Cervical Cerclage for Preventing Spontaneous Preterm Birth in Twin Pregnancies With Transvaginal Ultrasound Cervical Length ≤ 15mm: a Study Protocol for a Randomized Clinical Trial
Phase: NA
Conditions: Twin Pregnancy With Antenatal Problem, Preterm Birth, Short Cervix
Sponsor: Thomas Jefferson University

 
 
Cervical cerclage for preventing spontaneous preterm birth in 
twin pregnancies with transvaginal ultrasound cervical length 
≤ 15mm: a study protocol for a randomized clinical trial 
ClinicalTrials.gov ID: NCT03340688 
 
 
 
 
 
 
 
 
 
 
 
05/22/2017 
Principal Investigator: 
Amanda Roman-Camargo, MD 
Division of Maternal-Fetal Medicine 
Department of Obstetrics and Gynecology 
Thomas Jefferson University Hospital 
833 Chestnut Street, First Floor, Philadelphia, PA 
Email: amanda.roman@jefferson.edu 
Phone: 215-955-9200 
Fax: 215-955-5041 
Initial version: April 26/2017 

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Table of Contents 
STUDY SUMMARY 
4 
1 INTRODUCTION 
4 
1.1 BACKGROUND 
5 
1.2 CLINICAL DATA TO DATE 
5 
1.3 RISK/BENEFITS 
5 
2 STUDY OBJECTIVES 
7 
2.1 PRIMARY OBJECTIVE 
7 
2.2 SECONDARY OBJECTIVE 
8 
3 STUDY DESIGN 
8 
3.1 GENERAL DESIGN 
8 
3.2 PRIMARY STUDY ENDPOINTS 
8 
3.3 SECONDARY STUDY ENDPOINTS 
8 
4 SUBJECT SELECTION AND WITHDRAWAL 
9 
4.1 INCLUSION CRITERIA 
9 
4.2 EXCLUSION CRITERIA 
9 
4.3 SUBJECT RECRUITMENT AND SCREENING 
9 
5 STUDY 
12 
5.1 DESCRIPTION 
12 
5.2 TREATMENT REGIMEN 
12 
5.3 METHOD FOR ASSIGNING SUBJECTS TO TREATMENT GROUPS 
12 
5.4 PLACEMENT OF CERCLAGE 
12 
6 STUDY PROCEDURES 
12 
6.1 CERVICAL MEASUREMENT 
12 
6.2 RANDOMIZATION 
13 
6.3 INTERIM CONTACTS 
13 
6.4 CERCLAGE REMOVAL 
13 
6.5 PREGNANCY OUTCOME 
13 
7 STATISTICAL PLAN 
13 

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7.1 SAMPLE SIZE DETERMINATION 
13 
7.2 STATISTICAL METHODS 
14 
8 SAFETY AND ADVERSE EVENTS 
14 
8.1 DEFINITIONS 
14 
8.2 RECORDING OF ADVERSE EFFECTS 
15 
8.3 REPORTING OF ADVERSE EFFECTS AND UNANTICIPATED PROBLEMS 
16 
8.3.1 Investigator reporting: Notifying the principal investigator 
16 
8.3.2 Investigator reporting: Notifying the IRB 
17 
8.4 MEDICAL MONITORING 
19 
8.4.1 Data and Safety Monitoring Board 
19 
9 DATA HANDLING AND RECORD KEEPING 
19 
9.1 CONFIDENTIALITY 
19 
9.2 SOURCE DOCUMENTS 
20 
9.3 RECORDS RETENTION 
20 
10 STUDY MONITORING, AUDITING, AND INSPECTING 
20 
10.1 STUDY MONITORING PLAN 
20 
10.2 AUDITING AND INSPECTING 
21 
11 ETHICAL CONSIDERATIONS 
21 
12 CONFLICT OF INTEREST 
21 
13 PUBLICATION PLAN 
21 
14 REFERENCES 
22 
 
 
 
 
 
 
 
 
 
 

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List of Abbreviations  
AE: Adverse Event  
CI: Confidence Interval  
CL: Cervical Length  
HIPAA: Health Insurance Privacy and Portability Act of 1996  
IRB Institutional Review Board  
PTB: Preterm Birth  
RCT: Randomized Controlled Trial  
SAE: Serious Adverse Event  
TVU CL: Transvaginal ultrasound cervical length 
UIC: Ultrasound indicated cerclage 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Summary 
 
