −23.34, p < 0.01)) and sexual activity of patients with pelvic organ prolapse (Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ) (MD: 4.84, 95% CI: 1.75 to 7.92, p < 0.01)). Furthermore, narrative synthesis for studies investigating the effect of the pessary approach showed a positive association between the use of this instrument and improvement in the quality of life and sexual activity. Conclusions: The results of our study revealed a significant improvement in the women’s quality of life following abdominal and vaginal reconstructive surgery. The use of pessary was also associated with increased patient quality of life.


Introduction
Pelvic organ prolapse (POP) occurs due to weakness of the supportive tissues of the pelvic organs, which may lead to prolapse of the anterior and/or posterior vaginal wall, the uterus (cervix), or the apex of the vagina (vaginal vault or cuff scar after hysterectomy) [1]. The prevalence of POP is currently increasing due to extended life expectancies and childbearing in low-resource areas [2]. Pelvic prolapses are not always symptomatic and can lead to discomfort in the vagina and changes in bladder and bowel function that can greatly affect women's quality of life [3], with general, social, psychological, and sexual impacts [4]. 2 of 31 Therefore, improving the quality of life is one of the main outcomes in the management of pelvic organ prolapse in women [5].
Surgical interventions for POP include repairing with native tissue or mesh and minimally invasive surgeries such as laparoscopic or robotic techniques, which are increasing in popularity [6]. The selection of the intervention depends on several factors, such as the site and severity of the POP; additional symptoms that affect urinary, bowel, or sexual function; the wish to preserve the uterus; and the surgeon's choice and ability. Surgical treatment options include vaginal or abdominal (laparotomy, laparoscopy, and, more recently, robotic approach) [7]. There are also conservative interventions, which are defined as non-surgical methods such as optimizing lifestyle (weight loss and avoiding heavy lifting or coughing) and physical therapies [8]. In the last decades, pessaries, which have existed since the beginning of recorded history, have also been used in women with POP [9]. These are removable devices that provide support after prolapse [9]. Various instruments have been designed to assess the quality of life (QoL). Some of them evaluate the general aspect, whereas others, such as the Pelvic Organ Prolapse Distress Inventory (POPDI-6) and Pelvic Organ Prolapse Impact Questionnaire (POPIQ-7), are specific for POP [10,11]. Some questionnaires are dedicated to the quality of sex life [12].
QoL studies for POP are very diverse, with different methods, instruments, and followups. Therefore, studies that summarize the results and provide final recommendations are scarce. Performing a systematic review is the best way to summarize the effects of POP treatment on QoL. A similar study was performed in 2012 by Doaee et al. that examined articles over the past ten years [13]. Due to the advances in urogynecological surgery and other interventional methods such as pessaries, updating this data seems necessary. The current study aims to review those studies that have focused on changing the QoL by means of surgery or pessary for POP management.

Methods
The current systematic review was designed to review QoL in women before and after surgery or pessary intervention for POP management in English biomedical journals. The study is reported based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement [14].

Eligibility Criteria
The inclusion criteria were as follows: (1) study design: all original articles including randomized clinical trials, observational studies (cross-sectional, case-control, or cohort), and editorials/letters; (2) patient population and intervention: adult women with POP who received surgical treatments or pessary intervention for POP management; and (3) outcome: evaluated quality of life using available questionnaires. Review articles, opinions or guidelines, conference abstracts, non-peer-reviewed papers, case reports, unpublished reports, and articles in which the date and location of the study were not specified were excluded.

Information Sources
The initial search was undertaken in three main databases including articles published in MEDLINE (through PubMed), Scopus, and Web of Science from 1 January 2012 until 31 June 2022. Additionally, a manual search in the reference section of the relevant studies was done to obtain possible publications that were missed in our electronic search.

Search Strategy
To retrieve citations on the topic based on the medical subject heading (Mesh), a combination of the following keywords was used: 'pelvic organ prolapses', 'quality of life', and 'treatment'. The study time frame was also applied to all databases. A full search strategy for each database is available in the Supplementary Materials.

