Correspondence to Jolijn Vissers; [email protected]
STRENGTHS AND LIMITATIONS OF THIS STUDY
This study is a randomised controlled trial to evaluate the effect of laparoscopic niche resection in comparison to expectant management on reproductive outcomes in infertile women with a large uterine niche.
In line with the Idea, Development, Exploration, Assessment and Long-term study framework, was the trial designed after optimalisation of the surgical procedure and completion of the learning curve.
The trial is large and powered to assess time to ongoing pregnancy.
Laparoscopic niche resection is in the Netherlands currently not offered as a part of usual care, which reduces the risk on selection bias.
It is an open-label trial, which may affect the outcomes reported by the patients.
Introduction
Caesarean sections are rising worldwide.1 The increasing caesarean section rate has raised an interest in the potential long-term sequelae of caesarean scarring. A uterine niche is a defect in the myometrium at the uterine caesarean section scar site; the phenomenon has been described frequently in recent years.2–6 A uterine niche is formally defined by the international Niche Taskforce as ‘an indentation at the site of the caesarean scar with a depth of at least 2 mm’, visible by means of transvaginal ultrasound (TVUS).7 Previous studies have shown that, in approximately 50%–60% of women with a history of a caesarean section, a niche can be visualised during sonohysterography.2 8 9 Uterine niches are associated with gynaecological symptoms such as postmenstrual spotting, dysmenorrhoea and chronic pelvic pain.2–4 9 10
A uterine niche may also reduce fertility.11–14 A meta-analysis reported that a caesarean section on average reduced the probability of a subsequent pregnancy by 10% (relative risk, RR 0.91; 95% CI 0.87 to 0.95), relative to a vaginal delivery.15 None of the studies included in this meta-analysis evaluated the relationship between subsequent fertility and the presence of a uterine niche. Theoretically, the accumulation of blood, mucus and fluid in the niche and uterus may impair the penetration of sperm cells and the implantation of embryos.9 16 17 Sometimes, when combined with an extremely retroverted uterus, a (large) niche may hamper the insertion of an insemination or embryo transfer catheter.17 A recent study including 1307 women undergoing their first IVF cycle reported significantly lower live birth rate in women with a previous CS compared with women with a previous vaginal delivery (OR 0.63, 95% CI 0.45 to 0.87).12 Also, in this study, the presence of a niche was not always reported. A recent large prospective cohort study (n=4879) that evaluated the effect of the presence of a niche on reproductive outcomes after single embryo transfer and that corrected for potential confounders such as age, body mass index, fresh or frozen-thawed cycle, the stage of embryo at transfer and endometrial thickness, showed a significant lower live birth rate and higher miscarriage rate in women with a niche compared with women without a niche (aOR 0.61, 95% CI 0.47 to 0.78 and aOR 1.41, 95% CI 1.03 to 1.9). The differences in live birth rate were even larger if the presence of a large niche was compared with the presence of a small niche (aOR 0.42, 95% CI 0.20 to 0.90).14 These study results indicate an intermediate role of a niche in the lower pregnancy and live birth rates after a CS compared with a vaginal delivery.
In the past 15 years, several innovative surgical procedures have been developed to treat niche-related symptoms.18–27 Laparoscopic treatment was first described in 2003.28 A hysteroscopic niche resection is effective in reducing spotting symptoms in women with small niches, but does not restore the anatomy.29 A laparoscopic or vaginal niche resection aims to reduce symptoms, restore the anatomy and increase the thickness of the residual myometrium (see figure 1A,B). The latter procedures are suitable for women with large niches with thin residual myometrium.24
Enlarge this image.Figure 1. Image of a niche in midsagittal plane using transvaginal ultrasound before (A) and after (B) laparoscopic niche resection in the same women. (A) Extremely retroverted uterus and large niche with intrauterine fluid accumulation in niche and uterine cavity; (image after laparoscopic niche resection. Thickness of the residual myometrium increased and the position of the uterus changed from retroverted (A) to anteverted (B).
