Various therapies are currently used to treat symptoms related to the niche (an anechoic area) in the caesarean scar, in particular to treat abnormal uterine bleeding (AUB).
Various therapies are currently used to treat symptoms related to the niche (an anechoic area) in the caesarean scar, in particular to treat abnormal uterine bleeding (AUB).
To systematically review the available literature reporting on the effect of various therapies on niche-related symptoms.
A systematic search of MEDLINE, Embase, Cochrane, trial registers and congress abstracts from AAGL and ESGE was performed.
Articles reporting on the effectiveness of therapies other than hysterectomy in women with niche-related symptoms were included. Studies were included if they reported one of the following outcomes: effect on AUB, pain relief, sexual function, quality of life (QOL), and surgical, anatomic, fertility, or pregnancy outcome.
Two authors independently selected the articles to be included. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. A standardised checklist was used to score the methodological quality of the included studies.
Twelve studies were included, reporting on hysteroscopic niche resection (eight studies, 384 patients), laparoscopic repair (one study, 13 patients), (laparoscopic assisted) vaginal repair (two studies, 47 patients), and oral contraceptives (OCs) (one study, 11 patients). Reported AUB improved in the vast majority of the patients after these interventions, ranging from 87 to 100%. The rate of complications was low. Pregnancies were reported after therapy; however, sample sizes and follow-up were insufficient to study fertility or pregnancy outcome. The methodological quality of the selected papers was considered to be moderate to poor, and was therefore insufficient to make solid conclusions.
More evidence is needed before (surgical) niche interventions are implemented in daily practice.
Worldwide, the rates of caesarean section are rising. Caesarean section scars may be associated with complications in later pregnancies, such as uterine rupture, abnormally adherent placenta, and scar dehiscence or rupture.[2-5] The presence of an anechoic area at the site of a caesarean section scar has been observed in women after a caesarean section. In random populations, it was present in 24–69% of women evaluated with transvaginal sonography (TVS), and in 56–78% of women evaluated with transvaginal sonohysterography (SHG).[6-12] Such an anechoic area is also known as a niche (Figure 1).[6, 8, 9, 13, 14] A generally accepted definition of a niche is still the subject of debate, however.
A common symptom reported to be associated with the presence of a niche is postmenstrual spotting. The first publications on caesarean section scar defects in relation to bleeding symptoms date from 1975. Since then many articles have reported a high prevalence of niches in women with abnormal uterine bleeding (AUB), including prolonged menstruation or postmenstrual spotting (PS).[9, 14, 17-21] Two studies reported a significantly higher prevalence (34 and 29%) of postmenstrual spotting in women with niches compared with women who did not have niches during SHG (OR 2.8 and 5.5) in a random population of women with a history of caesarean section.[6, 12] One other study reported a higher prevalence of postmenstrual spotting in women after a caesarean section than after vaginal delivery, but could not identify a significant relationship with the existence of a niche. The same study did, however, report a higher frequency of AUB in women with diverticula (anechoic round structures) and deformation of the cervical canal at the scar site, identified during TVS. Postmenstrual spotting after a caesarean section in women with a niche is not a rare event. Approximately 60% of women have a niche after a caesarean section, and of these approximately 30% experience postmenstrual spotting.[6, 12] Other reported symptoms in women with a niche were dysmenorrhea (53.1%), chronic pelvic pain (36.9%), and dyspareunia (18.3%).
It has been assumed that AUB may be caused by the retention of menstrual blood in the niche, which is intermittently expelled after menstruation has almost completely ceased, causing postmenstrual spotting and pain.[4, 17, 22] The presence of fibrotic tissue below the niche may impair the drainage of menstrual flow. Additional, newly formed fragile vessels in the niche may also contribute to the accumulation of blood produced in situ.
Niche-related menstrual bleeding disorders do not always respond to hormonal therapies. Therefore, a hysterectomy is often performed to treat niche-related gynaecological symptoms.[17, 25, 26] In women who wish to preserve their fertility, however, less invasive, more conservative treatments have been developed. These therapies aim to: facilitate the drainage of menstrual blood and to reduce the in situ production of blood by coagulating niche vessels (hysteroscopic resection);[22, 24, 27-29] reconstruct the uterine defect in the caesarean section scar [abdominal, (robotic) laparoscopic, or vaginal repair];[30-37] reduce menstrual periods (continuous hormonal therapies); or reduce menstrual blood (cyclic hormonal therapies or other medical therapies). Before surgical interventions such as niche resections or niche repair are implemented on a large scale, their effectiveness should be proven and compared with medical therapies or expectant management.
