Single-Layer Versus Double-Layer Uterine Closure After Primary Cesarean Section
Single-Layer Versus Double-Layer Uterine Closure After Primary Cesarean Section: Impact on Residual Myometrial Thickness and Cesarean Scar Defect Formation - A Prospective Randomized Controlled Trial
This study compares two surgical techniques for closing the uterus after cesarean section: single-layer versus double-layer closure. The primary objective is to determine which technique results in better uterine scar healing, measured by residual myometrial thickness (RMT) and cesarean scar defect (niche) prevalence at 6 weeks and 6 months postoperatively.
BACKGROUND:
Cesarean section is one of the most common surgeries worldwide. After fetal delivery, the uterine incision must be closed by suture. Poor scar healing can lead to niche formation, abnormal bleeding, pelvic pain, dyspareunia, and complications in future pregnancies including uterine rupture and placenta accreta.
INTERVENTION:
Participants are randomized 1:1 to receive either:
- Single-layer closure: one continuous non-locking suture through full myometrial thickness
- Double-layer closure: two successive extra-mucosal non-locking sutures excluding the decidua
ASSESSMENTS:
Transvaginal ultrasound at 6 weeks and 6 months measures RMT and niche presence. Standardized symptom questionnaires assess pelvic pain, spotting, dysmenorrhea, and dyspareunia.
ELIGIBILITY:
Women aged 18-45 years undergoing primary cesarean section with singleton pregnancy at term (gestational age ≥ 37 weeks).
ENROLLMENT: 384 participants (192 per group)
SETTING: Department of Obstetrics and Gynecology, Hedi Chaker University Hospital, Sfax, Tunisia
FOLLOW-UP: 6 months per participant in which the patients attend 2 follow-up visits:
First visit 6 weeks after surgery. Second visit at 6 months after surgery
.And have a pelvic ultrasound at each visit
Visão geral do estudo
Status
Condições
Descrição detalhada
BACKGROUND AND RATIONALE
Cesarean section is one of the most commonly performed surgical procedures worldwide. After fetal delivery, the uterine incision must be closed by suture using one of two accepted techniques: single-layer or double-layer closure. Despite widespread use of both methods : no consensus exists regarding which technique produces superior long-term uterine scar healing.
Poor scar healing can result in a niche. formation (isthmocele), defined as a triangular anechoic indentation of the anterior uterine wall at the scar site with depth greater than or equal to 2 mm (Jordan et al., 2019). Niches occur in 25-70% of women after cesarean section and are associated with postmenstrual spotting, chronic pelvic pain, dyspareunia, fertility impairment, and serious obstetric complications in future pregnancies, including placenta accreta spectrum and uterine rupture.
The residual myometrial thickness (RMT) is the primary ultrasound marker of scar healing quality, defined as the minimum myometrial thickness at the scar site. An RMT below 2.5 mm is associated with a substantially increased risk of uterine rupture in subsequent pregnancies.
Previous studies comparing single-layer and double-layer closure have been limited by heterogeneous populations including scarred uteri, non-standardized surgical techniques, inconsistent ultrasound protocols, and insufficient sample sizes. No study has focused exclusively on primary cesarean sections with a fully standardized operative protocol.
SURGICAL TECHNIQUES
Single-Layer Closure (Group A): The uterine incision is closed with one continuous non-locking suture incorporating the full thickness of the myometrium in one pass, including the decidua.
Double-Layer Closure (Group B): The uterine incision is closed with two successive non-locking extra-mucosal sutures, excluding the decidua. Layer 1 approximates the inner half of the myometrium. Layer 2 buries the first layer, incorporating the outer half of the myometrium and uterine serosa.
All other operative steps are strictly standardized across both groups.
ULTRASOUND ASSESSMENT PROTOCOL
Transvaginal ultrasound (TVUS) is performed by blinded trained sonographers using Samsung HS40 with EVN4-9 probe (4-9 MHz), with empty bladder, preferably in the follicular phase (Day 7-14 of the menstrual cycle), in the mid-sagittal plane.
RMT is measured perpendicular to the serosa at the thinnest scar point. Adjacent myometrial thickness (AMT) is measured 5-10 mm from the scar on both sides. The myometrial ratio is calculated as RM (%) = RMT/AMT x 100.
Niche dimensions (depth, length, width) and volume (ellipsoid formula) are recorded when present.
RANDOMIZATION
Participants are randomized 1:1 using the Clinical Trial Randomization Tool with permuted blocks of variable sizes (4, 6, and 8). Allocation is revealed to the operating surgeon immediately before hysterorrhaphy, after fetal and placentaldelivery. Participants and ultrasound assessors are blinded to group allocation.