Studies that evaluated the effect of various surgical interventions have limited sample size and are all single armed without a comparator.18 22 25 26 Recently, we reported a large prospective cohort study, in which promising fertility and obstetric outcomes were observed in 133 women with a wish to conceive and who underwent laparoscopic resections of large and symptomatic uterine niches. Among these women 88 (66.2%) had infertility of whom 58 (43.6%) had previous failed ART and 45 (33.8%) had an active wish to conceive but without proven infertility yet. The majority of women (62%) conceived following laparoscopic niche resection with a median interval of 3 months after contraception withdrawal (Vissers et al 2023, submitted). Despite the promising results, it is too early to implement laparoscopic niche resection in daily practice as a means to improve reproductive outcomes. According to the principles of the IDEAL (Idea, Development, Exploration, Assessment and Long-term study) framework, a randomised controlled trial (RCT) the next step after optimising outcomes and studying the effect of a new technique in previous cohort studies.30 31
In the current study, we aim to compare the effect of a laparoscopic uterine niche resection with expectant management, for time to ongoing pregnancy and other reproductive outcomes in women with large niches in combination with (1) unexplained infertility for at least 1 year or (2) failed IVF or (3) problems during fertility therapy, such as intrauterine accumulation of fluid and/or technical problems to insert a catheter.
Materials and analysis
Design
The LAPRES study is a single-centre non-blinded RCT, performed in a tertiary referral centre in Amsterdam, the Netherlands, with a total follow-up of 2 years.
Participants and eligibility criteria
Women are eligible if a large uterine niche (defined as niche with a depth of >50% of the myometrial thickness and a residual myometrial thickness (RMT) ≤3 mm) is observed and if they have at least one of the following problems: (1) unexplained infertility for at least 1 year, (2) failed IVF or (3) problems during fertility therapy, such as intrauterine accumulation of fluid and/or technical problems to insert an intrauterine or embryo transfer catheter. Unexplained infertility was defined as: at least 12 months unprotected intercourse or self-insemination without contraception, regular ovulatory cycle at least one-sided tubal patency (established according to local protocol) and no male factor. Exclusion criteria are pregnancy, age <18 years, insufficient understanding of the Dutch or English language, contraindications for general anaesthesia, a (suspected) malignancy, uterine or cervical polyps, submucosal fibroids, atypical endometrial cells, cervical dysplasia, cervical or pelvic infection or an hydrosalpinx.
Recruitment and randomisation
Before study entry, the uterus and the uterine niche will be evaluated by means of transvaginal sonography. We will use a standardised protocol for the sonographic uterine and niche evaluation.7 Additionally, a pap smear will be taken if indicated or when not recently performed to exclude cervical dysplasia.
Eligible patients will be informed by one of the gynaecologists about the aims, methods, design, benefits and possible disadvantages of the laparoscopic niche resection, as a basis for informed consent (online supplemental appendix A). The informed consent form must be signed before involvement in any study-related activity. After written informed consent has been obtained, eligible women will be randomly assigned to the laparoscopic niche resection group or the expectant management group for at least 9 months. Randomisation will be blinded and managed using the research survey web-based application, which assigns a computer-generated random number to each participant. We will use a permuted block design. All women that decline to participate will be registered anonymously in order to record the number and reason for refusal. Subjects will be able to leave the study at any time and for any reason without any consequences. If women decline to participate, they are offered usual care, which does not include a laparoscopic niche resection.
Intervention (laparoscopic niche resection)
The patients assigned to the laparoscopic niche resection group will undergo a procedure under general anaesthesia in lithotomy position. Full details of the surgical procedure were published previously in our paper on short-term outcomes32 and in a step-by-step tutorial.33 In short: the laparoscopic niche resection is continuously guided by hysteroscopy. Adhesions between the uterus and bladder or between the uterus and the abdominal wall will be lysed and the bladder will be dissected from the anterior wall of the uterus and cervix. Due to the thin myometrium overlying the niche, the niche can be transilluminated with the hysteroscopic light to be visualised laparoscopically. The thin part of the niche and all fibrotic tissue will be resected. The uterotomy will be closed using at least four full-thickness single sutures (1.0 multifilament) with sliding knots that include the entire uterine wall and the endometrium. One double inverted matrass suture will be placed across the closed wound to strengthen the wound and ease the tension on the first layer of sutures. If the uterus is (extremely) retroverted even after uterine repair, the round ligaments will additionally be shortened (Baldi anterior) using two continuous running sutures (2.0 multifilament) (see figure 2). An adhesion barrier (Hyalobarrier, Nordic Pharma) will be applied after uterine closure. The anatomical result of niche closure will be evaluated by hysteroscopy at the end of the procedure. To illustrate the procedure, we included a video.33 Women were advised to use contraception in the first 6 months following niche resection to allow uterine healing prior to subsequent pregnancy.
Enlarge this image.Figure 2. Double layer full thickness closuring of the uterus with single sliding knots. (A) First layer of sliding knots. (B) Second layer of knots and suspension of the round ligaments (Baldi anterior).
