Comparison of outcomes between preservation or division of the uterine round ligament in laparoscopic groin hernia repair in females: a meta-analysis and trial sequential analysis

Purpose The purpose of this study was to perform a meta-analysis comparing the short-term and long-term outcomes in laparoscopic groin hernia repair with or without preservation of the uterine round ligament (URL) in females. Methods We searched several databases including PubMed, Web of Science, Cochrane Library, and and CNKI databases. This meta-analysis included randomized clinical trials, and retrospective comparative studies regarding preservation or division of the URL in laparoscopic groin hernia repair in females. Outcomes of interest were age, BMI, type of hernia, type of surgery, operating time, estimated blood loss, time of hospitalization, seroma, concomitant injury, mesh infection, recurrence, uterine prolapse, foreign body sensation, chronic pain, and pregnancy. Meta-analyses and trial sequential analysis were performed with Review Manager v5.3 and TSA software, respectively. Results Of 192 potentially eligible articles, 9 studies with 1104 participants met the eligibility criteria and were included in the meta-analysis. There were no significant difference in age (MD-6.58, 95% CI − 13.41 to 0.24; P = 0.06), BMI (MD 0.05, 95%CI − 0.31 to 0.40; P = 0.81), blood loss (MD-0.04, 95% CI − 0.75 to 0.66; P = 0.90), time of hospitalization (MD-0.22, 95% CI-1.13 to 0.69; P = 0.64), seroma (OR 0.71, 95% CI 0.41 to 1.24; P = 0.23), concomitant injury (OR 0.32, 95% CI 0.01 to 8.24; P = 0.68), mesh infection (OR 0.13, 95% CI 0.01 to 2.61; P = 0.18), recurrence (OR 1.13, 95% CI 0.18 to 7.25; P = 0.90), uterine prolapse(OR 0.71, 95% CI 0.07 to 6.94; P = 0.77), foreign body sensation (OR 1.95, 95% CI 0.53 to 7.23; P = 0.32) and chronic pain(OR 1.03 95% CI 0.4 to 2.69; P = 0.95). However, this meta-analysis demonstrated a statistically significant difference in operating time (MD 6.62, 95% CI 2.20 to 11.04; P = 0.0003) between the preservation group and division group. Trial sequential analysis showed that the cumulative Z value of the operating time crossed the traditional boundary value and the TSA boundary value in the third study, and the cumulative sample size had reached the required information size (RIS), indicating that the current conclusion was stable. Conclusion In summary, laparoscopic groin hernia repair in women with the preservation of the round uterine ligament requires a longer operating time, but there was no advantage in short-term or long-term complications, and there was no clear evidence on whether it causes infertility and uterine prolapse.


Introduction
Groin hernia is a prevalent condition in the field of general surgery, with a higher incidence rate among males.However, the occurrence of female groin hernia remains relatively low, with incidence of 0.3% [1].With the popularity of laparoscopic surgery, more and more women are undergoing laparoscopic groin hernia repair [2,3].The international guidelines for inguinal hernia management proposed by the HerniaSurge Group in 2018 recommend laparoendoscopic repair with mesh implantation for women with primary inguinal hernias [4].Due to the tight adhesion of the URL to the peritoneum, it is difficult to completely separate the URL in laparoscopic surgery, so the treatment of URL was controversial.Renshaw's study which included 1365 women with groin hernias who underwent traditional open surgery, laparoscopic surgery, and robotic surgery showed that there were no statistical difference in postoperative complications and recurrence rates between preservation and division groups, and they also found that the division group experienced less pain at 6 months than the preservation group [5].However, with the gradual proficiency of laparoscopic techniques and the deepening of the understanding of the function of URL, many experts began to prefer to retain URL [6].At present, there is a lack of multicenter, large sample size randomized controlled studies on the preservation of URL in female groin hernia surgery, and the preservation of URL often depends on the personal preference of the surgeon.We reviewed a lot of literature, and there is currently no meta-analysis on whether URL is preserved during laparoscopic groin hernia repair in females.Therefore, this paper will conduct a meta-analysis on the treatment of URL in laparoscopic repair of groin hernia in females, which will provide references for the treatment of URL by surgeons in the future.

