1 INTRODUCTION

Stress urinary incontinence (SUI) is a highly prevalent pelvic floor disorder, affecting approximately 46% of adult women, peaking at 50% in women 40 years and older.¹ It has been estimated that 10–14% of women will have an operation for SUI during their lifetime.^{2, 3} Mid-urethral sling (MUS) is widely regarded as the most efficacious method for surgical treatment of SUI.^{4, 5} For young women of reproductive age experiencing SUI, it has been suggested to delay surgical intervention until after completing childbirth due to concerns regarding the potential for SUI recurrence or complications during pregnancy or delivery.⁶ Moreover, caesarian section has been commonly proposed as route of delivery in case of pregnancy after MUS surgical implantation.⁷ Surgical treatment for SUI is less frequent among women under 40 years old compared to older women.⁸ However, there is a notable prevalence of severe SUI, reported to be around 10%, among women aged 25−49 years old.^{1, 9}

There is no guideline or clinical consensus concerning the MUS operation and future pregnancies, and the scientific evidence to substantiate any recommendation is scarce. Women who plan to become pregnant and give birth after undergoing an anti-incontinence procedure require thorough counseling regarding how pregnancy and various delivery methods can affect the likelihood of urinary incontinence (UI) recurrence. For that reason, we decided to perform a systematic review and metanalysis aiming to evaluate the impact of pregnancy and of delivery on SUI in women who previously sustained a MUS surgery.

2 METHODS

This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.¹⁰ The protocol was registered in PROSPERO (CRD42024497349).

3 RESULTS

3.1 Study selection

We identified 334 (EMBASE) and 79 (PubMed) studies (Figure 1). After checking for double results, and title, 36 articles were selected for abstract screening and 10 for text evaluation. Among these, 7 studies were selected for inclusion in the systematic review.^15-21

3.2 Risk of bias in studies and levels of evidence

The risk of bias analysis was performed for each study ranging from low to serious and it is summarized in Figure 2. The risk of bias analysis performed for the seven nonrandomized studies, showed that all seven studies had a moderate risk of bias.

3.4 Results of synthesis

The assessment of failure rate after delivery was reported subjectively as a dichotomous variable (yes/no) in all the studies. Two studies adopted validated questionnaires for the assessment of SUI recurrence: the Urogenital Distress Inventory (UDI) in one study¹⁸ and the Norwegian validated short-form urinary disease specific questionnaire in the other.²⁰ SUI recurrence was evaluated by Tulokas et al. by counting the number of visits for incontinence after delivery,²¹ while Cavkaytar et al. assessed SUI recurrence trough a cough stress test.¹⁶ The overall SUI recurrence rate was reported between the 18.0% and 26.0% with a pooled value of 22% in women who delivered after MUS surgery (Figure 3). The related I² test result was 0% demonstrating statistical homogeneity among studies. In 3 (3/7; 43%) studies women were not submitted to a new incontinence procedure for failure of SUI surgical treatment. SUI reintervention rate was between the 2% and the 8% with a pooled value of 5% (Figure 4); the related I² test was 47.34%, still showing statistical homogeneity among the included studies. Overall, most reported complications were UTI (range 0%−5.3%), voiding dysfunction (range 0%−5.3%) and persistent/de novo OAB/UUI symptoms (range 0%−54.0%). Vaginal erosion of the tape was not reported in any study. Pelvic or abdominal pain was reported in only one study in the 9% of cases (Table 3).²⁰

Table 3. Complications during and after pregnancy reported in the included studies.

Authors and year	Complications related to MUS, n (%)
Tulokas et al.21	UTI 4 (4.0) during pregnancy; Pain 12 (13.0) during pregnancy
Dyrkorn et al.20	UTI 2 (2.8) during pregnancy; Voiding dysfunction 1 (1.4) during pregnancy; persistent et de novo UUI 39 (54.0) after pregnancy
Bergman et al.19	Voiding dysfunction needing bladder catheterization during the pregnancy 3 (1.8)
Adams-Piper, Buono, et al.18	No complications
Adams-Piper, Darbinian, et al.17	No complications
Cavkaytar et al.16	No complications
Panel et al.15	UTI during pregnancy 1 (5.3); Renal colic during pregnancy 1 (5.3); Voiding dysfunction before and during pregnancy 1 (5.3)

• Abbreviations: MUS, mid-urethral sling; UTI, urinary tract infection; UUI, urgency urinary incontinence.