Control group
The control group will receive usual care according to the local protocol of the referring centre’ for at least 9 months which means no additional surgical intervention during this period. However, patients are allowed to become pregnant and to receive fertility therapies if indicated, this includes IUI or IVF dependent on their previous received fertility therapies at inclusion. In the intervention group, patients are also allowed to receive fertility therapies if indicated after the intervention from 6 months onwards. All additional therapies received, both by intervention group members and by control group members, will be registered. Any member of the control group who has not become pregnant after 9 months will be given the opportunity to undergo a laparoscopic niche resection.
Evaluation
Patients who are referred to our tertiary referral centre because of a niche and/or related symptoms will be evaluated at our outpatient clinic by trained niche experts as a part of the standard care provision. All such patients will receive a standardised TVUS evaluation of the pelvis, ovaries and uterus. Uterine pathology will be evaluated according to the MUSA guidelines34 35 double endometrial thickness, position of the uterus and presence of sliding sign between bladder and bowels will be documented. In case of suspected adhesions, we will measure the total length of the non-sliding area between the uterus and bladder. The presence of deep endometriosis will also be evaluated.
Niches will be evaluated at baseline in all groups and at 3 months after surgery, in accordance with the international expert recommendations on the evaluation and reporting of niches.7 36 The position of the uterus (anteversion, straight, retroversion or extreme retroversion (broken uterus) and presence of a niche (defined as an indentation of at least 2 mm) and fluid accumulation in the niche or uterine cavity will be documented. Gel will be introduced if intrauterine fluid is not present in line with the recommendations of international experts.7 The length, depth, width and volume of the niche, RMT and adjacent myometrium thickness (AMT), branches of the niche visible in the sagittal and/or transversal plane and distance between the niche and the vesicovaginal fold will be measured. In addition, the presence of any large niches (RMT<50% of AMT, RMT<3 mm) will be documented. All sonographic examiners will undertake the online tutorial (www.nichelearning.online).36 This learning module is be based on the results of a Delphi procedure involving an international group of niche experts.7
Study procedures
The study will be performed in accordance with Good Clinical Practice (GCP) guidelines. Evaluation of eligibility, niche evaluation and counselling will be performed by physicians with extensive experience in those activities. The surgical interventions will be performed in our centre by at least one of the two experienced gynaecologists (JH and WJKH), each of whom has previously performed more than a hundred laparoscopic niche resections.
Patient and public involvement
In 2017, two focus group discussions (N=8 and 5) were conducted. Participants were Dutch patients with a large niche, who were scheduled for surgical treatment for their symptoms. Abnormal uterine bleeding, subfertility, sexual functioning, abdominal pain and self-esteem were themes prioritised by participants, and therefore, taken into account in our study protocol and also outcome parameters were based on input of these focus group discussions.37
Outcome measures
Primary outcome measure
The primary outcome measure is time to ongoing pregnancy, defined as a viable intrauterine pregnancy at twelve weeks gestation.
Secondary outcome measures
The key secondary outcome is time to pregnancy leading to a live birth.
Other secondary outcome measures are
Fertility and pregnancy outcomes: live birth, pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, ectopic pregnancy, pregnancy outcomes including gestational age at delivery, percentage of patients with term delivery, mode of delivery, adverse events during pregnancy and delivery.
Received fertility therapies after randomisation
Menstruation characteristics: cycle length, number of days during menstruation, postmenstrual spotting (yes or no) and number of spotting days, pain during menstruation (Verbal Rating Score: VRS), abdominal pain on non-menstruating days (VRS), urinary symptoms (shortlist of SFFI), quality of life based on Short-Form-36 (Aaronson et al, 1998),38 EQ-5D-5L (The EuroQol Group (1990)39 ; ‘EuroQol—a new facility for the measurement of health-related quality of life’, 1990) and patients self-reported satisfaction (Likert scale)
Perioperative outcomes (intervention group): surgery time, blood loss during surgery, perioperative and postoperative complications (Clavien-Dindo classification),40 hysteroscopic result immediately after laparoscopic niche resection, extent of adhesions, subjective characteristics such as surgeon satisfaction and difficulty of the procedure.
Additional interventions: applied medical and/or surgical interventions because of gynaecological symptoms will be assessed at 6 and 12 months and 2 years follow-up.