Literature search
The databases of PubMed, Web of Science, Cochrane Library, Embase, and CNKI were searched respectively.Literature indexed from January 1, 1980 to June 1, 2023.The following search terms were used: "Female hernias", "Round ligament", "Round ligament of uterus", "Laparoscopic".

Inclusion and exclusion criteria
Inclusion criteria: (1) Studies in any language can be included; (2) Female patients undergoing laparoscopic groin hernia tension-free repair; (3) Randomized controlled or non-randomized controlled studies that reported age, BMI, operating time, estimated blood loss, time of hospitalization, seroma, concomitant injury, mesh infection, recurrence, uterine prolapse, foreign body sensation, chronic pain, pregnancy and other indicators.Exclusion criteria: (1) Abstracts, letters, expert opinions, systematic reviews and case reports are excluded; (2) Excluded studies that included traditional open surgery; (3) The studies of high ligation of hernia sac alone was excluded.The researchers first screened by title and abstract, and then screened by reading the full text.If studies are replicated, only the most recent studies were included.

Data extraction
Two researchers (ZW, FCF) independently extracted the following data from the included studies: first author, date of publication, study period, number of patients, country, study design, age, BMI, type of hernia, type of surgery, operating time, estimated blood loss, time of hospitalization, seroma, concomitant injury, mesh infection, recurrence, uterine prolapse, foreign body sensation, chronic pain, and pregnancy.If there was a disagreement during data collection, it would be resolved by a third researcher (ZWQ).

Assessment of methodological quality of included studies
On the basis of the standards described in the Cochrane Collaboration Handbook, risk of bias of studies contained in this review will be evaluated by all the authors [7].Disagreements between authors were resolved through discussion.

Statistical analysis
Meta-analysis was performed using Review Manager 5.2 (The Cochrane Collaboration, Oxford, UK).Heterogeneity was assessed using Cochran's Q test and I 2 statistics, and P < 0.1 was considered to indicate statistical significance.Sensitivity analysis was also performed by removing one study at a time and repeating the meta-analysis.Funnel plots were used to assess potential publication bias [8].
TSA was utilized to determine the required sample size for the meta-analysis and address the limitations of traditional meta-analysis.Some "positive" meta-analysis results may be attributable to random error; when the number of trials in a metaanalysis and the sample size of patients are small, random error may yield erroneous results [9][10][11].In this study, the researchers used the version 0.9.5.10 Beta TSA software to perform the analysis.The risk of type I and II errors was set to 5% and 20%, respectively.Concurrently, the alpha spending function, continuously monitoring boundaries, and evaluation of invalid boundary areas were estimated [12].

Study characteristics and quality
The 9 included studies were all from China, including 8 from mainland China and 1 from Hong Kong, 5 published in English and 4 published in Chinese, with sample sizes ranging from 34 to 393 (Table 1).The risk of bias summary is presented in Fig. 2.
There was no significant difference in time of hospitalization between the preservation group and division group (MD-0.22,95% CI-1.13 to 0.69; P = 0.64; Fig. 7).

Concomitant injury
3 studies reported concomitant injury as a complication indicator, including 163 patients (87 preservation group and 76 division group) [16,18,20], which could not identify heterogeneity and were analyzed using a random effects model.There was no significant difference in the concomitant injury rate between the groups (OR 0.32, 95% CI 0.01 to 8.24; P = 0.68; Fig. 9).

Uterine prolapse
3 studies provided data regarding uterine prolapse (279 preservation group and 253 division group) [16,17,19].There was high heterogeneity among these studies (I 2 = 71%, P = 0.03) and a random-effects model was used for meta-analysis.In the pooled data, there was no significant difference in the rate of uterine prolapse between the groups (OR 0.71, 95% CI 0.07 to 6.94; P = 0.77; Fig. 12).

Trial sequential analysis
Trial sequential analysis showed that the cumulative Z value of the operating time crossed the traditional boundary value and the TSA boundary value in the third study, and the cumulative sample size had reached the required information size (RIS), indicating that the current conclusion was stable ( Fig. 15).

