The effectiveness and safety of laparoscopic uterosacral ligament suspension: A systematic review and meta‐analysis

Laparoscopic uterosacral ligament suspension (LUSLS) is a technique to correct apical pelvic organ prolapse (POP) by shortening the uterosacral ligaments with sutures.

This leads to a more posterior and unilateral fixation of the vaginal axis.SSF has proven to be effective for apical prolapse but has higher recurrence rates than SC, 3 especially in the apical compartment.A recent meta-analysis 3 has shown that dyspareunia after SSF is more common than after SC (13% versus 9%, P = 0.03).Moreover, this procedure is not always technically possible, for example in women with a short vaginal length after prior POP surgery or hysterectomy.
Laparoscopic sacral colpopexy (LSC), on the other hand, uses abdominal mesh.Mesh is effective in the treatment of pelvic organ prolapse; however, vaginal mesh has led to serious complications in some patients.This resulted in a thorough safety review by the IMMDS (United Kingdom Independent Medicines and Medical Devices Safety Review), credentialling a smaller number of centres and surgeons for complex pelvic mesh surgeries with strict monitoring, and withdrawal of several mesh products from the market (ICS statement and IMMDS safety report 4,5 ).Even though the use of abdominal mesh has a lower risk of complications compared with vaginal mesh, 6,7 a growing number of women and physicians have reservations regarding the use of mesh and prefer native tissue repair. 7ne of the POP treatment options for apical pelvic organ prolapse is uterosacral ligament suspension (USLS).In this technique, uterosacral ligaments are grasped as proximally as possible and sutured to the apex of the vagina or cervix.][10] The vaginal axis and vaginal length are both maintained. 11ther vaginal procedures for apical POP using the uterosacral ligaments are the McCall procedure after vaginal hysterectomy and the modified Manchester Fothergill (MF) procedure.Due to a different surgical technique, the uterosacral ligaments are not plicated as high as with the HUSLS.Two studies comparing these techniques showed that the HUSLS resulted in better apical suspension. 12,13A review in 2010 of the effectivity of the HUSLS and McCall showed very high effectivity of the HUSLS as well: anatomic success of the apical compartment was achieved in 98% of women. 14A downside of the HUSLS is the limited view on the ureter, which lies close to the target area of the USLS.Ureteral injury and/or obstruction by kinking is a potential complication of this procedure; a peri-operative cystoscopy is therefore standardly performed. 10he advantage of the LUSLS over the HUSLS is the superior visualisation of the anatomy and localisation of the ureters.This minimalises the risk of ureteral injury and obstruction compared with HUSLS, allowing safe high suture placement and good apical support. 8,9lthough the theoretical advantages of the LUSLS are clear, this technique is not widely applied.The aim of this systematic review is to describe the effectiveness and safety of LUSLS as a treatment option for apical prolapse in patients with and without a uterus.

| Search strategy
The search was performed using the PubMed and Cochrane database with the help of an independent librarian.Search terms were 'pelvic organ prolapse', 'laparoscopy' and 'uterosacral'.The synonyms of these keywords were included as well (Supporting Information).The final search was conducted on 2 May 2022.References from relevant studies were checked for eligibility.

| Study selection
Two independent reviewers selected articles for further analysis by screening titles and abstracts (ALC, CV).In the case of disagreement between the two reviewers, a third reviewer made the final decision (PM/BS).All remaining articles were read fully by two reviewers (BS/CV).
Articles were eligible for inclusion if they met the following criteria: (a) laparoscopic surgical technique, (b) plication or reattachment of the uterosacral ligaments to the cervix or vaginal vault with sutures, (c) treatment for uterovaginal or vaginal vault prolapse, (d) presenting original objective and/ or subjective outcome measures.Articles in English were included.
Exclusion criteria were case reports, meta-analyses, robotic surgery, mesh surgery and studies that used LUSLS as standard procedure in non-prolapse surgery (prophylaxis).As it is the first review on this subject, we did not impose any other limits on study design, population or follow-up.An overview of the selection procedure is shown in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 15 flowchart (Figure 1).