Study Selection
Titles and abstracts were independently reviewed for eligibility by three authors (PJ, RH, and SP), and non-relevant or duplicate studies that did not meet the inclusion criteria were excluded. In cases of disagreement, the problem was resolved by discussion and the main author (ZG.). After initial screening, the full texts of the articles were reviewed, and the unrelated articles were removed.

Quality Assessment
NS and AS independently assessed the quality of the included studies using the National Heart, Lung, and Blood Institute (NHLBI) tools [15]. Based on the design of a study (whether a randomized controlled trial or a cohort), an individual checklist that contains 14 signaling questions for assessing the quality of each study was used. Briefly, studies scoring nine or more "Yes" answers were marked as "Good", studies scoring between seven or eight were marked as "Fair", and studies rating less than seven were marked as "Poor" quality.

Data Extraction
The data-including the first author, publication date and study design, intervention mode, using mesh or native tissue, sample size, stage of prolapse and prolapse type, main findings, and the instrument used to measure the QoL, as well as the follow-up duration and quality of papers-were extracted and tabulated.

Statistical Analysis
We used the mean difference (MD) of the total quality of life questionnaire values before and after the intervention. Using a random effect model, the quantitative values of each study were pooled separately. If the MD was not given in the specific study, an estimate was made using Excel calculators [16]. The Pelvic Floor Distress Inventory Questionnaire (PFDI) and Pelvic Floor Impact Questionnaire (PFIQ-7) were used as the main measures for pooling the results of the studies regarding the QoL of patients. Furthermore, the PISQ and FSFI questionnaires were used to pool the data regarding the sexual activity of patients after the intervention. We used Cochran's Q statistic (Q-test) and the I2 to assess heterogeneity. I2 value >75% indicated a high amount of heterogeneity. Publication bias was assessed by visual inspection of the funnel plot, and Egger's test with a significance level of 0.05 was used to evaluate the publication bias. All analyses were statistically significant with a p-value < 0.05. The analyses were performed using R-4.1.3 software and the Meta package (R Core Team, Vienna, Austria; available at https://www.R-project.org/, accessed on 6 January 2022).

Registration Statement
We have written the protocol of this study, but due to the high diversity of studies and quality of life assessment methods, we did not register it due to the high possibility of changes in the protocol

Statistics
Overall, 587 citations were found to be eligible. After excluding 435 duplicates, 122 studies were screened by the title and abstract. By excluding 21 citations, 100 full text articles were reviewed, and 76 articles were finally eligible for final evaluations. The flowchart of the study is depicted in Figure 1. articles were reviewed, and 76 articles were finally eligible for final evaluations. The flowchart of the study is depicted in Figure 1.

Instrument Used
A wide variety of questionnaires were used to measure patient-reported outcomes, including QoL measures. Of these, some were the general measures, and several instruments were pelvic-specific QoL questionnaires. Some instruments are used for measuring sexual QoL in sexually active women. The most common general instruments were the 36-Item Short Form Survey (SF-36) and Patient Global Impression of Improvement (PGI-I), while the pelvic-specific measures were the Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12), Prolapse Quality of Life (P-QOL), and Pelvic Floor Impact Questionnaire-7 (PFIQ-7). The Sexual QoL was measured by the Female Sexual Function Index (FSFI). The questionnaires are listed in Table 1. Table 1. Questionnaires used in the recruited studies.

Instrument Used
A wide variety of questionnaires were used to measure patient-reported outcomes, including QoL measures. Of these, some were the general measures, and several instruments were pelvic-specific QoL questionnaires. Some instruments are used for measuring sexual QoL in sexually active women. The most common general instruments were the 36-Item Short Form Survey (SF-36) and Patient Global Impression of Improvement (PGI-I), while the pelvic-specific measures were the Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12), Prolapse Quality of Life (P-QOL), and Pelvic Floor Impact Questionnaire-7 (PFIQ-7). The Sexual QoL was measured by the Female Sexual Function Index (FSFI). The questionnaires are listed in Table 1.