Sensitivity analysis and publication bias
For each of the meta-analyses described above, similar results were obtained after removing each study individually (Table 2).For each of the meta-analyses, risk of publication bias was assessed using funnel plots, which did not indicate severe publication bias; as an example, the funnel plot for the meta-analysis of operating time is shown in Fig. 16.

Discussion
This study showed that there were no statistically significant differences in age and BMI between the two groups, indicating that the two groups were comparable.There were no significant differences in blood loss, time of hospitalization, seroma, concomitant injury, mesh infection, recurrence, uterine prolapse, foreign body sensation, and chronic pain between the two groups.In terms of operation time, the preservation group took longer, and the difference was statistically significant.The above results fully indicate that due to the close adhesion of URL to the peritoneum, it does take more time to completely separate the URL from the peritoneum in the operation.However, there was no difference in the short-term and long-term complications after the operation.Therefore, whether the URL should be preserved during the operation was indeed a question worthy of indepth discussion.The total length of URL is 12-14 cm.It starts from the anterior horn of uterus, the anterior lower end of the proximal fallopian tube, under the cover of the anterior layer of the broad ligament of uterus, runs anterolateral, passes through the opening of the internal ring and the inguinal canal, and ends at the anterior end of the labia majora        11 Forest plot comparing recurrence rates between the preservation group and the division group Fig. 12 Forest plot comparing uterine prolapse rates between the preservation group and the division group Fig. 13 Forest plot compares the occurrence of foreign body sensation between the preservation group and the division group Fig. 14 Forest plot compares the occurrence of chronic pain between the preservation group and the division group [22,23].It is composed of smooth muscle and connective tissue, and has no vascular distribution in it, which plays an important role in maintaining the forward position of the uterus [24].The URL is still an intraperitoneal organ at the corner of uterus, and gradually migrates into interperitoneal organs and extraperitoneal organs when it moves towards the opening of the internal ring [25].The URL here is tightly attached to the transverse fascia of abdomen, which is difficult to be separated.Therefore, the problem of how to deal with URL is bound to be faced in the operation of groin repair for female patients.
In the early stage of laparoscopic inguinal hernia surgery, the preservation of URL increases the difficulty of the operation and cutting URL does not cause serious complications, inadequate protection of URL has been common in female groin hernia repair for a long time [6].Due to the lack of understanding of the anatomy and function of URL, in the classic Shouldice procedure, the URL should be removed in order to close the inner ring.
As the function of URL is gradually being recognized, it is believed that its existence has its inevitable role.The reasons for preserving URL were as follows: (1) From the perspective of anatomy, the cut off URL will lose its role in maintaining the anteversion of uterus, and the retroposition of uterus can cause menstrual reflux, which is one of the causes of endometriosis [13]; (2) The cervix of the posterior uterus is raised, so that sperm can enter the uterine cavity is Fig. 16 Funnel plot of studies reporting on operating time difficult, which can cause infertility [13]; (3) It can prevent uterine prolapse, the URL is not only important in women of childbearing age, but also plays an important role in elderly patients.Its retention can not only prevent pelvic organ prolapse, but also serve as a fulcrum for surgical treatment when diseases such as pelvic prolapse occur [26,27]; (4) It has been reported that URL is not all tendinous structures, but contains muscular and tubular structures (lymphatic vessels) in the middle.Some scholars have confirmed that there was a far higher probability of edema of the labia majora after cutting URL.The reason may be that cutting URL will not only increase the local exudation, but also cause partial lymphatic reflux obstruction around the inner ring opening and the labia majora, resulting in increased flow in the surgical field and edema of the labia majora [1].Based on the above reasons, the significance of preserving URL cannot be ignored, especially for women of childbearing age.
On the other hand, there are also more scholars advocate cutting URL, mainly for the following reasons: (1) IEHS (International Endoscopic Hernia Society) guidelines also suggest that in order for the patch to effectively cover the fascia defect, the URL should be cut, so that the patch can cover the pectineus foramina in a smooth way, so as to achieve complete repair of the pectineus foramina and reduce the recurrence of oblique inguinal hernia [4,28]; (2) The peritoneum on the surface of URL is dense, so it is difficult to completely separate URL, which will cause postoperative bleeding and correspondingly prolong the operation time [13][14][15].