| Data extraction
Data extraction was performed by two independent reviewers (PM/BS, CV).Collected data contained information on study design, baseline characteristics of participants, inclusion and exclusion criteria, description of the technique used, peri-operative data, complications, length of follow-up, results of objective and subjective outcome measures (such as Pelvic Organ Prolapse Quantification [POP-Q] or Baden Walker grade, 16 POP symptoms, satisfaction rates) and reoperation rate.All available data were extracted.

| Outcome measures
Our primary outcome measure was effectiveness of the procedure, both objective (anatomic results) and subjective (patient-reported outcome).Data on pre-and postoperative POP-Q stage of the apical compartment were used to pool data.The anatomic success rate was defined as the percentage of women with successful surgery (apical POP-Q stage 0-1 16 at the end of follow-up) out of women with a preoperative stage ≥2 apical POP.
The subjective cure rate was calculated in all studies reporting subjective outcome.If the PGI-I scale was used, we determined success as 'much improved' or 'very much improved'.If this was not available, success was defined as the absence of POP symptoms.
Our secondary outcomes were safety, recurrence and reoperation for apical prolapse.
Safety was measured by complication rate according to the Clavien-Dindo Classification. 17This is a validated grading system based on severity.Grade I-II complications resolve on their own or can be treated with medication.Grade III complications require re-operation or an extra surgical intervention perioperatively.Grade IV complications are life-threatening and Grade V complications lead to death.We calculated the complication rate as percentage per procedures.
For the analysis of recurrence and re-operations for apical prolapse, only studies with a follow-up period of ≥12 months were included.
Outcomes of LUSLS with preservation of the uterus versus LUSLS with concomitant hysterectomy were compared.To enable a fair comparison, the authors of all studies with outcome of a mixed patient population (a mix of patients with uterus preservation/concomitant hysterectomy/LUSLS on vaginal vault) were contacted to obtain separate data.If the authors were not reached after several attempts, these articles were excluded from this sub-analysis.
Estimated mean individual follow-up was calculated as the sum of participants per study × follow-up in months per study/total participants.

| Analysis
A systematic review of the literature on LUSLS was performed according to the PRISMA checklist. 15Effect measures were collected.Continuous variables were expressed as median or mean with standard deviation or range if available, and nominal variables using number and percentage.Primary and secondary outcomes were pooled for metaanalysis.A proportions calculation was performed using the statistical software MEDCALC to calculate a weighted average with 95% confidence intervals (95% CI).If heterogeneity (I 2 ) was present, the random effects model was used; if not, the fixed effects model was used.Outcomes not suitable for pooling are displayed in an overview table, showing the number of patients and number of studies reporting the outcome variable.

| Assessment of risk of bias
The Newcastle-Ottawa scale (NOS) was used: a risk of bias assessment tool for observational studies. 18With this tool, a total of nine stars can be obtained in the categories 'selection', 'comparability' and 'outcome'.The more stars, the better the quality of the article and the less chance of bias.Studies with seven or more stars were considered to be of high quality.The risk of bias was assessed by two reviewers.

| Characteristics of the 13 included studies
All studies had a nonrandomised prospective or retrospective design.28,31
All studies only included patients with symptomatic POP requiring apical surgical treatment.25]30 Exact preoperative staging is shown in Table 1.
Characteristics, inclusion and exclusion criteria, and outcome measures of the included studies are listed in Table S1.
Subjective outcome was measured with a validated questionnaire (PGI-I) in three studies. 25,27,28Five studies [19][20][21][22]24 defined subjective success as relief of prolapse symptoms b POP surgery includes: anterior repair, posterior repair, paravaginal repair, enterocoele repair. Thtotal amount of procedures can be higher than the number of patients because some patients received more than one concomitant procedure.c Studies with follow-up <12 months were excluded.

| Risk of bias
Figure 2 summarises the risk of bias. Figure 3 expresses risk of bias in percentages.Extensive information is available in Table S2.

| Results of primary outcomes
Tables 1 and 2 show an overview of the most important outcomes.Outcomes per study are shown in Table S3a,b.
Table 1 provides a combined overview of the data per outcome variable, number of reporting studies and total number of women.Table 2 shows the results of the pooled variables.
The pooled subjective cure rate was consistent between the two groups (93.1% for LUSLS-UP and 92.0% for LUSLS-HYS; Table 2).