General Findings
To facilitate reporting the results, papers were classified into three categories: vaginal surgeries (47 articles), abdominal surgeries (18 articles), and pessary interventions (11 articles). These are categorized in Figure 2

General Findings
To facilitate reporting the results, papers were classified into three categories: vaginal surgeries (47 articles), abdominal surgeries (18 articles), and pessary interventions (11 articles). These are categorized in Figure 2.
Overall, 60.5% (23/38) of the reconstructive studies used mesh for repairing. In a recent study, transvaginal mesh surgery and laparoscopic mesh sacropexy had similar results [9]. In addition, in one cohort study, QoL was measured after POP surgery with or without mesh and did not differentiate between individuals with and without mesh [31]. All studies investigated the QoL in the first surgery, except one, which evaluated the transvaginal bilateral sacrospinous fixation after the second recurrence of vaginal vault prolapse, which improved the QoL and sexual function [61].
Overall, 60.5% (23/38) of the reconstructive studies used mesh for repairing. In a recent study, transvaginal mesh surgery and laparoscopic mesh sacropexy had similar results [9]. In addition, in one cohort study, QoL was measured after POP surgery with or without mesh and did not differentiate between individuals with and without mesh [31]. All studies investigated the QoL in the first surgery, except one, which evaluated the transvaginal bilateral sacrospinous fixation after the second recurrence of vaginal vault prolapse, which improved the QoL and sexual function [61].

Abdominal Surgeries
Overall, eight [33,47,48,56,[74][75][76]87] and two studies [53,54] were dedicated to just laparoscopic or robotic approaches, respectively (Table 5). Four citations compared vaginalassisted laparoscopic sacrohysteropexy and vaginal hysterectomy with vaginal vault suspension for advanced uterine prolapse, which has similar results [45,49,50,55]. Another study compared two methods of laparoscopic and robotic ventral mesh rectopexy, and the results had no difference [51]. One study compared robotic and vaginal sacropexy with comparable results, and in one study, three methods were compared [46]. Preoperative scores of all domains on the ICIQ-VS and P-QoL were significantly higher than those at three and six months after surgery (p < 0.0001).

months
The P-QOL scores were either low (<40) or very low (<20) after the intervention, indicating a high QOL among patients.  Single anterior vaginal mesh acted better than anterior/posterior mesh.

Good
Only one study was on laparotomy [77], and another citation evaluated the difference between vaginal (using native tissue or with a mesh prolapse) and abdominal (open or robotic abdominal sacrocolpopexy), with results in favor of the abdominal group [78].

Overall Findings and Meta-Analysis
Almost all interventions, including surgery and pessary interventions, were associated with improved quality of life. In cases where two different surgical or surgical and pessary methods were compared, the results were inconsistent.