TVUS evaluation will be performed 3 months after a laparoscopic niche resection: presence of a niche, length, depth and with of the niche, RMT, AMT, accumulation of intrauterine fluid, presence of sliding sign or suspected adhesions between the bladder and uterus will be reported in the same way as at baseline.
Data collection and management
Collection of baseline characteristics and patient-reported outcomes
Baseline characteristics will be collected by means of a digital questionnaire including SF-36 domain scores, EuroQol scores and FSFI scores sent to participants’ email addresses. At 6, 12 and 24 months follow-up, further digital questionnaires will be sent to participants to assess the primary and secondary outcomes (figure 3, flow chart). Reminders for all questionnaires will be sent every 2 weeks; up to three reminders will be sent in each instance. If a participant does not respond to the reminders, a research nurse will call the participant. The gynaecologist, the research nurse or the researcher will also fill out a baseline eCRF (electronic case report form).
Intraoperative data
Immediately after the niche resection, the surgeon will be asked to register relevant items regarding the procedure in an eCRF. These items include: surgery time, blood loss during surgery, major and minor perioperative complications, hysteroscopic result immediately after laparoscopic niche resection, extent of adhesions and distance, subjective characteristics such as surgeon satisfaction and difficulty of the procedure.
Niche evaluation
All patients in the intervention group will undergo TVUS 3 months after the laparoscopic niche resection to register all uterine and niche features.
Serious adverse events
All serious adverse events (SAEs) will be reported to the medical ethics committee (MEC) by line listing yearly. Life-threatening SAEs or an event that leads to death will be reported to the MEC immediately. All SAEs will be followed until they have abated, until a stable situation has been reached or the patient was discharged.
Confidentiality and data security
All participating researchers receive a login name and password to gain access to researchservey.nl, a web-secured randomisation database. Randomisation is performed pseudoanonymously with only the initials and year of birth of the participants. Linking personal data to the study number can only be performed by the trial coordinator. Written informed consent forms are stored in a lockable room. All forms and data will be archived for 15 years in the participating centres.
Statistical analysis
Data will be analysed in accordance with the intention-to-treat principle with a sensitivity analysis according to the per-protocol principle. Baseline characteristics will be presented using percentages, means with SD and 95% CI or medians with IQRs, as appropriate. We will calculate RRs and 95% CIs for all pregnancy outcomes. To study time to ongoing pregnancy, we will construct Kaplan-Meier curves and use the log rank test to compare the treatment groups. In addition, we will estimate the marginal HR with 95% CI using a Cox proportional hazards model. The difference between the two groups in terms of all continuous variables will be analysed using the Mann-Whitney U test for non-parametric data (total number of postmenstrual spotting days during one menstrual cycle, days of spotting at the end of the menstruation, days of intermenstrual spotting, dysmenorrhoea, experienced discomfort due to spotting, niche depth and RMT). Quality of life measures over time will be analysed using linear mixed models using random intercepts for individual women and time point. Fisher’s exact test will be used for the rare binary data, such as the presence of (midcycle) intrauterine fluid and the presence of pain during micturition. Satisfaction with the randomised treatment will be recoded into a binary outcome using ‘dissatisfied’ (combining dissatisfied, very dissatisfied and neutral) or ‘satisfied’ (combining satisfied and very satisfied) and will be analysed using the χ2 test.
Predefined subgroup analyses
We aim to investigate effect modification of the intervention by the prognosis of individual women, as this avoids looking at many different characteristics separately.41 To conduct this, we first will develop a prognostic model on the data regressing pregnancy on the following list of a priori selected predictors in a Cox model: (1) age, (2) one versus more previous caesarean sections, (3) postmenstrual spotting complaints (yes or no), (4) presence of midcycle intrauterine fluid accumulation, (5) suspected presence of concomitant adenomyosis and/or endometriosis, (6) duration of infertility, (7) infertile before last CS and (8) previous failed IUI or IVF. Next, we will use the model to estimate the individual probability of pregnancy after 1 year (which represents their characteristics summarised in a prognosis ‘score’). Finally, we will fit a new Cox model regressing pregnancy on treatment allocation, score and the interaction between the two.