| Complications
Table 3 shows an overview of all reported complications following a LUSLS procedure.No patients suffered from a Grade IV-V complication.The complication rate was 8% (95% CI 3.9-12.9).The majority of complications were mild (7%) (Clavien-Dindo I-II) and six were classified as Clavien-Dindo III, which resulted in a major complication rate of 1% (95% CI 0.5-1.9;Table 2).A statistical analysis of the difference in complications between LUSLS-UP and LUSLS-HYS was not possible due to reporting bias of minor complications.
Of the mild complications, the most frequently reported item was urinary incontinence; mostly described as 'de novo stress incontinence', which occurred in 21 of 303 patients (7%). 20,21,26,28,29One can argue about whether this should be interpreted as a complication; however, it is an impacting adverse event which we deemed important to show in this review.Other mild complications were urinary retention and urinary tract infections, which are seen frequently after POP F I G U R E 2 Risk of bias summary.surgery due to perioperative catheterisation.Pelvic pain (n = 12) and dyspareunia de novo (n = 2) have been described in seven studies; resulting in a prevalence of 3.4% and 0.7%, respectively.Other complications were very rare (Table 3).
No ureteral kinking, injury or obstruction was encountered in any the studies.
Six major complications were reported.Bladder injury occurred twice; 23,29 one during paravaginal repair. 23Both were discovered peri-operatively and repaired.One patient had a laceration of the left uterine artery as the suture was passed through the cervix, resulting in a large broad ligament haematoma.Conversion to laparotomy was performed and the patient received a blood transfusion. 22Another reported major complication was small bowel entrapment requiring laparotomy. 23Two patients underwent diagnostic laparoscopy in the month after surgery because of pain, 30,31 but no complication of LUSLS was encountered.

| Intervention details
The mean operating time for LUSLS procedures ranged from 22 to 120 minutes. 19,20,22,23,26In some studies, concomitant procedures were included in the operating time.Note: Meta-analysis (weighted average) of primary and secondary outcome measures; in the case of heterogeneity the random effects model was used; otherwise the fixed model was used.
Abbreviations: LUSLS-HYS, LUSLS with hysterectomy; LUSLS-UP, LUSLS with uterus preservation.a Fixed model was used because outcome was extracted from only two studies.
[26][27][28] Most studies report a median hospital stay of 1-2 days for all procedures (with or without hysterectomy), with one outlier of 4 days. 23

| Sexual function at follow-up
Five studies (276 women) have reported on sexual function at follow-up.In total, two women from a single study 28 experienced dyspareunia after LUSLS (0.7%).In the other studies, women with prior dyspareunia had improved sexual function after the procedure and no new cases of dyspareunia were described. 19,20,22,25

| Main findings
This systematic review presents an overview of the current literature laparoscopic uterosacral ligament suspension as a treatment for apical pelvic organ prolapse.The pooled anatomic success rate (defined as the total of women cured from apical prolapse ≥ stage 2) is 90% for all LUSLS procedures (95% CI 83.3-95.5)with a mean follow-up of 22 months.LUSLS combined with hysterectomy resulted in an anatomic success rate of 96.6% (95% CI 87.5-100) and LUSLS with uterus preservation a rate of 83.4% (95% CI 67.7-94.6).No significant difference was found.
The pooled subjective cure rate (defined as either satisfaction on the PGI-I scale or absence of POP symptoms) was 90.5% (95% CI 81.9-96.5).The subjective cure rates were the same after LUSLS-UP and LUSLS-HYS.LUSLS seems to be a safe procedure, as major complications were observed in 1% of the patients.