Title  
Cervical cerclage for preventing spontaneous 
preterm birth in twin pregnancies with 
transvaginal ultrasound cervical length ≤ 15mm: 
a study protocol for a randomized clinical trial 
Short Title  
Cerclage for Twins with short cervix  
Methodology  
Multi-center, open label, randomized trial  
Study Duration  
3 years for subject enrollment, and an additional 
6 months for analysis and manuscript 
preparation: 2017-2021 
Study Center 
Thomas Jefferson University  
Objectives  
The primary objective of this study is to 
determine if ultrasound indicated cerclage 
reduces the incidence of spontaneous preterm 
birth in asymptomatic women with twin 
gestations with transvaginal ultrasound cervical 
length ≤ 15mm before 24 weeks of gestation.  
Number of Subjects  
200 
Diagnosis and Main Inclusion Criteria  
Women, age older than 18, with a twin gestation 
and transvaginal ultrasound cervical length 
≤15mm  between 16 to 23 6/7 weeks gestation  
Study Product and Planned Use  
Cervical cerclage  
Reference therapy  
Standard obstetrical care include daily vaginal 
progesterone 400mg from diagnosis of cervical 
length ≤25mm (usually 20 weeks) to 36 weeks  
Statistical Methodology  
Statistical analysis will be based on the intention-
to-treat principle. The risk of spontaneous 
preterm birth before 34 weeks will be quantified 
by use of the odds ratio and 95% CI. Multivariate 
analysis will be performed using logistic 
regression.  
 
 
 
 
 

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1 Introduction 
This document is a protocol for a human research study. 
1.1 Background 
The incidence of preterm birth (PTB) in the United States is 9.63% with 390,000 deliveries occurring at 
less than 37 weeks gestation annually, however the incidence of early preterm (less than 34 weeks) have 
remained steady at  2.76%, with this being the most vulnerable neonatal group.1  Risk factors for 
spontaneous preterm births include a previous preterm birth, multiple pregnancies, black race, smoking, 
periodontal disease, low maternal body-mass index and short cervical length.1, 2 
In 2015, the twin birth rate was 33.5 twins per 1000 total births. The twin birth rate increased steadily 
by 76% overall from 1980 to 2009. The number of twin births has risen substantially due to the 
increased use of assisted reproductive technology. Twin pregnancies have 59% incidence of PTB before 
37 weeks and 10.7% incidence of PTB < 32 week, 10 times more at risk of low birth-weight infants (LBW) 
and had 5 times more risk of early neonatal death.1, 3  The increased rate of preterm birth in twins is 
associated with increased neonatal morbidity and mortality rates. Disorders related to short gestation 
and LBW (low birth weight) is the second cause of infant death (17.2%).1, 4  
In singleton pregnancies with risk factors for PTB, effective medical interventions have been identified to 
reduce the risk of recurrent PTB. In women with singleton pregnancy and history of  PTB, weekly 
treatment with intramuscular 17-alpha hydroxyprogesterone caproate beginning at 16-20 weeks 
gestation until 36 weeks5 and ultrasound indicated cervical cerclage for women with transvaginal 
ultrasound cervical length (TVU CL) ≤ 25mm identified before 24 weeks of gestation have shown 
effective to decrease PTB by 44% and 30% respectively.6 Women with singleton pregnancy with no 
history of PTB and incidental finding of cervical length ≤25mm before 24 weeks of gestation will benefit 
from vaginal progesterone.7 
Similar to singleton pregnancy, in twin pregnancy TVU CL ≤25mm before 24 weeks of gestation identify 
women at risk of preterm birth.8, 9 For example the calculated risk of PTB <36 week for a twin pregnancy 
with TVU CL ≤25mm at 20 weeks is 83% while TVU CL ≤15mm at the same gestational age is 94%, and 
the calculated risk of PTB < 32 weeks is 69% and 78% respectively. Several randomized clinical trials have 
evaluated the effectiveness of 17-alpha hydroxyprogesterone caproate,10 11, 12 vaginal progesterone, 
pessary or ultrasound indicated cervical cerclage13-15 in women with twin pregnancy TVU CL less than 
25mm before 24 weeks with no significant difference between study vs control group.  However, to 
date, no trial has evaluated the potential benefit of a cerclage in twins, specifically for women with a 
TVU CL ≤15mm 
1.2 Clinical Data to Date 
Pessary: 