For the second sensitivity analysis, we will opt for the ‘cloning’ methodological approach for a treatment that is started later in time: the principle is that if the treatment decision is made at some point after diagnosis, we are comparing ‘strategies’ to eventually treat or not rather than assigning treatment at a fixed time point as in an RCT. We start with using the data from all patients for both strategies, then will follow women over time and censored, that is, remove them from analysis when they do not adhere to their assigned strategy, which here involves receiving treatment in the expectant management ‘strategy’ group. For example, a woman who received laparoscopic niche resection at 9 months after randomisation provided data on expectant management for both strategy groups during the first 9 months, was followed after laparoscopic niche resection in the treatment strategy group but censored at the time of laparoscopic niche resection in the expectant management group. Finally, we will fit adjusted (weighted) Kaplan-Meier curves for both groups and conduct a log-rank test to compare the curves. What we obtain is the absolute chance of a live birth over time for both strategies.
Additional analyses
We plan an additional analysis of effect on the primary outcome, where we exclude women who have decided for other reasons that they do not want to become pregnant for at least a year or who had another surgical intervention including but not limited to a hysteroscopic niche resection or a laparoscopic niche resection or hysterectomy (in other centres) during the first 9 months in the expectant management group. Interim analysis will not be performed because of the long-term follow-up. Total follow-up will extend to 2 years after randomisation.
Sample size calculation
When designing this study, there were no data available on the ongoing pregnancy rates in women with a large niche. However, we did have ongoing pregnancy rates in women undergoing their first IVF cycle who had one previous CS, this was 20.1% in our centre.12 We assumed that ongoing pregnancy rates will even be lower in women with a large niche.
In order to justify a new invasive surgical procedure, we defined that it should at least result in a doubling of the ongoing pregnancies rate. As such, we powered our study on the assumption that the ongoing PR increased from 20% to 40%. Assuming 40% pregnancies in the intervention group, 20% pregnancies in the control group, a (two sided) significance level of 0.05 and a power of 0.80, we need 82 women in each group. Because we expect a drop-out rate of 15%, we intend to include 200 patients
Ethics and dissemination
The study protocol has been approved by the medical ethics committee (MEC) of the Amsterdam University Medical Centre. (Ref. No. 2017.030). Protocol amendments will be communicated after approval by the central MEC of Amsterdam UMC. The trial has been registered in the International Clinical Trial Registry Platform (ICTRP) (Ref. No. NTR6534; https://trialsearch.who.int/). Eligible women will be counselled in accordance with the GCP guidelines for doctors certified according to the Basic Course on Regulations and Organisation for Clinical Researchers (BROK). Participants will sign a written informed consent before participation (online supplemental appendix A). All recommended items on the SPIRIT 2013 checklist have been addressed in this clinical trial protocol (online supplemental appendix B). The results will be communicated after final inclusion and follow-up, by means of publication in a peer-reviewed international journal and at an international conference.
Patient enrolment began in 2017. We expected completion of follow-up in 2025.
Discussion
In recent years, several innovative surgical therapies have been developed to treat niche-related symptoms or to improve reproductive outcomes. Previous smaller cohort studies reported positive effects on symptoms and reproductive outcomes after laparoscopic niche resection.18 22–24 32 However, given the lack of RCTs comparing the intervention with expectant management, we do not know exactly how the beneficial effect of laparoscopic niche resection compares with expectant management. The effect of laparoscopic niche resection on reproductive outcomes should be evaluated in RCTs before it is implemented in guidelines and daily practice. We hypothesise that laparoscopic niche resection will lead to better reproductive outcomes compared with expectant management in patients with a large niche and unexplained infertility or failed IVF.
Strengths and limitations
To our knowledge, this is the first RCT that evaluates the effect of laparoscopic niche resection in comparison to expectant management on reproductive outcomes in infertile women with a large uterine niche. The study was designed after the execution of a large cohort study in our centre where we optimised the procedure and completed our learning curve. (Vissers et al 2023, submitted). This is in line with the proposed IDEAL framework for introduction and evaluation of new surgical techniques.30 Additionally, this risk on selection bias is limited due to the fact that a laparoscopic niche resection in the Netherlands is currently not offered as a part of usual care. To reduce the chance of bias, randomisation will involve allocation concealment by means of a web-based randomisation programme. Given the nature of the procedure, the study cannot be blinded for the patient, which may possibly affect the outcomes reported by the patient.
We expect the study to have some limitations as well. We will not be able to study the safety (maternal and/or neonatal outcome) of vaginal delivery after a laparoscopic niche resection, because we advise the included patients as a part of our protocol to undergo an elective caesarean section at term. However, this advice can be debated. Although the thickness of the residual myometrium after a caesarean section and its change during the subsequent pregnancy is associated with the likelihood of a successful labour it is not clear what the optimal cut-off value is for a save and successful trial of labour.42 In addition, the chance of uterine rupture during labour is associated with a smaller RMT.43–45 There is no evidence that, even with a thick residual myometrium after laparoscopic niche resection, it is safe to deliver vaginally.