According to the metanalysis comparing women who delivered or not after MUS, three studies were included with 329 women who delivered (both vaginally and by caesarian section) after MUS and 860 women who did not deliver after MUS. SUI recurrence was not statistically different in the two groups (RR 1.01, 95% CI 0.73—1.40; p = 0.96), with a related I²—test of 41% (p = 0.18) (Figure 5) and in SUI reintervention (RR 1.45, 95% CI 0.91−2.30; p = 0.12), with a related I²—test of 0% (p = 0.38) demonstrating homogeneity among studies (Figure 6). Moreover, in MUS failure rate comparing delivery mode 6 studies with available data were included in the analysis. When data were available, women with SUI recurrence before pregnancy were excluded from the analysis; 131 women who had vaginal delivery and 163 women who had cesarian section were included. There was no difference between groups (RR 1.24, 95% CI 0.77−2.01; p = 0.37), with a related I²—test of 0% (p = 0.60) (Figure 7). Other risk factors for postpartum UI were a BMI ≥ 30 Kg/m², UI before and during pregnancy (Table 4). Concerning SUI reintervention, five studies were included in the study analysis with 124 women who delivered vaginally and 159 who were sustained a cesarian section. No differences were found between the two groups (RR 1.61, 95% CI 0.76−3.42; p = 0.22), with a related I²— test of 0% (p = 0.47) (Figure 8).

Table 4. Pooled results of factors associated with postpartum urinary incontinence from meta-analysis of cohort studies.

Risk factor	No. of studies	Case (n/N)	Control (n/N)	RR (95% CI)	I2 (%)	p Value
BMI ≥ 30 Kg/m2	2	41/111	107/644	2.21 (1.6, 3.0)	0	<0.0001
Parity ≥ 2	6	97/456	68/375	0.87 (0.4, 1.9)	74	0.74
Type of MUS	3	TOT 3/20	TVT 11/32	0.55 (0.2, 1.7)	0	0.31
UI before pregnancy	2	8/9	4/31	5.4 (1.1, 25.7)	63	0.03
UI during pregnancy	3	9/17	2/39	6.8 (1.8, 25.4)	0	0.004
Mode of delivery	6	VD 29/131	CS 29/163	1.2 (0.8, 2.0)	0	0.37

• Abbreviations: BMI, body mass index; CS, cesarian section; MUS, midurethral sling; RR, risk ratio; TOT, trans-obturator tape; TVT, Tension-free vaginal tape; UI, urinary incontinence; VD, vaginal delivery.

4 DISCUSSION

This systematic review and metanalysis aimed to evaluate the four main issues concerning the surgical management of SUI in young fertile women: (1) The recurrence rate and reintervention rate after childbirth in women previously submitted to MUS; (2) the risk of relapse of SUI and/or SUI reintervention related to childbirth; (3) the preferred route of delivery to prevent SUI relapse and/or reintervention; (4) safety in women who have pregnancy and childbirth after MUS surgery.

This metanalysis demonstrated a SUI recurrence rate of the 22% (95% CI: 18%−26%) and a SUI reintervention rate of the 5% (95% CI: 2%−8%) after childbirth in women previously submitted to MUS. Moreover, the results of this metanalysis showed that there is no difference in SUI relapse and reintervention between women who had childbirth after MUS procedure and women who did not have childbirth after MUS.

To date, an accepted definition of “young woman” lacks and we use to identify with this term women younger than 40 years-old and specifically those women who have not still completed their reproductive project. For this category of women there is not enough evidence about the consequence of pregnancy and delivery on the efficacy and safety of MUS implantation, and guidelines and recommendations supporting this decision making lack.

Lower urinary tract symptoms are a significant concern for women in all phases of life, including pregnancy and postpartum.²² Urinary disorders may reach the 97.3% of patients during all pregnancy periods, with increased frequency of urination, nocturia and urinary urgency reported as the most prevalent symptoms.²³ The prevalence of UI during pregnancy is reported ranging from 20% to 67%, with a tendency to worsen as gestation advances^{24, 25} and SUI prevalence is reported around the 40%.²³ All these considerations led physicians to retain that pregnancy itself and delivery could affect the results of anti-incontinence procedure.⁶ In addition, performing MUS at a young age may increase the risk of recurrence and the risk of long-term complications. Contrary to this hypothesis, the result of our metanalysis showed that MUS failure (RR 1.01, 95% CI 0.73−1.40; p = 0.96) and reintervention (RR 1.45, 95% CI 0.91−2.30; p = 0.12) for SUI relapse are not dependent from childbirth.

Moreover, in our study, the route of delivery did not affect the efficacy of MUS surgery. Indeed, we did not identify any difference between women who delivered vaginally and women who had cesarian section after MUS implantation both for SUI relapse (RR 1.24, 95% CI 0.77−2.01; p = 0.37) and for anti-incontinence reintervention (RR 1.61, 95% CI 0.76−3.42; p = 0.22). Considering that a successful MUS operation is thought to have a high risk of SUI recurrence if followed by pregnancy,⁶ many surgeons retain the caesarian section as the route of choice of delivery for pregnant woman after MUS.⁷ Even if we could not systematically distinguish all the indication for the caesarian delivery, it is likely that MUS has been the indication for several elective caesarian sections. In the included studies we showed a higher rate of caesarian section of the 43% up to the 66.7%; considering that vaginal delivery seems to not affect SUI relapse and reintervention, the mode of delivery should be decided on the base of obstetric indications.