STATISTICAL ANALYSIS
Primary analysis uses multiple linear regression for RMT and binary logistic regression for niche prevalence, adjusted for age, BMI, gestational age, uterine exteriorization, surgeon category, and cesarean indication.
Advanced analyses include linear mixed-effects models for repeated measures, Firth penalized logistic regression for predictive modeling, counterfactual mediation analysis (Imai et al.) with bootstrap validation (10,000 replications), inverse probability weighting for loss to follow-up, and five-scenario multiple imputation (MICE).
Software: SPSS v26.0 and R v4.3. Reporting: CONSORT 2010 guidelines.
ETHICAL CONSIDERATIONS
This trial is conducted in accordance with the Declaration of Helsinki (2013), ICH-GCP E6(R2), and Tunisian national regulations. Ethical approval was obtained from the Ethics Committee of the Faculty of Medicine of Sfax (Approval No. 31/26). All participants provide written informed consent. Participation is voluntary and withdrawal is permitted at any time without consequence to medical care.
Tipo de estudo
Inscrição (Real)
Estágio
- Não aplicável
Contactos e Locais
Locais de estudo
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Sfax Governorate
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Sfax, Sfax Governorate, Tunísia, 3000
- Hedi Chaker university hospital
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
- Women aged 18 years or older
- Singleton pregnancy
- Gestational age ≥ 37 weeks (term pregnancy)
- Scheduled or emergency primary cesarean section (first cesarean delivery, no previous uterine scar)
- Low transverse uterine incision (Pfannenstiel or Joel-Cohen approach)
- Ability to provide written informed consent
- Willingness to attend follow-up visits at 6 weeks and 6 months postoperatively
- Patient affiliated to a social security system or equivalent healthcare coverage
Exclusion Criteria:
- Previous uterine surgery (prior cesarean section, myomectomy, uterine perforation, or any procedure leaving a uterine scar)
- Multiple pregnancy (twins or higher-order multiples)
- Preterm delivery (gestational age < 37 weeks)
- Classical (vertical) or inverted T uterine incision
- Placenta previa or placenta accreta spectrum disorder
- Active uterine infection or chorioamnionitis at time of surgery
- Coagulation disorders or anticoagulant therapy
- Immunosuppressive therapy or conditions affecting wound healing (systemic corticosteroids, immunosuppressants)
- Severe maternal comorbidities (uncontrolled diabetes, connective tissue disorders, chronic renal failure)
- Participation in another interventional clinical trial
- Patient unable to attend scheduled follow-up visits
- Patient unable to understand or sign informed consent
- Fetal demise or major fetal malformation
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Outro
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Comparador Ativo: Single-layer Uterine Closure (HPU)
Participants allocated to this arm undergo primary cesarean section with single-layer uterine closure (hysterorrhaphy).
After fetal and placental extraction, the uterine incision is closed in one single layer using a continuous absorbable suture (polyglactin 910 or equivalent), which approximates the myometrium in a running unlocked pattern.
No second imbricating layer is performed.
Additional interrupted sutures (reinforcement stitches) may be placed if necessary for bleeding control.
All participants are followed postoperatively with standardized transvaginal ultrasound assessments at 6 weeks and 6 months to evaluate residual myometrial thickness (RMT) and cesarean scar defect (niche) development, as well as clinical symptom monitoring.
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After fetal and placental delivery, the uterine incision is closed in one single layer using a continuous absorbable suture (polyglactin 910) approximating the full myometrial thickness in a running pattern.
No second reinforcement layer is performed.
Additional reinforcement sutures are placed if needed.
This represents the conventional standard technique for uterine closure at cesarean section.
Outros nomes:
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Experimental: Double-layer Uterine Closure (HDP)
articipants allocated to this arm undergo primary cesarean section with double-layer uterine closure (hysterorrhaphy).
After fetal and placental extraction, the uterine incision is closed in two distinct layers using a continuous absorbable suture (polyglactin 910 or equivalent).
The first layer approximates the myometrium with a running unlocked suture.
The second layer invaginates the first using a continuous suture to reinforce the closure and improve hemostasis.
Additional interrupted sutures (reinforcement stitches) may be placed if necessary for bleeding control.
All participants are followed postoperatively with standardized transvaginal ultrasound assessments at 6 weeks and 6 months to evaluate residual myometrial thickness (RMT) and cesarean scar defect (niche) development, as well as clinical symptom monitoring.
|
After fetal and placental delivery, the uterine incision is closed in two layers using continuous absorbable suture (polyglactin 910).