Whether cutting the URL increases the incidence of uterine prolapse was mentioned in only three studies in this meta-analysis.In Guo's study [16], the follow-up period was 24-90 months.Uterine prolapse occurred 5 patients in division group, but none in the preservation group.There was significant difference between the two groups.In Yan's study [17], the mean follow-up time was 42.9 ± 37.3 months, and 1 case of uterine prolapse occurred in the division group and 3 cases in the preservation group, with no statistically significant difference between the two groups.In Liu's study [19], the preservation group was followed up for 41.8 ± 24.2 months, and 4 cases of uterine prolapse occurred, while the division group was followed up for 42.7 ± 24.6 months, and 5 cases of uterine prolapse occurred, with no statistical significance between the two groups.In view of the fact that the occurrence of uterine prolapse requires a long follow-up time, the follow-up time of the above three studies is relatively short, and the conclusions are contradictory.Therefore, more studies with longer follow-up time should be included to draw more accurate conclusions.
Regarding the controversy about whether cutting the URL can cause infertility, few literatures have been reported, and only two studies have mentioned it [19,20].Due to the small amount of data, meta-analysis is not possible.Liu's study showed that after surgery, 14/218(6.42%) in the preservation group and 11/175(6.29%) in the division group had given birth or become pregnant, with an average follow-up of 41.8 months in the preservation group and 42.7 months in the division group [19].The proportion of women in the two groups had similar natural childbirth.Although fertility and natural delivery rates are affected by many factors, they suggest that cutting URL has little effect on fertility [19].Liang's study showed that 13 patients (61.9%) in the preservation group and 6 patients (30.0%) in the division group had fertility needs, of which 6 patients (46.2%) in the preservation group and 4 patients (66.7%) in the division group were successfully pregnant and gave birth [20].The results showed that there was no statistical significance in the fertility rate after surgery between the two groups [20].However, it should be noted that some patients in the group with preservation URL had a short follow-up time after surgery and some patients did not intend to become pregnant, and this part of patients needed to be observed after extended follow-up.Liang believes that the preservation of URL is one less factor affecting infertility for women in the fertile period [20].As far as the existing evidence is concerned, whether the preservation of URL has an impact on pregnancy or not, the results are not clear.We believe that for unmarried women who are not pregnant, the preservation of URL can be considered to avoid unnecessary trouble for patients.
The studies we reviewed were of relatively high quality.However, given some limitations, the results of our metaanalysis should be interpreted with caution.First, heterogeneity was found in meta-analyses of multiple variables (age, operating time, time of hospitalization, uterine prolapse and chronic pain), which may have reduced the reliability of these analyses, although we did compensate by using a random effects model.Second, some meta-analyses involve fewer patients, which may also affect their reliability.Third, only 3 randomized controlled studies were included.Fourth, all the included studies were Chinese studies, which may be biased.Fifth, despite an extensive literature search, we may have missed some unpublished studies.
In conclusion, laparoscopic groin hernia repair in women with the preservation of URL requires a longer operation time, and this systematic review and trial sequential analysis provide a conclusive evidence.Short-term or long-term complications were not significantly different between the two procedures, and there was no evidence that cutting URL caused infertility.More studies with longer follow-up were needed to draw more accurate conclusions about whether there was an increased incidence of uterine prolapse.Therefore, the author believes that for some unmarried women who are not pregnant, it can be considered to preserve URL, but these need to be further confirmed by larger prospective randomized controlled studies.

Fig. 2
Fig. 2 Risk of bias summary

Fig. 3
Fig. 3 Forest plot of age between the preservation group and the division group

Fig. 4
Fig. 4 Forest plot of BMI between the preservation group and the division group

Fig. 5
Fig. 5 Forest plot of operating time between the preservation group and the division group

Fig. 6
Fig. 6 Forest plot of blood loss between the preservation group and the division group

Fig. 7 Fig. 8
Fig. 7 Forest plot comparing hospitalization duration between the preservation and division groups

Fig. 9
Fig. 9 Forest plot compares the occurrence of concomitant injury between the preservation group and the division group

Fig.
Fig.11Forest plot comparing recurrence rates between the preservation group and the division group

Table 1
Characteristics of trials included in the meta-analysis