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A recent pessary trial conducted on women with twin pregnancy and TVU CL < 30mm at three 
institutions (TJUH, University of Pennsylvania and Naples, Italy) showed no significant decrease in the 
incidence of preterm birth <34 weeks or improvement in the perinatal outcome.16 Other similar trials in 
USA and Europe have shown conflicting results. A meta-analysis evaluating all available studies 
concluded that the use of the pessary in twin pregnancies with short TVU CL at 16-24 weeks does not 
prevent SPTB or improve perinatal outcome.17 
Vaginal progesterone: 
An Egyptian randomized clinical trial of twin gestation with TVU CL 20-25 mm between 20 to 24 weeks 
of gestation using daily 400mg vaginal progesterone versus no progesterone showed a significant 33% 
and 60% decrease in preterm labor <34 week: 41/116 (35.3 %) vs 57/108 (52.8 %) RR: 0.67 (0.49–0.90) 
and preterm labor <32 week: 14/116 (12.1 %) vs 32/108 (29.6 %) RR: 0.40 (0.23–0.72) respectively and 
33% decreased in neonatal respiratory distress: 82/229 (35.8 %) vs 111/210 (52.9 %) RR: 0.67 (0.54–
0.84).18  
A recently published meta-analysis and individual patient database including 303 women (159 assigned 
to vaginal progesterone, 144 assigned to placebo/no treatment) and their 606 infants from six 
randomized controlled trials) concluded that the use of daily 400mg of vaginal progesterone in women 
with twin pregnancy and TVU CL ≤ 25 mm decreased the risk of preterm birth <34 week and <32 weeks 
by 29% and 49% respectively and decreased on composite neonatal morbidity and mortality by 47%: 
23/84 (27.3%) vs 28/70 (40%) RR: 0.57 (0.36-0.93).19 This therapy seems to be more effective in twins 
with TVU CL 20 to 25mm (n=207) and maybe useful between 10-19mm (n=84), but a significant 
decrease in preterm birth was not seen when TVU CL is <10 mm (n=14), however the sample size in 
these last two subgroups were too small to conclude.  
Based on this new information, we at the Maternal Fetal Medicine Division at TJUH considered that 
there is enough evidence to initiate routine screening for preterm birth with TVU CL in women with twin 
pregnancies from 18 to 24 weeks and to offer daily 400mg of vaginal progesterone to those women with 
TVU CL ≤ 25mm as a standard practice since February 2017.  
Cervical cerclage: 
Three randomized clinical trials with 49 twin gestations with a TVU CL ≤ 25 mm were included in an 
individual patient data meta-analysis (only 7 women had TVU CL ≤ 15 mm). Adjusting for previous 
preterm birth and gestational age at randomization, there were no statistically significant differences 
preterm birth <34 weeks (aOR 1.17, 95% CI 0.23-3.79) and neonatal outcomes. They conclude that 
cerclage cannot currently be recommended for clinical use in twin pregnancies with a maternal short 
cervical length in the second trimester and larger trials are still necessary.20 
A retrospective cohort of 140 women twin pregnancy with TVU CL ≤ 25mm before 24 weeks showed 
that cervical cerclage did not decrease the incidence of PTB < 34 weeks, however the subgroup of 
women twin pregnancy with very short TVU CL ≤ 15mm before 24 weeks (n=71) showed that cervical 