A BMI ≥ 30 Kg/m², UI before and during pregnancy emerged as factors associated with postpartum UI in women who previously had MUS. Etiopathogenesis of SUI is known to be multifactorial, and in two of the three largest studies included in this systematic review^{19, 20} a BMI > 30 Kg/m² was highlighted as a risk factor for SUI relapse. Several risk factors, such as being overweight and obese,^{26, 27} cigarette smoking,²⁸ and maternal age²⁹ have been proposed for the development of UI^{23, 30} and should be considered for the management of SUI relapse after MUS procedure. Even if obesity is considered as an established risk factor for SUI,³¹ some studies presented conflicting results after MUS implantation.^{32, 33} In this field, the multifactorial etiology of SUI complicates the possibility of preventing SUI relapse. Anyway, patients with SUI submitted to MUS procedure should be educated about the advantages of maintaining a healthy BMI.

Additionally, this metanalysis observed that experiencing incontinence during pregnancy following MUS is correlated with postpartum incontinence. The data concerning the relationship between UI during pregnancy and its persistence or worsening postpartum are conflicting: Solans-Domenech et al.³⁴ found that UI during pregnancy is associated with postpartum incontinence, with vaginal delivery increasing the risk of persistent incontinence. Conversely, Wesnes et al.³⁵ concluded that the link between postpartum incontinence and mode of delivery is not significantly affected by incontinence status during pregnancy, and predicting a high-risk group for incontinence based on delivery mode cannot rely on continence status during pregnancy. According to our results, patients who develop UI during pregnancy after MUS should be counseled about the increased likelihood of this condition persisting after delivery and offered intervention if necessary.

Based on these observations, several studies tested the impact of childbirth on urinary continence in women who previously had MUS.^15-21

In the study by Tulokas et al.²¹ the authors concluded that pregnancy after MUS did not increase the odds for SUI re-procedure or re-visit and that future pregnancy does not need to be viewed as an absolute contraindication for MUS operation. This long-term retrospective case-control study adopted two Finnish national registers: the Care Register for Health Care (Care Register) and the Medical Birth Register. If on one hand these registries offered a substantial population-based sample without any selection bias, on the other hand it was not possible to detect recurrent SUI and other complications unless the women decided to seek help from a doctor, with a possible underestimation of UI relapse. The absence of an objective evaluation of UI at follow-up represent a limitation for this study.

Dyrkorn et al.²⁰ in their retrospective case-control study concluded that no differences in outcomes were seen between women who had childbirth and women who had not, independently of delivery mode. However, having more than one delivery after MUS seems to impact the continence status. Two Danish national registers, the National Norwegian Female Incontinence Registry and the Medical Birth Registry of Norway have been adopted and a validated short-form urinary disease-specific questionnaire for subjective data has been telephonically administered. As in the previous study, register offer a comprehensive long-term evaluation of the study population. However, UI have been only subjectively evaluated through the validated questionnaire, without an objective assessment such as urodynamics test.

The largest retrospective case-control study conducted by Bergman et al.¹⁹ concluded that childbirth subsequent to a MUS procedure does not carry an elevated risk of patient-reported SUI, and the continence status remains unaffected by the mode of delivery in the subsequent pregnancy. The study utilized nationwide Swedish health care registers to identify both cases and controls, while the UDI questionnaire was administered during follow-up. However, there was no objective assessment of SUI at follow-up. Additionally, the study did not provide information on continence status between MUS surgery and pregnancy, making it difficult to differentiate between pre-existing incontinence and that arising due to childbirth.

In 2016 and 2014, Adams-Piper and colleagues^{17, 18} concluded from their case-series that the safety and durability of MUS remained intact even after subsequent pregnancy, that vaginal delivery is not contraindicated and sling-related complications during pregnancy are not prevalent. However, the limited sample size and the absence of an objective assessment of SUI relapse during follow-up, including the lack of a clear definition for diagnosing SUI at follow-up, constrain the generalizability of the findings.

In their case series, Cavkaytar et al.¹⁶ concluded that the risk of postpartum SUI recurrence among women who have undergone MUS application appears to be consistent regardless of the mode of delivery, and data suggested that incontinence during pregnancy could potentially be a risk factor for postpartum incontinence. Although the small sample size may have hindered the reproducibility of these findings, the study conducted by Cavkaytar et al. stands out as the sole inclusion in this meta-analysis to utilize the stress test, providing an objective evaluation of SUI as per the study's objectives.

