Single-layer vs double-layer uterine closure during cesarean delivery: 3-year follow-up of a randomized controlled trial (2Close study).

BACKGROUND: The rising rate of cesarean deliveries has led to an increased incidence of long long-term complications, including niche formation in the uterine scar. Niche development is associated with various gynecologic complaints and complications in subsequent pregnancies, such as uterine rupture and placenta accreta spectrum disorders. Although uterine closure technique is considered a potential risk factor for niche development, consensus on the optimal technique remains elusive. OBJECTIVE: We aimed to evaluate the effect of single-layer vs double-layer closure of the uterine incision on live birth rate at a 3-year follow-up with secondary objectives focusing on gynecologic, fertility, and obstetrical outcomes at the same follow-up. STUDY DESIGN: A multicenter, double-blind, randomized controlled trial was performed at 32 hospitals in the Netherlands. Women ≥18 years old undergoing a first cesarean delivery were randomly assigned (1:1) to receive either single-layer or double-layer closure of the uterine incision. The primary outcome of the long-term follow-up was the live birth rate; with secondary outcomes, including pregnancy rate, the need for fertility treatment, mode of delivery, and obstetrical and gynecologic complications. This trial is registered on the International Clinical Trials Registry Platform www.who.int (NTR5480; trial finished). RESULTS: Between 2016 and 2018, the 2Close study randomly assigned 2292 women, with 830 of 1144 and 818 of 1148 responding to the 3-year questionnaire in the single-layer and double-layer closure. No differences were observed in live birth rates; also there were no differences in pregnancy rate, need for fertility treatments, mode of delivery, or uterine ruptures in subsequent pregnancies. High rates of gynecologic symptoms, including spotting (30%-32%), dysmenorrhea (47%-49%), and sexual dysfunction (Female Sexual Function Index score, 23) are reported in both groups. CONCLUSION: The study did not demonstrate the superiority of double-layer closure over single-layer closure in terms of reproductive outcomes after a first cesarean delivery. This challenges the current recommendation favoring double-layer closure, and we propose that surgeons can choose their preferred technique. Furthermore, the high risk of gynecologic symptoms after a cesarean delivery should be discussed with patients.

Niche-related outcomes after caesarean section and quality of life: a focus group study and review of literature.

BACKGROUND: A niche in the uterus, present in 60% of women after caesarean section (CS), is associated with several gynaecological symptoms and possibly with subfertility. Studies that focus on quality of life (QoL) in relation to a niche are lacking. PURPOSE: To identify niche-related outcomes that influence QoL and to compare patient-reported outcomes with outcomes studied in the literature. METHODS: Two focus group discussions (FGDs, N = 8 and 5) were conducted in Amsterdam UMC-location VUmc. Participants were Dutch patients with a large niche, with (planned) surgical treatment for their symptoms. Niche-related symptoms and impact on functioning or participation were fixed topics. The transcripts of the FGDs were coded into outcomes, themes and domains of QoL according to the WHOQOL model. Additionally, participants created a top five important outcomes. Next, we performed a systematic review (SR) on niche-related outcomes and compared the FGDs with niche-related outcomes from the SR. RESULTS: In four domains (physical health, psychological domain, social relationships and environment), fifteen themes were reported in the FGDs. Abnormal uterine bleeding (AUB), subfertility, sexual activity, abdominal pain and self-esteem were themes prioritised by participants. In the literature, gynaecological symptoms and reproductive outcomes were predominantly studied. Sexuality and self-esteem were prioritised in the FGDs but hardly or never studied in the literature. CONCLUSION: We found a broad range of niche-related outcomes influencing QoL. Apart from symptoms evaluated in the literature such as AUB, abdominal pain and subfertility, clinicians and researchers should be more aware of sexual activity and self-esteem in this population.

Prognostic model on niche development after a first caesarean section: development and internal validation.