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cerclage significantly decreased the PTB < 34 weeks by 49% from 30/39 (76.9%) to 15/32 (46%) aOR: 
0.51 (0.31–0.83), with significant prolongation of pregnancy by almost 4 weeks and decreased admission 
to NICU by 59% from 63/75 neonates (84%) to 38/58 (65.5%) aOR: 0.41 (0.24–0.81). 21  
A second retrospective cohort study including 80 women with twin pregnancy and TVU CL ≤ 25mm 
before 24 weeks showed that cervical cerclage decreased the PTB < 32 weeks by 60% from 20/60 
(76.9%) to 15/32 (46%) (RR, 0.40 (95% CI, 0.20–0.80)).22 
These two studies were limited by the retrospective nature of the cohort, were originated from different 
institutions during several years of collection, and the overall management of the cases were different, 
therefore final recommendation cannot be made and a prospective randomized trial will be needed to 
corroborate these findings. 
We hypothesized that women with twin pregnancy and asymptomatic TVU CL ≤ 15mm identified before 
23 6/7 weeks receiving a combination of daily vaginal progesterone and cervical cerclage will have 
significantly decreased preterm birth < 34 weeks, and will improved perinatal morbidity and mortality 
when compared with daily vaginal progesterone alone.   
1.3 Risk/Benefits 
The major risks of ultrasound indicated cerclage that have been reported in previous studies involving 
singleton pregnancies include intraoperative rupture of membranes (less than 1%), cervical laceration, 
cervical bleeding, chorioamnionitis (undiagnosed at the time of cerclage or acquired post cerclage 
placement), failure to place the cerclage and failure of the cerclage on prolonging pregnancy with 
possible pregnancy loss or delivery at a periviable gestational age around 23-25 weeks of gestation.23 
Other risks are those associated with anesthesia during the surgical procedure: hypotension, allergy to 
medications, headache. To limit these risks, the anesthetic route is typically regional anesthesia. Later 
on during the course of pregnancy, other risks maybe present as preterm contractions with the cerclage 
in place may cause laceration of the cervix and bleeding in which case the cerclage needs to be 
removed.  
Minor side effects include increased vaginal discharge, there is a theoretical disruption the vaginal flora 
associated with foreign object, and minimal discomfort at the time of cerclage removal.  
The potential benefits include prolongation of pregnancy, decreased very preterm delivery (< 28 weeks), 
very low birth weight (<1500 grams) and decreased in composite morbidity for the newborn (respiratory 
distress syndrome, need of intubation and mechanical ventilation, intraventricular hemorrhage, 
necrotizing enterocolitis, sepsis and retinopathy of the preterm newborn) and length of admission in the 
neonatal intensive care unit. Decreased perinatal mortality. These potential benefits are based on 
results of previous retrospective cohorts available in twin pregnancies. 
All of the investigators have received formal training on ultrasound indicated cerclage placement. The 
training and experience of the investigators will minimize the risks associated with cerclage placement. 

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Our protocol specifically states that the cervical cerclage will be removed if the patient goes into labor, 
has preterm premature rupture of membranes (PPROM), presents with active cervical bleeding, or if she 
remains asymptomatic and reaches 36 weeks of gestation.  
2 Study Objectives 
The overall objective of this study is to assess the efficacy of the use of ultrasound indicated cerclage for 
prevention of preterm birth in a population of women with twin gestations and TVU CL ≤ 15 mm prior to 
23 6/7 weeks. 
2.1 Primary Objective 
The primary objective of this study is to determine if ultrasound indicated cerclage reduces the 
incidence of spontaneous PTB before 34 weeks in asymptomatic women with twin gestations and TVU 
CL ≤ 15 mm between 16 0/7 to 23 6/7 weeks of gestation. 
2.2 Secondary Objective 
To determine if ultrasound indicated cerclage reduces the incidence of spontaneous PTB before 24, 28 
and 32 weeks in asymptomatic women with twin gestations and TVU CL ≤ 15 mm between 16 0/7 to 23 
6/7 weeks of gestation. 
To determine if ultrasound indicated cerclage reduces the neonatal mortality and morbidity in 
asymptomatic women with twin gestations and TVU CL ≤ 15 mm between 16 0/7 to 23 6/7 weeks of 
gestation. Neonatal morbidity will include any of the following (composite neonatal outcome): 
respiratory distress syndrome (grade 3 or 4), need for intubation and mechanically assisted ventilation, 
intraventricular hemorrhage (grade 3 or 4), necrotizing enterocolitis (grade 3 or 4), proven sepsis 
diagnosed by culture, retinopathy of the preterm newborn requiring laser treatment (grade 3 or 4) and 
length of stay in the intensive care unit. Neonatal mortality will include any death before discharge from 
the hospital. 
3 Study Design 
3.1 General Design 
This is a multi-center, open-label, randomized study. Women with twin gestations presenting for routine 
prenatal ultrasound between 16 to 23 6/7 weeks will be offered the option of having their cervical 
length measured as part of the standard of care for screening of preterm birth. Women with TVU CL ≤ 
25mm will be counseled about the risk of preterm birth and will be offered 400mg daily vaginal 
progesterone until 36 weeks of gestation. Those women with a cervix measuring ≤ 15mm will be invited 
to participate in the trial. Eligible subjects can be enrolled between 16 0/7 to 23 6/7 weeks gestation; 
subjects randomized to the use of the ultrasound indicated cerclage will have the procedure scheduled 
in the operating room under anesthesia. Decision to perform amniocentesis prior to the cerclage to rule 
out subclinical chorioamnionitis, surgical technique and suture type will be at the discretion of the 