At last, the study by Panel et al.¹⁵ affirmed that pregnancy following surgical treatment for SUI with sub-urethral tape appears not to pose significant urinary or obstetric complications for patients. Pregnancy itself constitutes a risk factor for recurrent incontinence, and vaginal delivery did not elevate the risk of recurrence in comparison to cesarean section. However, the study design, the small sample size and the lack of a clear definition for diagnosing SUI at follow-up limit the possibility to spread recommendation related MUS in young women and route of delivery.

Presently, there is a lack of evidence-based data concerning the impact of subsequent pregnancy and delivery on the risk of SUI recurrence following a MUS procedure. In a survey conducted among members of the American Urogynecologic Society (AUGS), nearly 15% of respondents indicated that they would refrain from performing anti-incontinence surgery on patients planning future pregnancies. Additionally, 40% of respondents expressed a preference for cesarean delivery over vaginal delivery for patients who had undergone surgery for SUI.³⁶ AUGS reported that the available data are inadequate to determine whether recurrent rates of SUI vary between vaginal and cesarean deliveries.³⁷ According to the results of this metanalysis, childbirth does not increase the risk of SUI relapse after MUS surgery independently from the route of delivery.

Concerns about synthetic non resorbable materials vaginally implanted raised after several patients' class actions.³⁸ Specific tape complications, such as vaginal sling erosion, infection and chronic pelvic pain emerged, leading several national and international authorities to emanate recommendation for the use of synthetic non resorbable transvaginal tape and particularly MUS.³⁸ Consequently, some authors are persuaded that performing MUS procedures in the young may be associated with good initial outcomes, but with risk of long-term morbidity.³⁹ Moreover, MUS have been accused to lead to dyspareunia and sexual impairment. Indeed, when vaginal exposure of the polypropylene occurs in women submitted to MUS procedures, this may cause sexual dysfunction.⁴⁰ Moreover, vaginal MUS implantation itself may cause neurovascular tissue damages with sensory loss, pelvic pain, and dyspareunia.^40-42 For these several reasons, alternative less-invasive treatment as the urethral bulking agents (UBAs) have been proposed for young women affected by SUI.³⁹ Even if less effective than MUS on SUI,^{43, 44} UBAs showed a more important safety profile⁴⁴ and a good efficacy also in improving sexual function,^45-47 leading clinicians to consider the possibility of postponing MUS in favor of UBAs during reproductive age.³⁹ In the studies included in this systematic review, MUS did not show to increase complications both during pregnancy and at delivery. Indeed, the rate of complications possibly related to MUS such as UTIs and voiding dysfunction in pregnant women previously submitted to MUS is in line with that of pregnant women not previously submitted to MUS^{23, 48} at a long follow-up up to 129.6 months.

This systematic review and metanalysis has several limitations. All the included studies were retrospective reports with all the implicit defects of such design; however, MUS in young fertile women can be considered as a “rare condition.” Randomized controlled trials are not ethically possible for the evaluation of the optimal mode of delivery. Several studies presented a low sample size. Moreover, several missing data such as the assessment of SUI, birth weight, obstetric anal sphincter injuries, instrumental delivery, the obstetrician choice for the delivery route limited the possibility to perform metanalysis for these important sub-groups of patients. The number of studies ultimately included and analyzed in this meta-analysis was limited, primarily due to the majority of screened studies being of low quality. Moreover, the analyses were based on only three studies per comparison. Furthermore, the three population-based studies incorporated in this meta-analysis originate from a specific population in Scandinavia, which may restrict the generalizability of the findings to other regions. Therefore, adjustments of the presented data to suit the characteristics of the local population should be considered. However, we retain that this metanalysis presents several strengths too. We utilized prominent clinical literature databases from which data were extracted and analyzed employing rigorous statistical methodologies. The included population is a small population but of main clinical importance for several health care providers (urogynecologist, urologist, obstetrician etc.) that could confront this condition. This metanalysis has the largest overall sample size reported in the literature for this specific clinical issue, with all the included studies that showed homogeneous results. We deeply analyzed several potential risk factors related to postpartum relapse of UI. However, due to the inherent confounding effect in observational studies, these conclusions should be interpreted cautiously. Even if better design studies are needed, RCTs in this field are difficult and not ethically sustainable, making systematic reviews and metanalysis the main typology of research available to propose clinical recommendations.

5 CONCLUSION

The results of this metanalysis show that childbirth do not affect SUI relapse or reintervention in women previously submitted to MUS. Moreover, in the same population of patients, no difference where highlighted concerning the mode of delivery for the outcome SUI relapse or reintervention, and previous MUS surgery may not be an appropriate indication for caesarian birth in subsequent pregnancy. MUS does not increase complications in women who had childbirth after the anti-incontinence procedure at long term follow-up. Even if the results of our metanalysis does not highlight pregnancy, childbirth and mode of delivery as factors impacting MUS efficacy and safety, evidence are insufficient to make widespread recommendations.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.