Potential impact and implications
So far, given the absence of comparative studies, there is no clear evidence that proves the additional value of a laparoscopic niche resection in order to improve fertility or pregnancy outcomes. However, an increasing number of physicians offer this innovative therapy to their patients with a niche, which may potentially lead to overtreatment. The proposed study is therefore intended to provide more conclusive evidence on the additional value of a laparoscopic niche resection compared with expectant management in women with a large niche and unexplained infertility or failed IVF. It will provide insight in effect on reproductive outcomes, in potential side effects or complications and on its effect on required fertility therapies and quality of life. These results will guide professionals on the need for uptake of this intervention in guidelines and can be used for counselling of patients with a large niche and infertility on the effect and risks of a laparoscopic niche resection.
Ethics statements
Patient consent for publication
Not applicable.
Contributors JV, SJMKM, RAdL, RvE, FAG, BWM, WJKH and JAFH contributed to the design of this study. JAFH or WJKH will perform the laparoscopic niche resections. All the authors critically revised this manuscript and approve with this version to be published.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
1 Betrán AP, Ye J, Moller A-B, et al. The Increasing Trend in Caesarean Section Rates: Global, Regional and National Estimates: 1990-2014. PLoS One 2016; 11: e0148343. doi:10.1371/journal.pone.0148343
2 Bij de Vaate AJM, Brölmann HAM, van der Voet LF, et al. Ultrasound evaluation of the cesarean scar: Relation between a niche and Postmenstrual spotting. Ultrasound Obstet Gynecol 2011; 37: 93–9. doi:10.1002/uog.8864
3 Osser OV, Jokubkiene L, Valentin L. High prevalence of defects in cesarean section scars at Transvaginal ultrasound examination. Ultrasound Obstet Gynecol 2009; 34: 90–7. doi:10.1002/uog.6395
4 Osser OV, Jokubkiene L, Valentin L. Cesarean section scar defects: Agreement between Transvaginal Sonographic findings with and without saline contrast Enhancement. Ultrasound Obstet Gynecol 2010; 35: 75–83. doi:10.1002/uog.7496
5 Vervoort AJMW, Uittenbogaard LB, Hehenkamp WJK, et al. Why do niches develop in Caesarean uterine scars? hypotheses on the Aetiology of niche development. Hum Reprod 2015; 30: 2695–702. doi:10.1093/humrep/dev240
6 Vikhareva Osser O, Valentin L. Clinical importance of appearance of cesarean Hysterotomy scar at Transvaginal Ultrasonography in Nonpregnant women. Obstet Gynecol 2011; 117: 525–32. doi:10.1097/AOG.0b013e318209abf0
7 Jordans IPM, de Leeuw RA, Stegwee SI, et al. Sonographic examination of uterine niche in non-pregnant women: A modified Delphi procedure. Ultrasound Obstet Gynecol 2019; 53: 107–15. doi:10.1002/uog.19049
8 Bij de Vaate AJM, van der Voet LF, Naji O, et al. Prevalence, potential risk factors for development and symptoms related to the presence of uterine niches following cesarean section: Systematic review. Ultrasound Obstet Gynecol 2014; 43: 372–82. doi:10.1002/uog.13199
9 van der Voet LF, Bij de Vaate AM, Veersema S, et al. Long-term complications of Caesarean section. The niche in the scar: A prospective cohort study on niche prevalence and its relation to abnormal uterine bleeding. BJOG 2014; 121: 236–44. doi:10.1111/1471-0528.12542
10 Murji A, Sanders AP, Monteiro I, et al. Cesarean scar defects and abnormal uterine bleeding: A systematic review and meta-analysis. Fertil Steril 2022; 118: 758–66. doi:10.1016/j.fertnstert.2022.06.031