OBJECTIVE: To develop and internally validate a prognostic prediction model for development of a niche in the uterine scar after a first caesarean section (CS). STUDY DESIGN: Secondary analyses on data of a randomized controlled trial, performed in 32 hospitals in the Netherlands among women undergoing a first caesarean section. We used multivariable backward logistic regression. Missing data were handled using multiple imputation. Model performance was assessed by calibration and discrimination. Internal validation using bootstrapping techniques took place. The outcome was 'development of a niche in the uterus', defined as an indentation of ≥ 2 mm in the myometrium. RESULTS: We developed two models to predict niche development: in the total population and after elective CS. Patient related risk factors were: gestational age, twin pregnancy and smoking, and surgery related risk factors were double-layer closure and less surgical experience. Multiparity and Vicryl suture material were protective factors. The prediction model in women undergoing elective CS revealed similar results. After internal validation, Nagelkerke R2 ranged from 0.01 to 0.05 and was considered low; median area under the curve (AUC) ranged from 0.56 to 0.62, indicating failed to poor discriminative ability. CONCLUSIONS: The model cannot be used to accurately predict the development of a niche after a first CS. However, several factors seem to influence scar healing which indicates possibilities for future prevention such as surgical experience and suture material. The search for additional risk factors that play a role in development of a niche should be continued to improve the discriminative ability.

Cost-effectiveness of single-layer versus double-layer uterine closure during caesarean section on postmenstrual spotting: economic evaluation alongside a randomised controlled trial.

OBJECTIVE: To evaluate the cost-effectiveness of double-layer compared with single-layer uterine closure after a first caesarean section (CS) from a societal and healthcare perspective. DESIGN: Economic evaluation alongside a multicentre, double-blind, randomised controlled trial. SETTING: 32 hospitals in the Netherlands, 2016-2018. PARTICIPANTS: 2292 women ≥18 years undergoing a first CS were randomly assigned (1:1). Exclusion criteria were: inability for counselling, previous uterine surgery, known menstrual disorder, placenta increta or percreta, pregnant with three or more fetuses. 1144 women were assigned to single-layer and 1148 to double-layer closure. We included 1620 women with a menstrual cycle in the main analysis. INTERVENTIONS: Single-layer unlocked uterine closure and double-layer unlocked uterine closure with the second layer imbricating the first. MAIN OUTCOME MEASURES: Spotting days, quality-adjusted life-years (QALYs), and societal costs at 9 months of follow-up. Missing data were imputed using multiple imputation. RESULTS: No significant differences were found between single-layer versus double-layer closure in mean spotting days (1.44 and 1.39 days; mean difference (md) -0.056, 95% CI -0.374 to 0.263), QALYs (0.663 and 0.658; md -0.005, 95% CI -0.015 to 0.005), total healthcare costs (€744 and €727; md €-17, 95% CI -273 to 143), and total societal costs (€5689 and €5927; md €238, 95% CI -624 to 1108). The probability of the intervention being cost-effective at willingness-to-pay of €0, €10 000 and €20 000/QALY gained was 0.30, 0.27 and 0.25, respectively, (societal perspective), and 0.55, 0.41 and 0.32, respectively, (healthcare perspective). CONCLUSION: Double-layer uterine closure is not cost-effective compared with single-layer uterine closure from both perspectives. If this is confirmed by our long-term reproductive follow-up, we suggest to adjust uterine closure technique guidelines. TRIAL REGISTRATION NUMBER: NTR5480/NL5380.

Improved health-related quality of life in the first year after laparoscopic niche resection: a prospective cohort study.

OBJECTIVE: To evaluate changes in health-related quality of life (HRQOL) the first year after laparoscopic niche resection. STUDY DESIGN: Prospective cohort study in women with a large niche (residual myometrium thickness <3.0 mm) after caesarean section who underwent laparoscopic niche resection between May 2010 and January 2018. Women were included consecutively. 36-Item Short Form Survey (SF-36) was sent at baseline, three and twelve months postoperatively. All participants that filled out the questionnaire at baseline were included. Physical (PCS) and mental component summary scores (MCS) and scores for subdomains were calculated. Scores were analysed over time using Wilcoxon signed rank test. RESULTS: 146 participants responded to the SF-36 at baseline, of which 129 (88.4 %) responded at three or twelve months follow-up. After three months, median PCS and MCS improved, compared to baseline (p = 0.014 and p = 0.008, respectively). Subdomains physical functioning, bodily pain, general health, vitality, mental health and social functioning improved significantly. At twelve months follow-up, improvement in PCS and MCS did not reach statistical significance (p = 0.053 and p = 0.063, respectively). Subdomains bodily pain (77.6-89.8, p < 0.001), mental health (76-80, p = 0.004) and social functioning (75-87.5, p = 0.016) improved significantly. Women with symptom relief as main goal of the intervention showed larger improvement in PCS than women with distorted anatomy and to restore anatomy as main goal for the intervention (p = 0.001). CONCLUSION: Laparoscopic niche resection improves HRQOL in women with a large niche in physical and mental domains three and twelve months postoperatively.