The objective of the current review is to provide an overview of the available literature on the effect of niche therapies, except for hysterectomy, on AUB and other gynaecological symptoms, including surgical, anatomical, and fertility outcomes.
We performed this systematic review according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines, as all of the studies included were observational.
The MEDLINE, Embase, and Cochrane computerised bibliographic databases were searched. Also the following trial registers, www.clinicaltrial.gov and www.trialregister.nl were searched for continuing or not yet published studies. To avoid missing recent and not yet indexed studies, the 2012 annual abstract compilations by ESGE and AAGL were checked. The search was performed within the following limits: reports in English, and published between 1 January 1950 and 15 August 2013. The search strategy was developed with the assistance of a research librarian specialised in medical sciences, and included the following terms appearing in the title, abstract, or keywords: treatment (medical subject heading, MeSH), surgical procedures, operative (MeSH), caesarean section (MeSH), uterus, cicatrix, scar, isthmocele, niche, pouch, wound dehiscence, diverticula, and scar defect (Appendix S1). The reference lists of retrieved articles were cross-checked for relevant studies.
All randomised controlled trials, cohort studies, case–control studies, and case series of at least five patients were considered for inclusion if they: (1) reported on conservative therapies (hysteroscopic niche resection, laparoscopic repair, abdominal repair, vaginal repair, endometrial ablation, levonorgestrel intrauterine system, or medical treatment) for the treatment of niche-related symptoms in non-pregnant patients; and (2) reported on one of the following outcomes – AUB, pain relief, sexual function, quality of life (QOL), surgical outcome, and anatomic reconstruction, fertility, or pregnancy outcomes. All other studies (including case reports and video reports) were excluded.
For reports that were published twice we included the study with the largest number of included patients. An eligibility assessment was performed independently in an (unblinded) standardised manner by two reviewers trained in performing systematic reviews (L.V. and J.H.). Disagreements between reviewers were resolved by having three reviewers (L.V., J.H., and A.V.) review the original article until a consensus was reached.
Data extraction was performed according to a standardised format including items about the general study level characteristics (such as design, population, and setting), diagnosis, the intervention studied, and the outcomes. To get an impression of the quality of the included studies, all studies were systematically evaluated on possible bias (selection bias, verification bias) and a structured checklist was used with the following items: clear definition of primary outcome; (validated) instruments used for measurement outcome; clear definition of population; clear definition of the inclusion and exclusion criteria; clear definition of niche and of niche measurements; evaluation pre- and post-treatment similar regarding diagnosis of niche and bleeding outcomes; clear methods of follow–up; and reporting on non-treated patients and complications (Tables 2 and 3). Every included study was evaluated by two reviewers independently (L.V. and J.H.). Data in the tables are subdivided according to the type of intervention.
To study the effect on postmenstrual bleeding, a meta-analysis was performed by use of comprehensive meta-analysis 2, (2005; Biostat, Englewood, NJ, USA). Results were presented in a forest plot, comparing outcomes after therapy with baseline.
The electronic search in MEDLINE, EMBASE, and Cochrane generated 1861 records. Two additional records were identified through cross-checking and 244 additional records were identified in the trial registers. Two continuing studies were identified, with no data yet reported: one prospective cohort and one randomised controlled trial (NTR 3269 and NTR 1922). After the removal of duplicates, 1629 records were screened, and 28 articles were thought to meet the inclusion criteria and were selected for full article assessment. An additional 16 articles were excluded because of the following reasons: study design (six case reports, five video reports); two double publications; two that included other subjects; and one review without original data. Ultimately, 12 studies from eight countries were included in this review (Figure 2). The studies, 11 peer-reviewed articles,[22, 24, 27-29, 35, 37, 38, 41-43] and one abstract, were published between 1996 and 2013, and reported on a total of 455 women (Table 1).