11 Riemma G, De Franciscis P, Torella M, et al. Reproductive and pregnancy outcomes following embryo transfer in women with previous cesarean section: A systematic review and meta-analysis. Acta Obstet Gynecol Scand 2021; 100: 1949–60. doi:10.1111/aogs.14239
12 Vissers J, Sluckin TC, van Driel-Delprat CCR, et al. Reduced pregnancy and live birth rates after in vitro fertilization in women with previous Caesarean section: A retrospective cohort study. Hum Reprod 2020; 35: 595–604. doi:10.1093/humrep/dez295
13 Wang L, Yao W, Tang X, et al. Fertility outcomes of IVF/ICSI after Caesarean section: A cohort study. Reprod Biomed Online 2020; 40: 719–28. doi:10.1016/j.rbmo.2019.12.004
14 Wang L, Wang J, Lu N, et al. Outcomes of patients with prior cesarean section after a single embryo transfer in IVF/ICSI: A retrospective cohort study. Front Endocrinol (Lausanne) 2022; 13. doi:10.3389/fendo.2022.851213
15 Gurol-Urganci I, Bou-Antoun S, Lim CP, et al. Impact of Caesarean section on subsequent fertility: A systematic review and meta-analysis. Hum Reprod 2013; 28: 1943–52. doi:10.1093/humrep/det130
16 Fabres C, Arriagada P, Fernández C, et al. Surgical treatment and follow-up of women with Intermenstrual bleeding due to cesarean section scar defect. J Minim Invasive Gynecol 2005; 12: 25–8. doi:10.1016/j.jmig.2004.12.023
17 Vissers J, Hehenkamp W, Lambalk CB, et al. Post-Caesarean section niche-related impaired fertility: Hypothetical mechanisms. Hum Reprod 2020; 35: 1484–94. doi:10.1093/humrep/deaa094
18 Donnez O. Cesarean scar defects: Management of an iatrogenic pathology whose prevalence has dramatically increased. Fertil Steril 2020; 113: 704–16. doi:10.1016/j.fertnstert.2020.01.037
19 Donnez O, Jadoul P, Squifflet J, et al. Laparoscopic repair of wide and deep uterine scar Dehiscence after cesarean section. Fertil Steril 2008; 89: 974–80. doi:10.1016/j.fertnstert.2007.04.024
20 Erickson SS, Van Voorhis BJ. Intermenstrual bleeding secondary to cesarean scar Diverticuli: Report of three cases. Obstet Gynecol 1999; 93 (5 Pt 2): 802–5. doi:10.1016/s0029-7844(98)00314-7
21 Gubbini G, Centini G, Nascetti D, et al. Surgical Hysteroscopic treatment of cesarean-induced Isthmocele in restoring fertility: Prospective study. J Minim Invasive Gynecol 2011; 18: 234–7. doi:10.1016/j.jmig.2010.10.011
22 Harjee R, Khinda J, Bedaiwy MA. Reproductive outcomes following surgical management for Isthmoceles: A systematic review. J Minim Invasive Gynecol 2021; 28: 1291–302. doi:10.1016/j.jmig.2021.03.012
23 He Y, Zhong J, Zhou W, et al. Four surgical strategies for the treatment of cesarean scar defect: A systematic review and network meta-analysis. J Minim Invasive Gynecol 2020; 27: 593–602. doi:10.1016/j.jmig.2019.03.027
24 van der Voet LF, Vervoort AJ, Veersema S, et al. Minimally invasive therapy for gynaecological symptoms related to a niche in the Caesarean scar: A systematic review. BJOG 2014; 121: 145–56. doi:10.1111/1471-0528.12537
25 Verberkt C, Klein Meuleman SJM, Ket JCF, et al. Fertility and pregnancy outcomes after a uterine niche resection in women with and without infertility: A systematic review and meta-analysis. F&S Reviews 2022; 3: 174–89. doi:10.1016/j.xfnr.2022.05.003
26 Vitale SG, Ludwin A, Vilos GA, et al. From Hysteroscopy to Laparoendoscopic surgery: What is the best surgical approach for symptomatic Isthmocele? A systematic review and meta-analysis. Arch Gynecol Obstet 2020; 301: 33–52. doi:10.1007/s00404-020-05438-0
27 Tahara M, Shimizu T, Shimoura H. Preliminary report of treatment with oral contraceptive pills for Intermenstrual vaginal bleeding secondary to a cesarean section scar. Fertil Steril 2006; 86: 477–9. doi:10.1016/j.fertnstert.2006.01.020