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surgeon. Once the ultrasound indicated cerclage is in place, subjects will continue with their usual 
scheduled clinical prenatal visits, and will participate in the study until delivery. Cerclage will be 
removed during the 36th week of pregnancy on those asymptomatic women or earlier if indicated 
(preterm labor, PPROM, vaginal bleeding). Newborns will participate in the study until discharge home 
from the hospital. Information about pregnancy and neonatal outcomes will be obtained from medical 
records. 
3.2 Primary Study Endpoints 
Spontaneous preterm delivery at less than 34 weeks gestation 
3.3 Secondary Study Endpoints 
Secondary effectiveness endpoints: 
 
Gestational age at delivery 
 
Interval between diagnosis and delivery 
 
Birth weight of each neonate 
 
Spontaneous preterm birth rates at less than 24, 28, 32 and 37 weeks gestation 
 
Spontaneous rupture of membranes before 34 weeks gestation 
 
Secondary safety endpoints: 
 
Admission to the NICU and length of stay if admitted 
 
Neonatal death before discharge from hospital 
 
Composite adverse neonatal outcome (includes any of the following: necrotizing enterocolitis (grade 
3 or 4), Intraventricular hemorrhage (grade 3 or 4), respiratory distress syndrome (grade 3 or 4), 
need for intubation and mechanically assisted ventilation, retinopathy of the newborn requiring 
laser treatment (grade 3 or 4), and proven sepsis with positive culture). 
 
Clinical Chorioamnionitis  
 
Histological chorioamnionitis (It is standard of care to send placenta to pathology for multiple 
gestations).  
 
Significant adverse maternal effects including intraoperative rupture of membranes, bleeding, and 
cervical laceration (tear). 
 
4 Subject Selection and Withdrawal 
4.1 Inclusion Criteria 
1. Pregnant women more than 18 years of age (limits the participants to female gender) 
2. Diamniotic twin pregnancy  
3. Asymptomatic 
4. TVU CL ≤ 15 mm between 16-23 6/7 weeks gestation 
 

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4.2 Exclusion Criteria 
1. Singleton or higher order than twins multiple gestation  
2. TVU CL >16mm 
3. Cervical dilation with visible amniotic membranes  
4. Amniotic membranes prolapsed into the vagina 
5. Fetal reduction after 14 weeks form higher order  
6. Monoamniotic twins 
7. Twin-twin transfusion syndrome 
8. Ruptured membranes  
9. Major fetal structural anomaly 
10. Fetal chromosomal abnormality 
11. Cerclage already in place for other indication 
12. Active vaginal bleeding 
13. Clinical chorioamnionitis 
14. Placenta previa 
15. Painful regular uterine contractions 
16. Labor 
 
4.3 Subject Recruitment and Screening 
1. Potential study subjects will be identified at the time of a routine second trimester fetal ultrasound 
exam between 18 to 23 6/7 weeks gestation. All clinical sites have designated prenatal ultrasound 
units. Patients at all sites diagnosed with twin gestation will be offered transvaginal ultrasound 
cervical length for the screening of preterm birth. The initial consent to have a transvaginal 
ultrasound assessment of the cervical length will be a verbal consent as part of standard of care.  
2. Staff who will be performing screening TVU CL will be trained and certified through the Fetal 
Medicine Foundation https://fetalmedicine.org/training-n-certification/certificates-of-
competence/cervical-assessment-1  or CLEAR (https://clear.perinatalquality.org/).  
3. TVU CL technique: Endocervical canal length will be measured as the distance between the internal 
and external os using a vaginal probe at 6-MHz probe placed in the anterior fornix of the vagina. 
Three anatomic land- marks will define the appropriate sagittal view: the internal os, the external os 
and the endocervical canal. The image will be enlarged while visualizing the three landmarks 
simultaneously. Gentle pressure will be exerted on the cervix by the transducer followed by minimal 
pressure to allow visualization of the three landmarks. This procedure will be repeated three times 
and the shortest measurement will be recorded.24 
4. Women with TVU CL ≤ 25mm will be offered daily 400mg vaginal progesterone as standard of care 
based on recently published meta-analysis19  A repeat TVU CL will be offered a second time for those 
women with TVU CL 16 – 30 mm due to the concern for cervical length shortening over the next few 
weeks. 