Discussion
In this systematic review, we found that the QoL was significantly improved in women after surgical or pessary interventions for the management of POP. We performed a metaanalysis of QoL and sexual activity questionnaires. The results of the meta-analysis showed a significant association between surgical approach techniques (including vaginal and abdominal surgeries) and improved QoL and sexual activity of patients with POP. Due to vast heterogeneity in the pessary approach and QoL questionnaires used, we were not able to pool the results of studies regarding pessary. However, descriptive analysis showed an improved quality of life in these patients.
Interventional and observational studies dedicated to POP surgeries or using pessaries have grown significantly in the last decade [90,91]. On the other hand, with the emergence of specialized QoL questionnaires for pelvic organ prolapse and its symptoms, we encounter a significant amount of data concerning QoL in different methods [92].
As mentioned before, we divided the studies into three parts based on the intervention approach. In vaginal studies, we also dealt with reconstructive and obliterative methods. Increasing numbers of elderly women and their co-morbidities have increased the preference for obliterative vaginal surgery, due to high levels of durability with lower rates of morbidity. Obliterative methods seem to be a good method for older women who are not sexually active and could not tolerate major surgeries with good durability and relative ease of surgery [90,93]. Few studies evaluated the QoL of patients following obliterative methods. The results of these surgeries were satisfactory, and in two studies that were compared with other methods, the results were contradictory [18,72].
Reconstructive methods using synthetic meshes for pelvic organ prolapse and/or stress urinary incontinence have been popular since the mid-1990s [50]. Mesh repairs were effective as traditional repairs [81] and improve QoL [26]. Patients may benefit from anatomical stability when the risks are justifiable [7], with a low rate of recurrence and few complications [7]. However, reports of mesh-related complications are increasing [7,90], and the Food and Drug Administration (FDA) recently warned about using transvaginal mesh due to adverse events including vaginal erosion, dyspareunia, pain, and infection [57,92].
However, there is no consensus in this regard, and the use of mesh is recommended by some experts.
With regard to abdominal approaches, three different approaches were evaluated in the studies. Laparoscopic sacrocolpopexy and sacrohysteropexy have been demonstrated to be effective and safe with faster recovery time, shorter operating time, lower blood loss, lower scar tissue, lower pain, and minimally invasive nature compared to the abdominal approaches [94]. However, these procedures have been associated with some complications, such as stress urinary incontinence [95], defecation problems [96], and injuries of the presacral venous plexus [97]. On the other hand, robotic surgeries have recently been introduced with good results and improvement in QoL. A systematic review and meta-analysis showed less intraoperative bleeding, lower incidence of postoperative complications, and shorter hospital stay for RVMR compared with LVMR, but found no differences in rates of recurrence, conversion, or reoperation [98].
Finally, the vaginal pessary is a conservative treatment for pelvic organ prolapse and can be offered as the first-line treatment in most patients [99]. Non-surgical modalities such as pessary are the best choice for older women because most of them have some type of cardiovascular disease [100] or diabetes mellitus [101]. Among various vaginal pessaries, the ring pessary is the most common type because it is convenient to insert and remove and has acceptable continuation rate and manageable adverse events. In addition, a ring with support pessary is a safe and effective conservative treatment for POP; it not only relieves bothersome prolapse and urinary symptoms but also significantly decreases their impacts on health-related QoL. One-quarter of the patients discontinued using pessary mainly due to dissatisfaction with pessary effectiveness or adverse events such as vaginal discharge or vaginal erosion [102]. Some women also prefer surgery after a while. Pessary treatment is continued beyond 12 months after initial placement by 63% of patients [34]. Comparative studies between pessary and surgery are not numerous, and their results are contradictory. In one study, women had the same quality of life [80], while in another study, women who underwent surgery reported a better QoL than pessary users [34].
In this study, we also had some limitations. First, due to the differences in the questionnaires used, variation in follow-up duration, and different methods of surgery, there was a significant amount of heterogeneity in the results of our meta-analysis. Furthermore, we only investigate a limited number of questionnaires available for assessing QoL patients with POP in our quantitative synthesis. However, it is worth noting that the results of other questionnaires were in line with our meta-analysis, which showed improved QoL of these patients after the aforementioned approaches were used. The conclusions of the metaanalysis were made mostly from the results of a limited number of observational studies, which lowers the certainty of evidence because of their observational nature. However, the results of almost all studies included in this systematic review were in line with our findings. Pelvic floor surgeries are relatively new and have made great strides in the last decade. It is suggested that, in future studies, the methods used with mesh be analyzed in a more specialized way.

Conclusions
QoL is significantly improved in women after surgical or pessary interventions for management of POP. Due to the daily progress of urogynecological and modern technologies in surgery and less invasive treatments, long-term cohort studies are recommended to evaluate the QoL in these people.