28 Jacobson MT, Osias J, Velasco A, et al. Laparoscopic repair of a Uteroperitoneal Fistula. JSLS 2003; 7: 367–9.
29 Vervoort A, van der Voet LF, Hehenkamp W, et al. Hysteroscopic resection of a uterine Caesarean scar defect (niche) in women with Postmenstrual spotting: A randomised controlled trial. BJOG 2018; 125: 326–34. doi:10.1111/1471-0528.14733
30 McCulloch P, Cook JA, Altman DG, et al. IDEAL framework for surgical innovation 1: The idea and development stages. BMJ 2013; 346. doi:10.1136/bmj.f3012
31 Nikkels C, Vervoort A, Mol BW, et al. IDEAL framework in surgical innovation applied on Laparoscopic niche repair. Eur J Obstet Gynecol Reprod Biol 2017; 215: 247–53. doi:10.1016/j.ejogrb.2017.06.027
32 Vervoort A, Vissers J, Hehenkamp W, et al. The effect of Laparoscopic resection of large niches in the uterine Caesarean scar on symptoms, ultrasound findings and quality of life: A prospective cohort study. BJOG 2018; 125: 317–25. doi:10.1111/1471-0528.14822
33 Huirne JAF, Vervoort A, Leeuw RD, et al. Technical aspects of the Laparoscopic niche resection, a step-by-step Tutorial. Eur J Obstet Gynecol Reprod Biol 2017; 219: 106–12. doi:10.1016/j.ejogrb.2017.09.019
34 Van den Bosch T, de Bruijn AM, de Leeuw RA, et al. Sonographic classification and reporting system for diagnosing adenomyosis. Ultrasound Obstet Gynecol 2019; 53: 576–82. doi:10.1002/uog.19096
35 Harmsen MJ, Van den Bosch T, de Leeuw RA, et al. Consensus on revised definitions of morphological uterus Sonographic assessment (MUSA) features of adenomyosis: Results of modified Delphi procedure. Ultrasound Obstet Gynecol 2022; 60: 118–31. doi:10.1002/uog.24786
36 Verberkt C, Jordans IPM, Van den Bosch T, et al. How to perform standardized Sonographic examination of uterine niche in non-pregnant women. Ultrasound Obstet Gynecol 2022; 60: 420–4. doi:10.1002/uog.24953
37 Stegwee SI, Beij A, de Leeuw RA, et al. Niche-related outcomes after Caesarean section and quality of life: A focus group study and review of literature. Qual Life Res 2020; 29: 1013–25. doi:10.1007/s11136-019-02376-6
38 Aaronson NK, Muller M, Cohen PD, et al. Translation, validation, and Norming of the Dutch language version of the SF-36 health survey in community and chronic disease populations. J Clin Epidemiol 1998; 51: 1055–68. doi:10.1016/s0895-4356(98)00097-3
39 EuroQol Group. Euroqol-a new facility for the measurement of health-related Qualityof life. Health Policy 1990; 16: 199–208. doi:10.1016/0168-8510(90)90421-9
40 Dindo D, Demartines N, Clavien P-A. Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205–13. doi:10.1097/01.sla.0000133083.54934.ae
41 Kent DM, Steyerberg E, van Klaveren D. Personalized evidence based medicine: Predictive approaches to heterogeneous treatment effects. BMJ 2018; 363. doi:10.1136/bmj.k4245
42 Naji O, Wynants L, Smith A, et al. Predicting successful vaginal birth after cesarean section using a model based on cesarean scar features examined by Transvaginal Sonography. Ultrasound Obstet Gynecol 2013; 41: 672–8. doi:10.1002/uog.12423
43 Naji O, Daemen A, Smith A, et al. Changes in cesarean section scar dimensions during pregnancy: A prospective longitudinal study. Ultrasound Obstet Gynecol 2013; 41: 556–62. doi:10.1002/uog.12334
44 Bujold E, Jastrow N, Simoneau J, et al. Prediction of complete uterine rupture by Sonographic evaluation of the lower uterine segment. Am J Obstet Gynecol 2009; 201: 320. doi:10.1016/j.ajog.2009.06.014
45 Pomorski M, Fuchs T, Zimmer M. Prediction of uterine Dehiscence using ultrasonographic parameters of cesarean section scar in the Nonpregnant uterus: A prospective observational study. BMC Pregnancy Childbirth 2014; 14. doi:10.1186/s12884-014-0365-3
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; Saskia J M Klein Meuleman 2 ; de Leeuw, Robert A 2 ; Rik van Eekelen 3 ; Groenman, Freek A 2 ; Mol, Ben W 4
; Hehenkamp, Wouter J K 2 ; Huirne, Judith A F 2 1 Department of Gynaecology and Obstetrics, Amsterdam, The Netherlands; Department of Gynaecology and Obstetrics, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
2 Department of Gynaecology and Obstetrics, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
3 Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, The Netherlands
4 OB/GYN, School of Medicine, Monash University, Melbourne, Victoria, Australia