|Author year||Design||Period||n||Intervention (n)||Follow-up (months)||Control (n)||Indication||Primary outcome||Secondary outcomes|
|Hysteroscopic niche resection|
|Chang||Prosp. cohort||2005–2008||57||hys. resect. (22)||NR||None||PAUB||NR||NA|
|Gubbini||Case series||2005–2008||41||hys. resect. (41)||NR||None||PAUB||Infertility||NA|
|Gubbini||Case series||2001–2005||26||hys. resect. (26)||NR||None||PAUB||PAUB||Infertility|
|Marra||Case series||2001–2009||78||hys. resect. (78)||NR||None||PAUB, HMB||PAUB||Infertility|
|Feng||Retro. cohort||2006–2009||62||hys. resect. (57)||12||None||PAUB, PM||AUB||NA|
|Wang||Retro. cohort||2003–2008||57||hys. resect. (57)||45||None||PAUB, PM||AUB, DM||Prog fact.|
|Fabres||Retro. cohort||1993–2001||24||hys. resect. (24)||14–24||None||PAUB||AUB||Infertility|
|Florio||Case–control||2007–2009||39||hys. resect. (19)||3||OC/20||PAUB||AUB, DM||Satisfact.|
|Laparoscopic niche repair|
|Marotta||Case series||NA||13||lap. repair (13)||3–48||None||RM <3 mm||Uterine anat. RM||Pregnancy outcome|
|Vaginal niche repair|
|Klemm||Case series||1999–2004||5||vag. repair (2) lap. vag. (3)||30 (3–46)||None||AUB, pain||Uterine anat.||Pregnancy outcome|
|Luo||Retro. cohort||2010–2011||42||vag. repair (42)||10–23||None||AUB, PAUB, PM||Uterine anat.||NA|
|Tahara||Case series||1997–2003||11||OC (11)||12||None||PAUB||PAUB||NA|
Large randomised controlled trials are lacking. Three studies were reported as prospective cohort studies; however, based on the reported methodology we qualified them as case series.[24, 28, 45]
None of the articles met all of our quality criteria. A clear definition and standardised measurements of outcomes were lacking in most articles. Most studies did not report how they evaluated bleeding symptoms or niche measurements. None of the studies reported on the use of validated instruments (Table 2).
|References||Clear definition of primary outcome||Clear instrument (validated) to measure primary outcome||Clear description of population||Definition of niche/ minimal size for diagnosis||Clear description of inclusion criteria||Clear definition of exclusion criteria||Evaluation pre- & post-treatment similar (bleeding)||Evaluation pre- & post-treatment similar (niche)||Follow-up period defined||Complete follow-up||Outcome of non-treated patients||Complications reported|
|Hysteroscopic niche resection|
|Wang||Yes: days of menstruation||NR||No||Yes/NR||No||Yes||NR||No||NR||NR||NA||Yes|
|Laparoscopic niche repair|
None of the included articles described efforts to address potential sources of bias or confounding. For example, the method of patient selection and enrolment were not reported. Data on excluded patients, those lost to follow-up, or missing data for outcome measurements are lacking. Methods of post-treatment outcome measurements were not reported or were different from pre-treatment evaluation in most studies, indicating a high risk of verification bias (Table 3). Publication bias is suspected because there were only articles with positive effects and small sample sizes, and large randomised trials and prospective cohort trials are lacking.
|References||Risk on selection bias||Risk on verification bias|
|Chang||Low||Clear definition of population, and inclusion and exclusion criteria||NA||Evaluation post-treatment not reported, no information on follow-up|
|Gubbini||High||No clear population, no clear exclusion criteria, only patients with pregnancy after therapy included||Low–moderate||No clear definition of outcomes; however, biopsy taken but possibly not relevant|
|Gubbini||High||No clear population described, no clear in/exlusion criteria, no information on excluded patients||Low–moderate||No clear definition of outcomes; however, biopsy taken but possibly not relevant|
|Marra||High||No clear description of population, no clear in/exclusion criteria, no clear outcome||Low–moderate||No clear definition of outcomes; however, biopsy taken but possibly not relevant|
|Feng||Moderate||Clear description of population but no clear definition of niche||NA||Evaluation post-treatment not reported, no information on follow-up|
|Wang||High||No clear inclusion criteria and population description||High||Different methods of evaluation pre- and post-treatment|
|Fabres||Moderate||No clear inclusion criteria||NA||No information on post-treatment evaluation|
|Florio||High||PAUB not defined, no clear population described, no information on criteria for treatment options||High||Different evaluation for treatment groups; different evaluation pre- and post-treatment|
|Marotta||High||Population not described, no clear definition of niche||Low|
|Klemm||High||No clear population described, no clear in/exclusion criteria||Moderate||Incomplete follow-up|
|Luo||High||No clear population described, no clear in/exclusion criteria, PAUB not defined||Low|
|Tahara||Moderate||PAUB not defined, clear population||NA||Evaluation post-treatment not reported|
Reported interventions were hysteroscopic niche resection (Figure 3),[22, 24, 27-29, 42, 43, 45] laparoscopic niche repair, laparoscopic assisted vaginal repair, vaginal repair (Figure 4), and oral contraceptives. Details about the technical aspects are given in Table 4.