Layer 1: running suture approximating the full myometrial thickness.
Layer 2: continuous imbricating suture reinforcing the first layer and improving hemostasis.
Additional reinforcement sutures placed if needed.
Aims to optimize uterine scar healing and reduce cesarean scar defect (niche) formation.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Residual Myometrial Thickness (RMT) at the Cesarean Scar at 6 Weeks and 6 Months
Prazo: 6 weeks and 6 months after cesarean section
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Residual myometrial thickness (RMT) measured in millimeters at the thinnest point of the uterine scar using standardized transvaginal two-dimensional ultrasound, performed by blinded sonographers according to the protocol of Naji et al. (2012).
RMT compared between single-layer (HPU) and double-layer (HDP) closure groups at 6 weeks and 6 months postoperatively.
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6 weeks and 6 months after cesarean section
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Prevalence of Cesarean Scar Defect (Niche) at 6 Weeks and 6 Months Postoperatively
Prazo: 6 weeks and 6 months after cesarean section
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Cesarean scar defect (niche) defined as a hypoechoic triangular indentation at the site of the uterine incision with depth ≥ 2mm or residual myometrial thickness (RMT)/adjacent myometrial thickness (AMT) ratio < 50%, detected by standardized transvaginal two-dimensional ultrasound.
Prevalence compared between single-layer (HPU) and double-layer (HDP) closure groups at 6 weeks and 6 months postoperatively.
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6 weeks and 6 months after cesarean section
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Prevalence of Gynecological Symptoms Related to Cesarean Scar Defect
Prazo: Day 10, 6 weeks, and 6 months after cesarean section
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Assessment of symptoms potentially related to uterine scar defect including: postmenstrual spotting, menometrorrhagia, dysmenorrhea, chronic pelvic pain, dyspareunia, urinary symptoms, and abnormal uterine bleeding at day 10 postoperatively.
Symptoms assessed by standardized clinical questionnaire at 6 weeks and 6 months.
Compared between HPU and HDP groups.
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Day 10, 6 weeks, and 6 months after cesarean section
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Identification of Independent Risk Factors for Cesarean Scar Defect Formation
Prazo: 6 weeks and 6 months after cesarean section
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Identification of independent risk factors for cesarean scar defect (niche) at 6 weeks and 6 months using multivariate logistic regression analysis.
Variables assessed include: closure technique, operative duration, use of reinforcement sutures, uterine position, BMI, parity, type of cesarean section (elective vs emergency), and cervical dilation at time of surgery.
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6 weeks and 6 months after cesarean section
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Cesarean Scar Defect Linear Dimensions
Prazo: 6 weeks and 6 months after cesarean section
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Length, width, and depth of detected cesarean scar defect measured in millimeters by transvaginal ultrasound at 6 weeks and 6 months.
Unit of Measure: Millimeters (mm)
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6 weeks and 6 months after cesarean section
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Cesarean Scar Defect Volume
Prazo: 6 weeks and 6 months post-cesarean
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Estimated volume of cesarean scar defect calculated using ellipsoid formula: V(mm³) = (π/6) × Length × Width × Depth Unit of Measure: Cubic millimeters (mm³)
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6 weeks and 6 months post-cesarean
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Operative Duration of Hysterorrhaphy and Total Cesarean Section
Prazo: preoperative (during cesarean section procedure)
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Measurement of time (minutes and seconds) required for uterine closure (hysterorrhaphy duration) and total operative time from skin incision to skin closure.
Number of suture materials used and frequency of additional reinforcement sutures also recorded.
Compared between HPU and HDP groups.
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preoperative (during cesarean section procedure)
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Intraoperative Complications Rate
Prazo: Perioperative : During cesarean section procedure
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Rate of intraoperative complications including hemorrhage requiring transfusion, bladder injury, ureteral injury, and unintended uterine incision extension.
Unit of Measure: Number of events (n) and percentage (%)
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Perioperative : During cesarean section procedure
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Postoperative Infectious Complications Rate
Prazo: Up to 6 weeks after cesarean section
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Rate of postoperative infectious complications including endometritis, surgical site infection, and urinary tract infection, assessed during hospitalization and at 6-week visit.
Unit of Measure: Number of events (n) and percentage (%)
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Up to 6 weeks after cesarean section
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Hospital Length of Stay
Prazo: Up to 5 days after cesarean section
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Number of days from cesarean section to hospital discharge.