| Interpretation
Based on these results, LUSLS seems to equal other apical procedures in effectiveness and safety; however, other techniques have been studied in RCTs.Anatomic success rates of other apical surgical treatments vary widely in the literature.The most recent meta-analysis shows a success rate of 88-90% for SSF with a recurrence rate of 11%. 3 For both Manchester Fothergill and vaginal hysterectomy with McCall, the satisfaction rate was 89%. 33These rates are in line with the anatomic success rate of the LUSLS (90% overall, 83% UP and 97% LUSLS-HYS) and an apical recurrence of 10% that we found in this review.
Only the LSC seems to be superior according to the literature, with a success rate of 94% and recurrence rate of 6%. 3,28In a comparison of 103 women with LUSLS with 206 women with LSC, LSC scored significantly higher in objective and subjective cure rates and had fewer apical recurrences: 0% versus 12% after 22 months of follow-up.No difference was found regarding complications, postoperative pelvic pain, dyspareunia or de novo stress incontinence. 28 noteworthy finding is that no ureter obstruction or damage was encountered after LUSLS in the included studies.This is a complication of HUSLS, the vaginal high uterosacral ligament suspension (incidence of 1.8-9% 8,14,34 ).In the retrospective study of Houlihan et al. 8 (n = 206), comparing HUSLS and LUSLS, ureter kinking was found in 14 cases of HUSLS (9%), whereas none occurred in the LUSLS group (P = 0.023).The same result was found in the retrospective study of Turner et al.: 9 six cases of ureteral injury in the HUSLS group (5.0%) versus one case in the LUSLS group (1.9%).Moreover, women with LUSLS had a longer vaginal length (8.3 versus 7.4 cm, P < 0.001 9 ) and a higher subjective cure rate (76.2% versus 59%, P = 0.046 8 ) compared with HUSLS.No differences in anatomic results were found in either study. 8,9A large systematic review on HUSLS showed very high effectiveness (apical anatomic success in 98% after a mean follow-up of 25 months) and much lower numbers of ureter obstruction (n = 15; 1.8% 14 ) but it can lead to serious adverse events; in five cases, ureteral reimplantation was required.Our review confirms that ureteral kinking can be effectively avoided by the laparoscopic approach.However, for a fair comparison of HUSLS and LUSLS, a prospective trial is still needed, including a cost-effectiveness analysis.
Another vaginal option is the MF procedure, in which ureter problems occur very rarely (0.7% 35 ).However, a small study comparing the MF with MF + HUSLS showed better apical results after MF + HUSLS. 12It would be very interesting to compare MF directly with LUSLS.However, this would be a challenge, as one of the best indications for MF, cervical elongation, is a risk factor for failure in the LUSLS population when preserving the uterus.
In this review, de novo dyspareunia occurred in 0.7% of women (n = 2 19,20,22,25 ).Pelvic pain was present in 3.4% (n = 12 19,[28][29][30].Dyspareunia rates varies from 3% to 23% for other POP procedures.1,3,6,36 In summary, dyspareunia and pelvic pain rarely occurred and sexual function was not impaired by LUSLS. The available literature was not able to confirm whether LUSLS was suitable for recurrent POP surgery.In this review, most patients were treated for primary POP: only 9% had a history of POP surgery and this did not always involve the apical compartment.Most patients were treated for mild apical POP (Table 1, Table S3a,b).When interpreting the results of LUSLS, it is best to bear in mind that these success rates were achieved in a rather favourable population.
From our data we cannot give a recommendation regarding preservation of the uterus versus hysterectomy.No significant differences were found in anatomic/subjective success or recurrence rates after pooling data, but there was a trend towards more positive results after LUSLS-HYS (97% versus 83%).Bedford et al. 23 compared LUSLS-HYS (n = 160) with LUSLS-UP (n = 104) and showed higher failure rates in the uterus preservation group.Most failures in the uterus preservation group were associated with cervical elongation or uterine enlargement.We looked into the surgical technique of the LUSLS, but no differences in outcome were detected based on type and number of sutures, for example.Thus, no recommendations can be given regarding the best technique.Our recommendation would be to individualise and counsel women with the available information while awaiting further good quality research and longer follow-up results.
Apical procedures can have an effect on multiple levels of Delancy. 37The main goal of apical procedures is to restore level 1 support (the support of the apex of the vaginal vault or uterus,; e.g.uterosacral ligaments) but it can also have an impact on level 2 defects (in the anterior or posterior vaginal wall, e.g. the endopelvic fascia).The effect of LUSLS on level 2 defects was observed in three studies. 24,27,29In these studies, the anterior and/or posterior prolapse was lifted by LUSLS, without performing concomitant level 2 procedures.We advise peri-operative evaluation of the anterior and posterior compartment after LUSLS, as proceeding with concomitant surgery might not be necessary.