|References||Intervention||Duration of surgery (min.)||Success of therapy||Admission Hospital (days)||Anesthesia applied||Type of hysteroscope||Distension medium||Safety check during surgery||Compli- cations|
|Hysteroscopic niche resection|
|Chang||Distal, coag. loop||NR||100%||NR||NR||9 mm mon.||Sterile water||US||None|
|Gubbini||Dist. & prox., coag. rollerball||14.1 (± 3.5)||100%||NR||General||9 mm mon. Storz||Glycerine/manitol||M-blu||None|
|Gubbini||Dist. & prox., coag. rollerball||NR||100%||NR||NR||9 mm mon. Storz||Sorbitol/manitol||M-blu||None|
|Marra||Dist. & prox., coag. rollerball||NR||100%||NR||NR||9 mm mon Storz||Sorbitol/manitol||M-blu||None|
|Feng||Distal, coag. rollerball||NR||92% (57/62)||NR||General||6.5 and 8 mm bipol.Olympus||5% manitol||None||None|
|Wang||Distal, coag. rollerball||30.2 (±6.6)||100%||Outpatient||NR||26F Storz resectoscope||Distilled water||None||None|
|Fabres||Distal, coag.||NR||100%||NR||NR||9 mm mon. Storz||Sorbitol/manitol||None||None|
|Florio||Dist. & prox., coag. rollerball||NR (only for subgroups)||100%||NR||General||NR||Sorbitol/manitol||None||None|
|Marotta||Cut out, two-layer closure||NR||100%||<1||General||Nonea||Hyster.||None|
|(Laparoscopic assisted) vaginal repair|
|Klemm||Cut out, one-layer closure||117 (27–92)||100%||NR||NR||NA||NA||TVU||None|
|Luo||Cut out, two-layer closure||55.3 (± 23.5)||100%||4 (±2.1)||NR||NA||NA||None||2.4%b|
|Tahara||oral contraceptive (ethinyl estradiol/norgestrel)||NA||NA||NA||NA||2c|
The use of OCs in the treatment of niche-related AUB was studied in two studies.[38, 42] Women used OCs for 21 days followed by 7 days of OC withdrawal in both studies. The OCs contained 0.5 mg norgestrel and 0.05 mg ethinyl-estradiol, or 0.075 mg gestodene and 0.030 mg ethynylestradiol.
There were no reports on abdominal interventions, levonorgestrel intrauterine system (IUS) or endometrial ablation that met our selection criteria.
All studies included women with a niche identified via TVS, hysteroscopy, or magnetic resonance imaging (MRI). Three studies did not provide a definition of a niche. Excepting one study, none of the studies provided an objective reproducible method of niche measurement for inclusion. Only Marotta used an objective cut-off level for inclusion. All studies, except two, included women with AUB, in particular postmenstrual AUB. Two studies also included women without symptoms, because of the presence of a large niche and a desire to maintain fertility (Appendix S2; Tables 1, 2 and 4).[35, 41]
All of the studies included reported on women with AUB (n = 455); nine reported specifically on postmenstrual spotting (Appendix S2). None of the studies used validated questionnaires to assess bleeding disorders. Four studies did not report any quantitative outcome with respect to AUB.[22, 37, 41, 45] AUB was reported to be improved in 87% (hysteroscopic resection),[22, 24, 26-29, 42, 43, 45] 100% (laparoscopic repair), 93% (vaginal repair), and 91% (OCs) of women. Three studies, including 121 women, reported on bleeding parameters both at baseline and after surgery: hysteroscopic niche resection reduced the number of days of bleeding by 2–4 days,[27, 43] and vaginal repair reduced the number of days of bleeding by 4–7 days. These three studies reported sufficient data for evaluation in a meta-analysis. The weighted mean difference was –4.48 days (95% CI −6.59 to −2.37 days; Figure 5). A retrospective study comparing the reduction in menstrual bleeding after hysteroscopic niche resection with OCs was in favour of the hysteroscopic niche resection: the reduction of menstrual bleeding was 2.5 days more after hysteroscopic niche resection.