Unit of Measure: Days
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Up to 5 days after cesarean section
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Blood Transfusion Requirement
Prazo: Up to 5 days after cesarean section
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Number of packed red blood cell units transfused during hospitalization.
Unit of Measure: Number of units
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Up to 5 days after cesarean section
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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Mediation Analysis: Role of Early Scar Defect in Late Outcome
Prazo: 6 weeks and 6 months after cesarean section
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Formal mediation analysis (Baron-Kenny approach, Sobel test, non-parametric bootstrap with 10,000 replications) to quantify the proportion of the protective effect of double-layer closure on 6-month niche prevalence that is mediated through prevention of early niche formation at 6 weeks.
Proportion of mediated effect and direct/indirect effects will be calculated.
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6 weeks and 6 months after cesarean section
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Development of a Clinical Symptom-Based Predictive Score for Cesarean Scar Defect
Prazo: 6 months after cesarean section
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Development and internal validation of a clinical predictive score based exclusively on self-reported symptoms (spotting, dysmenorrhea, pelvic pain, cycle irregularity) to identify patients at risk of cesarean scar defect at 6 months, without requiring ultrasound.
Firth penalized logistic regression, 10-fold cross-validation, and bootstrap validation will be performed.
AUC, sensitivity, specificity, PPV, NPV reported.
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6 months after cesarean section
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Identification of a Functional RMT Threshold Associated with Symptomatic Risk
Prazo: 6 weeks and 6 months after cesarean section
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Identification of a residual myometrial thickness (RMT) threshold at 6 weeks postoperatively that is associated with increased risk of gynecological symptoms at 6 months, using ROC curve analysis and dose-response gradient assessment.
This threshold will complement existing obstetric safety thresholds by adding a functional/symptomatic dimension.
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6 weeks and 6 months after cesarean section
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Derbel Mohamed, Professor, Department of obstetric and gynaecology of Hedi Chaker sfax
- Investigador principal: Khanfir Fatma, Professor, Department of obstetric and gynaecology of Hedi Chaker sfax
Publicações e links úteis
Publicações Gerais
- Bij de Vaate AJ, van der Voet LF, Naji O, Witmer M, Veersema S, Brolmann HA, Bourne T, Huirne JA. Prevalence, potential risk factors for development and symptoms related to the presence of uterine niches following Cesarean section: systematic review. Ultrasound Obstet Gynecol. 2014 Apr;43(4):372-82. doi: 10.1002/uog.13199.
- Jordans IPM, de Leeuw RA, Stegwee SI, Amso NN, Barri-Soldevila PN, van den Bosch T, Bourne T, Brolmann HAM, Donnez O, Dueholm M, Hehenkamp WJK, Jastrow N, Jurkovic D, Mashiach R, Naji O, Streuli I, Timmerman D, van der Voet LF, Huirne JAF. Sonographic examination of uterine niche in non-pregnant women: a modified Delphi procedure. Ultrasound Obstet Gynecol. 2019 Jan;53(1):107-115. doi: 10.1002/uog.19049.
- Di Spiezio Sardo A, Saccone G, McCurdy R, Bujold E, Bifulco G, Berghella V. Risk of Cesarean scar defect following single- vs double-layer uterine closure: systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2017 Nov;50(5):578-583. doi: 10.1002/uog.17401. Epub 2017 Oct 9.
- Roberge S, Demers S, Berghella V, Chaillet N, Moore L, Bujold E. Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and metaanalysis. Am J Obstet Gynecol. 2014 Nov;211(5):453-60. doi: 10.1016/j.ajog.2014.06.014. Epub 2014 Jun 6.
- Stegwee SI, Ben AJ, El Alili M, van der Voet LF, de Groot CJM, Bosmans JE, Huirne JAF; 2Close study group. Cost-effectiveness of single-layer versus double-layer uterine closure during caesarean section on postmenstrual spotting: economic evaluation alongside a randomised controlled trial. BMJ Open. 2021 Jul 2;11(7):e044340. doi: 10.1136/bmjopen-2020-044340.
Datas de registro do estudo
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Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
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Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças urogenitais
- Doenças Genitais
- Dor
- Manifestações Neurológicas
- Processos Patológicos
- Doenças Urogenitais Femininas
- Doenças urogenitais femininas e complicações na gravidez
- Doenças uterinas
- Doenças Genitais Femininas
- Hemorragia
- Hemorragia Uterina
- Condições Patológicas, Sinais e Sintomas
- Sinais e sintomas
- Dor pélvica
- Metrorragia
Outros números de identificação do estudo
- 31/26
Plano para dados de participantes individuais (IPD)
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