Effectiveness of laparoscopic niche resection versus expectant management in patients with unexplained infertility and a large uterine caesarean scar defect (uterine niche): protocol for a randomised controlled trial (the LAPRES study).

INTRODUCTION: A uterine niche is a defect at the site of the uterine caesarean scar that is associated with gynaecological symptoms and infertility. Promising results are reported in cohort studies after a laparoscopic niche resection concerning reduction of gynaecological symptoms in relation to baseline and concerning pregnancy outcomes. However, randomised controlled trials to study the effect of a laparoscopic niche resection on reproductive outcomes in infertile women are lacking. This study will answer the question if laparoscopic niche resection in comparison to expectant management improves reproductive outcomes in infertile women with a large uterine niche. METHODS AND ANALYSIS: The LAPRES study is a randomised, non-blinded, controlled trial, including 200 infertile women with a total follow-up of 2 years. Women with the presence of a large niche in the uterine caesarean scar and unexplained infertility of at least 1 year or failed IVF will be randomly allocated to a laparoscopic niche resection within 6 weeks or to expectant management for at least 9 months. A large niche is defined as a niche with a depth of >50% of the myometrial thickness and a residual myometrium of ≤3 mm on transvaginal ultrasound. Those receiving expectant management will be allowed to receive fertility therapies, including assisted reproductive techniques, if indicated. The primary outcome is time to ongoing pregnancy, defined as a viable intrauterine pregnancy at 12 weeks' gestation. Secondary outcome measures are time to conception leading to a live birth, other pregnancy outcomes, received fertility therapies after randomisation, menstruation characteristics, patient satisfaction, quality of life, additional interventions, and surgical and ultrasound outcomes (intervention group). Questionnaires will be filled out at baseline, 6, 12 and 24 months after randomisation. Ultrasound evaluation will be performed at baseline and at 3 months after surgery. ETHICS AND DISSEMINATION: The study protocol was approved by the medical ethics committee of the Amsterdam University Medical Centre. (Ref. No. 2017.030). Participants will sign a written informed consent before participation. The results of this study will be submitted to a peer-reviewed journal for publication. TRIAL REGISTRATION NUMBER DUTCH TRIAL REGISTER REF NO NL6350 : http://www.trialregister.nl.

Definition and Criteria for Diagnosing Cesarean Scar Disorder.

Importance: Approximately 60% of women develop a uterine niche after a cesarean delivery (CD). A niche is associated with various gynecological symptoms including abnormal uterine bleeding, pain, and infertility, but there is little consensus in the literature on the distinction between the sonographic finding of a niche and the constellation of associated symptoms. Objective: To achieve consensus on defining the clinical condition that constitutes a symptomatic uterine niche and agree upon diagnostic criteria and uniform nomenclature for this condition. Design, Setting, and Participants: A consensus based modified electronic Delphi (eDelphi) study, with a predefined Rate of Agreement (RoA) of 70% or higher. Experts were selected according to their expertise with niche-related consultations, publications, and participation in expert groups and received online questionnaires between November 2021 and May 2022. Main Outcomes and Measures: Definition, nomenclature, symptoms, conditions to exclude, and diagnostic criteria of an illness caused by a symptomatic uterine niche. Results: In total, 31 of the 60 invited experts (51.7%) participated, of whom the majority worked in university-affiliated hospitals (28 of 31 [90.3%]), specialized in benign gynecology (20 of 31 [64.5%]), and worked in Europe (24 of 31 [77.4%]). Three rounds were required to achieve consensus on all items. All participants underlined the relevance of a new term for a condition caused by a symptomatic niche and its differentiation from a sonographic finding only. Experts agreed to name this condition cesarean scar disorder, defined as a uterine niche in combination with at least 1 primary or 2 secondary symptoms (RoA, 77.8%). Defined primary symptoms were postmenstrual spotting, pain during uterine bleeding, technical issues with catheter insertion during embryo transfer, and secondary unexplained infertility combined with intrauterine fluid. Secondary symptoms were dyspareunia, abnormal vaginal discharge, chronic pelvic pain, avoiding sexual intercourse, odor associated with abnormal blood loss, secondary unexplained infertility, secondary infertility despite assisted reproductive technology, negative self-image, and discomfort during participation in leisure activities. Consensus was also achieved on certain criteria that should be met and conditions that should be excluded before making the diagnosis. Conclusions and Relevance: In this modified Delphi study, a panel of 31 international niche experts reached consensus for the constellation of symptoms secondary to a uterine niche and named it cesarean scar disorder.