| Strengths and limitations
Strengths of this review are the large population and the ability to assess outcomes of LUSLS with or without uterus preservation.We included all studies with no restrictions on study design, number of participants or follow-up length; therefore, minimising selection bias and providing a complete overview of the existing literature.
This review has various limitations as well.There were no RCTs among the included studies; all of the studies had a retrospective or prospective design, and some studies were of low quality according to the Newcastle-Ottawa Scale.
We encountered statistical heterogeneity based on clinical diversity (difference in populations; primary or recurrent apical POP; stage of POP; difference in surgical technique) and methodological diversity (retrospective/prospective design, difference in follow-up length and outcome measures).This means we could not always draw conclusions about specific details of the LUSLS based on this meta-analysis; however, we were able to assess the LUSLS as an operation technique in a wider perspective and point out future research questions.
A point of discussion is the variety of subjective outcome.We pooled satisfaction and symptom scales to show subjective results, which is very important in the evaluation of a surgical procedure.Both scales are valid for subjective outcome, but from a point of view, we would have preferred not to combine this.
Exclusion bias in the sub-analyses of LUSLS-UP and LUSLS-HYS groups could not be avoided.In multiple studies, no distinction was possible between outcome of women with LUSLS-HYS, LUSLS-UP and LUSLS-VV.No original data were available from these studies; the authors were contacted but we did not receive any response.Therefore, we had to exclude these series 19,26,28,31 (n = 334) from the subanalyses (groups 2 and 3 in Table 1).

| CONCLUSIONS
The laparoscopic uterosacral ligament suspension seems to be a promising, effective and safe technique to treat apical pelvic organ prolapse, based on the current literature.It has clear advantages compared with other apical procedures: no mesh use (native tissue repair), low risk of ureter obstruction, a long total vaginal length and keeping the natural vaginal axis intact.Dyspareunia and pelvic pain are rare after LUSLS.Prospective and randomised controlled trials with long-term follow-up are necessary to confirm the efficacy and safety of this technique, including a cost-effectiveness analysis.This is also important to determine the place of the LUSLS for apical reconstruction compared with the other techniques.

AU T HOR C ON T R I BU T ION S
ALWMC, PRM-H and CKMV started with study planning, literature search and study enrollment.ALWMC and CKMV performed study screening and selected eligible studies, with PRM-H as third reviewer.BS performed the updated secondary search and final study enrollment, together with CKMV with ALWMC as third reviewer.BS and CKMV were responsible for the quality assessment, figures and tables.The article was written by CKMV.ALWMC checked the review for correct methodology.ALWMC, SALvL, JV and MBY assessed the study protocol and edited and reviewed the article.

AC K NO W L E D GE M E N T S
We would like to thank all of the authors of the included studies for sharing their series with us.Special thanks to the urogynaecology research team of Máxima Medical Centre for their advice and support throughout the process.Marta Regis, your statistical expertise was much appreciated and ensured a high-quality level of the meta-analysis.Thank you, Gwyneth Jansen, for checking the language and grammar of the paper.

F U N DI NG I N FOR M AT ION
None.

DATA AVA I L A BI L I T Y S TAT E M E N T
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

E T H IC S A PPROVA L
No ethical approval is required for this meta-analysis.

F I G U R E 3
Risk of bias graph.Review author's judgement about each risk of bias item presented as percentages across all included studies.T A B L E 2 Results of analysis.

T A B L E 3
Overview of described complications.

All studies LUSLS with uterus preservation LUSLS + Hysterectomy n/studies a Outcome n/studies a Outcome n/studies a Outcome
Outcome of the LUSLS.
T A B L E 1POP-Q stage ≥ 2 apical compartment preoperatively and at the end of follow-up period, n (%) Abbreviations: LUSLS-HYS, LUSLS with hysterectomy; LUSLS-UP, LUSLS with uterus preservation; LUSLS-VV, LUSLS on vaginal vault; POP, pelvic organ prolapse.a Number of participants and the number of studies reporting required data.