Single or Double-layer Uterine Closure Techniques
Condition: Uterine Scar; Cesarean Section Complications; Cesarean Section; Dehiscence
Study type: Interventional

Summary: 
      There are different surgical techniques of uterine closure during cesarean. A growing data
      has suggested that the closure technique has an effect on uterine scar healing. Residual
      myometrium thickness and uterine scar defect (niche) development seems to be related to the
      single or double layer closure of uterus. In that study, investigators will search for the
      effect of single or double layer closure of uterus during cesarean on the uterine scar
      defect.
    

Detailed description: 
      Study design and participants This study will be assessed cesarean delivery (CD) patients who
      will admit to the Obstetrics and Gynecology Clinic of the Başkent University Adana Dr. Turgut
      Noyan Research and Application Center between July 2018 and September 2019. Specifically,
      participants will be singleton pregnancy patients between 18-45 years of age who will be in
      gestational weeks 24-41 and had not previously received any uterine operations such as CS or
      myomectomy. Patients with multiple pregnancies and/or chronic inflammatory diseases such as
      systemic lupus erythematosus, rheumatoid arthritis, and insulin-dependent diabetes mellitus
      will be excluded. All patients who meet the inclusion criteria will be randomized into two
      treatment groups (i.e., single- or double-layer closures).

      This study was approved by Başkent University Institutional Review Board and Ethics Committee
      (Project no= KA18-71, Approval Date= 7/27/2018), and supported by Başkent University Research
      Fund. Patients who will agree to participate in the study will be informed about the purpose
      of the study before their operations, and each provided signed written consent.

      Participants will be also assessed for maternal age, gravidity, parity, body mass index,
      smoking status, diabetes mellitus, hypertensive diseases of pregnancy, and medical history.
      Regardless of whether they had contractions before surgery, this study also will be
      determined patient CD indications, levels of cervical dilatation, and how CD will be
      established (i.e., elective or emergent).

      Randomization and masking A table of random numbers is used as a simple randomization method
      for placing participants into the two treatment groups. The Research Randomizer website
      (https://www.randomizer.org/) was used to create this table. Before the intervention, the
      next envelope among a previously prepared, sealed, and the number-ordered stack will be
      opened by a nurse for each procedure.

      Surgery technique Six operators will perform CD operations. Access to the abdomen will be
      achieved via Pfannenstiel incision, while the Kerr incision technique will be applied to the
      uterus for all patients. Patients in the single-layer group will be received uterus closures
      with locking, while patients in the double-layer group will be received uterus closures with
      locking in the first layer, but without locking and using the Lambert style in the second
      layer. The decidua will be deliberately excluded during all suturations. A synthetic
      absorbable suture material (Vicryl 1.0, Ethicon, Somerville, NJ, USA) will be used during all
      uterus closures, with corner stitches that will be applied to all patients. Additional suture
      usages and numbers will be reported only in cases of bleeding. Both uterine closure and whole
      operation times will be recorded by the respective operating room technicians. Finally,
      intravenous prophylactic antibiotics (2 g cefazolin sodium) and uterotonic medications (10 IU
      oxytocin) will be routinely applied during all CD procedures.

      Follow-up Postoperative follow-ups will be completed in March 2020. All participants will be
      called after delivery and will be invited to complete sixth-month evaluations. However,
      participants who will experience post-CD pregnancies or uterine surgeries will be excluded.
      All remaining participants will be examined at six to nine months period after CD for niche
      presence in the scar region, niche measurements, scar shape, distance between niche and the
      external cervical os and residual myometrium thickness (RMT), and adjacent myometrium
      thicknesses (AMT). The distance between the niche and external os should be measured parallel
      to the top of the main niche, from the most distal niche point to external os. These
      examinations will be conducted by two experienced sonographers who will be blinded to
      clinical information regarding the closure technique. Procedures will be specifically
      completed using a 4-10 MHz transducer (E8C-RS micro convex endocavity probe, Voluson S6, GE,
      Milwaukee, US), ultrasonography, and through the saline infusion sonohysterography (SIS)
      method. The cervix will be first cleaned with povidone iodine while the patient will be on
      the gynecological examination table prior to ultrasonography. The SIS process then will be
      progressed toward the inside of the endometrial cavity by passing from the cervical os with
      an intrauterine insemination cannula (intrauterine insemination catheter, Wallace Artificial
      Insemination Catheter, Smiths Medical International Ltd., Ashford, Kent, UK). A sterile
      saline solution will be applied to sufficiently distend the cavity, while ultrasonography
      will be conducted via transvaginal probe. At this time, the presence of a hypoechogenic area
      with a depth of 2mm or deeper in the CD scar region within the endometrial cavity will be
      accepted as a niche. Niche dimensions will be determined via 3-axis measurements for depth,
      length, and width. Niche shape, distance to the external cervical os, RMT, and AMT will be
      evaluated. During these follow-ups, patients will be also asked about their menstruation
      processes and any experiences of cervical pain, menstruation pain, postmenstrual bleeding
      (PMB) in the form of spotting, and other abnormal bleeding patterns. Those who will
      experience bleeding for two days or more in the form of spotting after menstruation will be
      defined as PMB. Participants who will use intrauterine devices after CD and/or those who
      could not tolerate speculum application will be examined via transvaginal ultrasonography (TV
      USG).

      Outcomes Primary outcomes will be considered niche presence and measurements, while secondary
      outcomes will be considered RMT, AMT, healing ratio, postmenstrual spotting, and
      dysmenorrhea.

      Statistical analyses The sample size was calculated based on a study by Di Spiezio Sardo et
      al. (2017) titled Risk of Cesarean Scar Defect Following Single- vs Double-Layer Uterine
      Closure: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Their study
      revealed niche formation rates for single- and double-layer closure types of 25% and 43%,
      respectively. Based on tools available at the Power and Sample Size website
      (http://powerandsamplesize.com/Calculators), the needed sample size was calculated at 141 for
      each treatment group with 90% power and 0.05 alpha error.

      All data were statistically analyzed using the IBM SPSS 21.0 software. Categorical
      measurements will be presented as frequencies and percentages, while continuous measurements
      will be summarized as means and standard deviations (median and range when needed).
      Distributions will be checked and the student's t-test was will be used for variables meeting
      the parametric test assumptions when comparing the continuous measurements based on groups,
      while the Mann Whitney U test will be used for those that will not meet the parametric test
      assumptions. Finally, chi-square or Fisher's test statistics will be used to compare
      categorical variables. Statistical significance is set to 0.05 for all tests.
    

Intervention name(s): Residual myometrium thickness; Niche Presence; Adjacent myometrium thickness; Niche Measurements (depth of niche, width of niche, length of niche)
Intervention type(s): Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test
Intervention description(s): The myometrium will be closed by single or double layer during cesarean and residual myometrium thickness will be evaluated in 6 to 9 months by saline infusion sonography.; The myometrium will be closed by single or double layer during cesarean and niche presence will be evaluated in 6 to 9 months by saline infusion sonography.; The myometrium will be closed by single or double layer during cesarean and adjacent myometrium thickness will be evaluated in 6 to 9 months by saline infusion sonography.; The myometrium will be closed by single or double layer during cesarean and three dimensional niche measurements will be evaluated in 6 to 9 months by saline infusion sonography.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective Randomised Trial
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: cesarean section, niche, isthmocele, uterine closure