Data on pain were reported in three studies, including 93 women.[29, 37, 42] At baseline, 38–63% of these patients reported pain. After hysteroscopic resection pain symptoms were reported to be resolved in 97% of the patients and in 100% of the patients after laparoscopic repair (Appendix S2). Data on methods of pain assessment are lacking.
The reported satisfaction rates regarding relief of bleeding symptoms were: 87% (range 59–100%) after hysteroscopic resection (310 patients);[22, 24, 27-29, 43, 45] four out of four patients after laparoscopic repair; 45 out of 47 patients after vaginal repair; and ten out of 11 patients after treatment with OCs (Appendix S2). No validated questionnaires or other validated tools were used to asses urinary symptoms, sexual function, or QOL. Additional therapies applied because of the failure of the initial methods were reported in two studies.[28, 37] Ten women received additional OCs and one underwent a hysterectomy after hysteroscopic niche resection. One woman underwent a second vaginal repair after the failure of the first.
The success rates reported after surgery were 92–100% after hysteroscopic resection,[22, 24, 27-29, 41, 43, 45] and 100% after laparoscopic and vaginal repair.[37, 41] Four studies included a diagnostic hysteroscopy 8–12 weeks after hysteroscopic surgery for the evaluation of uterine and niche anatomy; however, detailed information on the criteria used and the outcomes is lacking.[24, 28, 29, 42] Direct endometrial biopsy confirmed the presence of cuboid endometrial cells covering the niche after 8–12 weeks in 60 out of the 60 women evaluated.[29, 42]
The mean thickness of the residual myometrium after laparoscopic repair increased by 8.2 mm, as measured on MRI, after a mean follow-up period of 3 months (Appendix S3).
No complications or adverse effects were reported after hysteroscopic resection or laparoscopic repair. Reported side effects in two of the 11 women treated with OCs included breast tenderness and nausea. After vaginal repair, an infection was reported in one of the 42 treated patients (Table 4).
Seven studies reported on fertility and pregnancy outcomes. A total of 78 women were reported to have fertility problems, of whom 72 later conceived (92%): 67 after hysteroscopic resection, four after laparoscopic repair, and one after vaginal repair (Appendix S4).[21, 23, 27, 28, 34, 40, 44] Four of the 72 pregnant women had a spontaneous miscarriage, and 58 women delivered at term by a planned caesarean section. The pregnancy outcomes for an additional ten pregnant women were not reported. No additional obstetric complications were reported. The duration of subfertility and details on previous diagnostic work-up in relation to the therapies received was reported in one study. This study included 41 subfertile women, all with fertility problems of unknown aetiology and with a duration of more than 2 years. All were reported to have conceived within 2 years without additional therapy. After vaginal repair or medical treatment, no information on pregnancies was reported.
The effect of therapy on bleeding symptoms or other gynaecological symptoms could be evaluated in 384 women after a minimally invasive surgical intervention, and in 31 women after OC therapy; however, the methodological quality of the majority of papers included should be regarded as moderate to poor. The included studies reported a reduction of AUB and pain and a high rate of satisfaction among most women after hysteroscopic niche resection or vaginal or laparoscopic niche repair. A significant difference was reported using a meta-analysis on AUB after treatment compared with baseline. The thickness of the residual myometrium after laparoscopic niche repair increased substantially. Quality of life, sexual function, and urinary symptoms were not studied. Seven studies reported on pregnancy outcomes without an adverse outcome in 52 women after hysteroscopic niche resection, in three women after laparoscopic niche repair, and in one woman after vaginal niche repair.
We included only articles published in English and we excluded case reports, which involves a risk of reporting bias. As a consequence we may have missed relevant publications or rare complications. In general, a funnel plot could be helpful to assess the level of publications bias; however, only three observational studies reported sufficient data to be included in a funnel plot, and as a consequence this will not provide reliable information.[46, 47] We used a structured checklist in an attempt to weight the scientific quality of included studies; however, this review was hampered by the fact that several of the individual studies did not report all relevant information needed to do this in a proper way. Clear definitions of primary outcome, abnormal uterine bleeding, abnormal postmenstrual bleeding, pain, satisfaction, or a successful procedure are lacking. Validated instruments for the measurements of these outcomes were not used.
