Reproductive outcomes after laparoscopic resection of symptomatic niches in uterine cesarean scars: Long-term follow-up on the prospective LAPNICHE study.

INTRODUCTION: After incomplete healing of the uterine cesarean section scar, a niche can be observed; 24% of the women develop large niches with a residual myometrial thickness <3 mm. In these cases a laparoscopic resection is possible. The effect of this new treatment on fertility outcome is not known yet. This paper describes reproductive outcomes 2 years after a laparoscopic niche resection and compares women with or without secondary infertility at baseline. MATERIAL AND METHODS: A prospective cohort study was performed, with consecutive inclusion of women between 2011 and 2019. Women with a niche in the uterine cesarean scar, with a residual myometrial thickness of <3 mm and with a desire to become pregnant, were scheduled to undergo a laparoscopic niche resection because of one or more of the following problems (1) postmenstrual spotting; (2) midcycle intrauterine fluid accumulation diagnosed during the fertility workup or (3) difficulties with a previous embryo transfer and preferring a surgical therapy. The study is registered in the ISRCTN register (ref. no. ISRCTN02271575) on April 23, 2013. RESULTS: There were 133 (62%) women included with a desire to become pregnant, 88 with secondary infertility. In all, 83 had an ongoing pregnancy at the 2-year follow-up. The ongoing pregnancy rate in patients with previous fertility problems was 60.2% compared with 66.7% in patients without infertility (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.32-1.7). The OR for live births was 0.57 (95% CI 0.02-1.2). Overall, 8.3% of the pregnancies resulted in miscarriages by the 2-year follow-up. CONCLUSIONS: The reproductive outcomes in women with and without previous fertility problems undergoing resection of a large niche are very promising and quite comparable in both groups. These results suggest, but do not prove, a beneficial effect of this therapy for these indications. The results support the design of future randomized controlled trials to evaluate the effect of niche resection vs expectant management to assess its additional value in women with or without fertility problems who desire pregnancy.

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.

Increased amplitude of subendometrial contractions identified by ultrasound speckle tracking in women with a caesarean scar defect.

RESEARCH QUESTION: What is the effect of a caesarean scar defect on subendometrial contractions? DESIGN: Prospective cohort study in a Dutch medical centre including women with a niche in the uterine caesarean section scar. Data were compared with controls without a caesarean section scar. All women underwent a 5-min recording by transvaginal ultrasound at four phases in the menstrual cycle: during menses; late follicular; early luteal; or late luteal phase. Uterine motion analysis was evaluated by dedicated speckle tracking using two-dimensional optical flow. MAIN OUTCOME: amplitude of the subendometrial contractions. RESULTS: Thirty-one women with a niche in the uterine scar and 11 controls, matched for menstrual cycle phase, were included. The amplitude of the subendometrial contractions was significantly higher in women with a niche compared with controls during all phases of the menstrual cycle (menses P < 0.001; late follicular P < 0.001; early luteal P = 0.028; late luteal P = 0.003). Velocity was lower in women with a niche during late follicular phase only (P = 0.012). A positive correlation between niche sizes (depth, length) and amplitude of subendometrial contractions was found. CONCLUSION: Subendometrial contractions were affected in women with a niche in the caesarean section scar compared with women who had not undergone a previous caesarean section. Contraction amplitude was higher and independent of the menstrual phase. These findings may cause postmenstrual spotting, dysmenorrhoea and lower implantation rates in women with a niche. Future studies should investigate this association and the underlying pathways.

Change of the residual myometrial thickness during pregnancy in women who underwent laparoscopic niche resection compared with controls without niche surgery: a prospective comparative cohort study.

