Single or Double-layer Uterine Closure Techniques Following Cesarean: An Ongoing Debate
Phase: NA
Conditions: Uterine Scar, Cesarean Section Complications, Cesarean Section; Dehiscence
Sponsor: Safak Baran Yilmaz

 
Official title: Single or double-layer uterine closure techniques following cesarean: an ongoing debate  
Document date: 07/27/2018 
Clinical trial number: NCT03629028 
 
 
 
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 erythematous, 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 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 number-
ordered stack will be opened by a nurse for each procedure.  
Surgery technique 
Six operators will perform the 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 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  

 
Official title: Single or double-layer uterine closure techniques following cesarean: an ongoing debate  
Document date: 07/27/2018 
Clinical trial number: NCT03629028 
 
 
 
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), 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-squared or Fisher’s test statistics will be used to 
compare categorical variables. Statistical significance is set to 0.05 for all tests. 
 
 
 
 
 

 
Official title: Single or double-layer uterine closure techniques following cesarean: an ongoing debate  
Document date: 07/27/2018 
Clinical trial number: NCT03629028 
 
 
 
 
 
 
BAŞKENT UNIVERSITY CLINICAL RESEARCHES ETHICS COMMITTEE  
INFORMED CONSENT FORM FOR SCIENTIFIC RESEARCH 
 
 
 
1. TITLE OF PROJECT: Single or double-layer uterine closure techniques following cesarean: an 
ongoing debate  
2. VOLUNTEER NUMBER: The total number of volunteers envisaged to include the research is 
282 
3. DURATION: The period foreseen to take part in this research is 6-9 months. 
4. PURPOSE OF THE RESEARCH: The aim of this study is to investigate the effect of single or 
double- layered closure of the uterine area opened during cesarean section on the formation 
of space in the uterine incision site in long term. 
5. TERMS OF PARTICIPATION IN THE RESEARCH:  
a) Between the ages of 18 and 45  
b) Singleton pregnancies 
c) Women who had not previously undergone any uterine operations such as cesarean 
delivery or myomectomy
PLEASE READ CAREFULLY!!! 
You have been invited to participate in a clinical trial for scientific research. Before accepting to 
take part in this study, you need to understand the purpose of the study and make your decision 
freely after being informed about the research. This information form has been prepared specifically 
for you in order to introduce this research in detail. If there are points about the research that you 
have not understood even though it is stated in this form, ask your doctor and ask for clear answers 
to your questions. You are free to join this research or not. Participation in the study is voluntarily. 
Once you are informed about the research, your physician will give you time before signing the form 
so that you can freely make your decision. Regardless of your decision, your physicians will perform 
their duties to ensure and maintain your full health from now on. If you agree to participate in the 
research, sign the form. 

Official title: Single or double-layer uterine closure techniques following cesarean: an ongoing debate  
Document date: 07/27/2018 
Clinical trial number: NCT03629028 
 
 
6. GENERAL INFORMATION ABOUT PROCEDURE  
Recent studies in the literature report that, no clear difference has been found between 
single or double layer uterine closure during cesarean delivery. In this study, we aim to 
establish a clear consensus about the uterine closure and contribute to the literature. For 
this reason, during the cesarean operation, one of the two techniques, which are valid for 
the uterine closure, will be performed to you. The operation time may vary depending on 
the person until bleeding control is achieved. We will call you and invite to follow-up in 6 
to 9 months after the cesarean delivery. In your follow-up we will ask your complaints 
and we will perform transvaginal ultrasonography to evaluate your cesarean scar region. 
7. RESPONSIBILITIES OF THE VOLUNTEER 
a. You should follow the research plan and the researcher's recommendations. 
b. You should come to follow-up on the dates specified by the researcher. 
c.  You should inform your doctor if you become pregnant following your cesarean operation. 
d. You should report any medical conditions that bother you during the investigation to your doctor 
(investigator).8.BENEFITS 
The surgical procedure, which will be performed, may not provide any additional benefit to you as a 
result of this research. Our research is for scientific purposes only and is not expected to benefit you 
directly or change the course of your treatment. However, the results obtained from this research 
will contribute to the planning of the other patients who are diagnosed like you or to provide benefit
to your subsequent births. 
9. RISKS 
This study does not consist an additional risk apart from the risks mentioned in the routine cesarean
delivery informed consent form. 
10. RESPONSIBILITY TO THE PARTICIPICANT 
In case of any complication due to cesarean procedure, Başkent University will take the 
responsibility for your treatment. 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
Official title: Single or double-layer uterine closure techniques following cesarean: an ongoing debate  
Document date: 07/27/2018 
Clinical trial number: NCT03629028 
 
 
11. NAME OF PRINCIPAL INVESTIGATOR 
Hi, I’m Dr Şafak Yılmaz Baran, I’m the principal investigator of this study. If you have any questions, 
you may ask me now or later, even after the cesarean operation. You may contact with me. (Hospital 
phone: 03224586868/22109, personal phone: 05055830856, Address: Baskent University Adana 
Application and Research Center, Adana, Turkey) 
12. REIMBURSEMENTS 
Your participation is free. You will not be given any other money or gifts to take part in this research
13. NAME OF ORGANIZATION 
This study is supported and funded by Başkent University.  
14.CONFIDENTIALITY 
Medical information about your operation and postoperative conditions during the research will be
recorded with a unique code number and all reports will be kept confidential. The results of the
research will be used for scientific purposes only. Even if the research is published, your credentials
will not be given. However, if necessary, the investigators of the research, ethical committees and
officials will be able to access your medical information. You can access your own medica
information whenever you want. 
15.EXCLUSION CRITERIA 
In case of not attending the follow-up after cesarean operation in 6-9 months, or getting pregnant in
the postoperative period, we will exclude you from the study. This situation will not cause any
changes in your treatment and surgical procedures. However, even if you are excluded from the
research, medical data about you can be used for scientific purposes.  
16.RIGHT TO REFUSE OR WITHDRAW 
Joining to this research is entirely up to you. You can refuse to join the research or leave 
the research at any stage. If you refuse to take part in the research or give up after 
participating, your decision will not cause any change in the treatment applied to you. 
Medical data related to you may be used for scientific purposes even if you withdraw or 
be removed by the researcher. 
17.SHARING THE RESULTS 
While the research is in progress, new medical information and results related to the 
research will be sent to you or your legal representative as soon as possible. These results 
may affect your desire to continue research. In this case, you may want to stop the 
investigation until you decide. 

 
 
 
 
Official title: Single or double-layer uterine closure techniques following cesarean: an 
ongoing debate  
Document date: 07/27/2018 
Clinical trial number: NCT03629028 
 
 
 
I have read the foregoing information, or it has been read to me. I have had the 
opportunity to ask questions about it and any questions that I have asked have 
been answered to my satisfaction. I consent voluntarily to participate as a 
participant in this research. 
 
 
 
 
 
 
 
INVESTIGATOR 
SIGNATURE 
NAME OF THE 
INVESTIGATOR
 
 
 
ADDRESS 
 
TELEPHONE 
 
DATE 
 
PARTICIPICANT 
SIGNATURE 
NAME 
 
ADDRESS 
TELEPHONE 
DATE