Most studies do not report the method of patient enrolment, the number of excluded patients, or the number of patients lost to follow-up; therefore, besides selection bias, verification bias cannot be excluded. In addition, the sample size in most of the included studies is insufficient to draw solid conclusions, in particular with respect to fertility or pregnancy outcome or to enable the eventual correction for confounding. Long-term outcome after various therapies is not reported in most studies, so information on the risk of recurrence cannot be addressed. Although many studies reported a high success rate for the procedure they examined, none underscored their statements or conclusions with data. It is surprising that none of the studies assessed the effect of the interventions on patient QOL. Only seven studies reported on pregnancy outcome after hysteroscopic niche resection or laparoscopic repair. These women were all scheduled for an elective caesarean section, so the success rate for trial of labour after various niche therapies cannot be addressed.
As far as we are aware only one review has previously been published on this topic, which reported on the effect of hysteroscopic niche resections on fertility outcome. That review concluded that hysteroscopic niche resection was effective in improving symptoms related to menstruation, and that it restored fertility in a high percentage of women treated; however, they did not perform a systematic literature search and did not perform a critical appraisal.
Given the methodological shortcomings of the included studies in this review we have to conclude that the current evidence is not sufficient to draw solid conclusions on the effectiveness of the interventions under study. And as a consequence, the outcomes of our meta-analyses to assess improvement of bleedings symptoms should be critically assessed. In addition, the number of pregnant patients is insufficient to analyse pregnancy outcomes or to estimate the risk of pregnancy-related complications after hysteroscopic niche resection or laparoscopic niche repair. Although the thickness of the residual myometrium (RM) increased after laparoscopic niche repair and the majority of the patients had an RM of over 8.3 mm after therapy, it is unknown what this means for the risk of uterine rupture. We do not know if an increased thickness of the RM is related to an improved functionality of the lower uterine segment. In addition, we do not know the effect of hysteroscopic niche resection on the risk of uterine rupture, malplacentation or cervical incompetence. In theory one could assume the hysteroscopic resection reduces the thickness of the residual myometrium and its functionality; however, information on this topic is currently lacking. Some studies reported on a laparoscopic (assisted) niche repair in asymptomatic patients.[31, 41] Given the lack of information of the effect of surgical interventions on pregnancy outcome, we believe that these interventions should only be considered in symptomatic patients. This was also stated by Demers and colleagues The effect of OC on niche-related bleeding symptoms was assessed in only two studies, with a total of only 31 patients.[38, 42] Given the high rate of successful levonorgestrel IUS insertions for abnormal uterine bleeding, it is surprising that its effect on niche-related AUB has not yet been evaluated.
Because of the dearth of comparative studies of sufficient methodological quality, evidence on the most optimal therapy is lacking. In view of the lack of evidence, the least invasive therapy, i.e. OC, should be considered the first choice for the treatment of gynaecological symptoms. This is of course less suitable for women who desire to conceive in the short term.
Given the lack of sufficient evidence on the outcome of hysteroscopic, laparoscopic, and vaginal repair on fertility and pregnancy outcome, we propose that these interventions should only be applied in a research setting with long-term follow-up.
The included studies report a reduction of AUB, a substantial reduction of pain or prolonged bleeding, and a high rate of satisfaction in most patients after hysteroscopic niche resection, or vaginal or laparoscopic niche repair, with a low complication rate; however, concern about the methodological quality of the included studies exists. Because of the small sample sizes and incomplete long-term follow-up no conclusions can be drawn on the risk of complications during pregnancy or delivery after these therapies. Comparative studies of different therapies with sufficient methodological quality are lacking. Future studies that include a sufficient sample size, with long-term follow-up and using validated instruments, are needed. Surgical interventions should be compared with expectant management or medical therapies, including levonorgestrel IUS. Until this information is acquired surgical niche therapies should only be applied in a research setting, preferably in randomised trials.
None of the authors have relevant financial, personal, political, or religious interest linked to the subject of this article.
The review was conceived by L.V., A.V., and J.H., and they selected the articles and collected the data. Analysis of the data was performed by L.V. and J.H. The first draft was written by L.V. and J.H., and A.V., M.B., H.B., and S.V. supervised the article to the final draft.
Ethics approval was not needed because this is a literature study.
This study is funded by ZonMw, The Netherlands Organization for Health Research and Development (project no. 80-82305-97-12030).
We thank Mrs Boerstoel, assistant librarian, for her help with the literature search.