BACKGROUND: Reduced residual myometrial thickness before and during pregnancy is associated with uterine rupture or dehiscence after vaginal birth after cesarean delivery. Laparoscopic niche resection performed in case of gynecologic symptoms has shown to increase residual myometrial thickness 6 months after surgery. OBJECTIVE: This study aimed to evaluate the change in residual myometrial thickness from baseline value before pregnancy to the third trimester of pregnancy in women with and without laparoscopic niche resection and evaluate niche presence, niche size during pregnancy vs before pregnancy, and obstetrical outcomes, including uterine rupture and dehiscence in both study groups. STUDY DESIGN: This was a prospective cohort study conducted in an academic medical center. Of note, 2 groups of pregnant women with a previously diagnosed niche were included: (1) women with a large symptomatic niche (residual myometrial thickness of <3 mm) followed by laparoscopic niche resection (LNR group) and (2) women with a niche without niche resection because of minimal symptoms or a residual myometrial thickness of ≥3 mm diagnosed before current pregnancy (expectant group). Participants underwent a transvaginal ultrasound at 12, 20, and 30 weeks of gestation. Changes in residual myometrial thickness and changes in niche measurements over time were analyzed with linear mixed models. RESULTS: A total of 100 women were included, 61 in the LNR group and 39 in the expectant group. The change in residual myometrial thickness from baseline value before niche resection to the third trimester of pregnancy was +2.0 mm in the LNR group vs -1.6 mm in the expectant group (P<.001). Residual myometrial thickness decreased from the first trimester of pregnancy onward in both groups. Although residual myometrial thickness was thinner at baseline in the LNR group, it was thicker in the LNR group than in the expectant group during all trimesters: 3.2 mm (P<.001) in the first trimester of pregnancy, 2.5 mm (P<.001) in the second trimester of pregnancy, and 1.8 mm (P=.001) in the third trimester of pregnancy. Uterine dehiscence was reported in 1 of 50 women (2%) in the LNR group and 7 of 36 women (19%) in the expectant group (P=.007) and was related to the depth of niche-to-residual myometrial thickness ratio before pregnancy (after niche resection) and residual myometrial thickness in the second trimester of pregnancy. No uterine rupture was reported. Most patients received a scheduled cesarean delivery in both groups. There was more blood loss during subsequent cesarean delivery in the LNR group than in the expectant group. CONCLUSION: Here, laparoscopic niche resection resulted in an increased residual myometrial thickness during a subsequent pregnancy. Moreover, a lower number of dehiscence was found in the LNR group than in the expectant group without niche surgery. Per-section blood loss was higher in the LNR group than in the expectant group. In general, laparoscopic niche resection is performed to improve gynecologic symptoms. Currently, there is no evidence to support a laparoscopic niche resection to improve obstetrical outcomes, but the trend toward more uterine dehiscence encourages further research.

Post-Caesarean section niche-related impaired fertility: hypothetical mechanisms.

Caesarean section can result in an indentation of the myometrium at the site of the Caesarean scar, called a niche. Niches can cause symptoms of abnormal uterine blood loss, dysmenorrhoea, chronic pelvic pain and dyspareunia and are possibly related to subfertility. Various other explanations for the cause of subfertility after Caesarean section have been proposed in the literature, such as uterine pathology, intra-abdominal adhesions and women's reproductive choices. Not all niches cause symptoms and the relation with subfertility and a niche in the uterine scar still needs further study since direct evidence is lacking so far. Based on the limited available evidence, and in combination with observations made during sonographic hysteroscopic evaluations and laparoscopic niche repair, we propose and discuss three hypothetical mechanisms: (i) the environment for sperm penetration and implantation may be detrimental; (ii) there could be a physical barrier to embryo transfer and implantation; and (iii) psychogenic factors may reduce the likelihood of pregnancy. Several innovative surgical treatments have been developed and are being implemented for niche-related problems. Promising results are reported, but more evidence is needed before further implementation in daily practice. The additional value of niche resections should be compared to expectant management or fertility therapies, such as ART, in randomized controlled trials. Therefore, our suggested hypotheses should, for the time being, not be used for justification of any specific procedures outside clinical trials.