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5. Women with TVU CL ≤15mm who will meet the inclusion criteria will be counselled by an 
obstetrician regarding the risk of SPTB as per standard of care. Only IRB approved research staff will 
approach eligible patients to assess interest in participating as well as to explain the trial. The 
patient will be given ample time to have all questions addressed and consider participation.  
6. Women with a TVU CL <10mm will be offered a speculum exam (pelvic exam). If the cervix is dilated 
and amniotic membranes are visible, women would not be eligible for randomization in this clinical 
trial. A digital cervical exam will not be done routinely.  
7. If the patient meets inclusion criteria and agrees to participate in the study, the informed consent 
form will be signed and a copy will be given to the patient.  
8. Women who are eligible and consent to participate in the study will be randomly assigned to one of 
two groups: cervical cerclage (i.e. intervention group) or no cerclage (i.e. control group). A web-
based system will be used to communicate the randomization assignments to the trial staff. Subjects 
will be randomized using blocks of randomly varying size (2, 4 and 6).  
9. For those patients assigned to cerclage, an insurance precertification process will be requested. 
After insurance approves the procedure, the cerclage will be scheduled in the operating room and it 
will be placed by one of the Maternal Fetal Medicine specialist and fellow.  
10. If patient declined participation and she is stable, she will continue outpatient bi-weekly or monthly 
prenatal care visits as per standard of care. 
11. If patient elects to have expectant management without randomization, we will ask for her 
authorization to address the research protocol at a different opportunity during her prenatal visits 
until 23 6/7 weeks, after that gestational age she is no longer eligible for participation. 

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5 Study  
5.1 Description 
Cervical cerclage is a suture/tape surgically placed around the cervix as close as possible to the high of 
the internal os. This suture is a non-absorbable sterile material  
5.2 Treatment Regimens 
Subjects will be randomized in a 1:1 fashion to either receive the ultrasound indicated cerclage, or 
expectant management. Women will still be able to withdrawal from the study after randomization if 
they feel that either expectant management or cerclage have an unacceptable risk of extreme 
premature delivery with increased risk of a severely handicap children. 
5.2.1 Ultrasound indicated cerclage 
For those randomized to ultrasound indicated cerclage placement, the surgical procedure will be 
scheduled in the main operating room under anesthesia.  
5.2.2 Expectant management 
For those randomized to expectant management, they will continue routine pregnancy care: daily 
vaginal progesterone and surveillance for signs of preterm labor.  
5.3 Method for Assigning Subjects to Treatment Groups 
A computer system will be used to communicate the randomization assignments to the trial staff. 
Subjects will be randomized centrally using blocks of randomly varying size (e.g, 2, 4 and 6). 
5.4 Placement of Cerclage 
Ultrasound indicated cerclage is placed by trained physician in the operating room under anesthesia 
(regional or general at the discretion of the anesthesiologist). Amniocentesis to evaluate for subclinical 
chorioamnionitis will be offered to every patient, declining amniocentesis doesn’t exclude subjects from 
participation in this trial. Amnioreduction (removal of larger amount of amniotic fluid), surgical 
technique, election of sutures, and admission to the hospital for observation or recommended amount 
of maternal physical activity after randomization will be at the discretion of the attending physician 
performing the cerclage. Women randomized to the cerclage group will receive indomethacin 50mg 
orally before the cerclage and for three additional doses postoperatively every 8 hours (at 8h, 16h, and 
24h after the cerclage). Women randomized to the cerclage group will also receive one dose of cefazolin 
1g IV (or 2g if >80kg) before the cerclage. 
6 Study Procedures 
6.1 Transvaginal cervical length measurement 

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Potential study subjects will be identified in the ultrasound room. Transvaginal ultrasound cervical 
length will be offered at the time of a routine second trimester fetal anatomy ultrasound exam between 
16-23 6/7 weeks gestation as part of standard of care practice for twin pregnancies, verbal consent will 
be requested prior to transvaginal ultrasound. 
 
6.2 Randomization 
Patients with TVU CL ≤ 15mm who are eligible and consent to participate in the study will be randomly 
assigned to one of two groups: Ultrasound indicated cerclage or no cerclage (standard expectant 
obstetric management). Subjects will be randomized using random block sizes of 2, 4 or 6. Patients 
allocated to the ultrasound indicated cerclage group will have the cerclage surgically placed. 
6.3 Interim Contacts 
Patients in both groups will be contacted by the research assistants monthly either by phone or in 
person at the time of their prenatal visit. The research assistants will ask the patients if they have had 
any complications with their pregnancy including any evaluations and/or admissions for preterm labor, 
vaginal bleeding, leaking of amniotic fluid, vaginal discharge and/or discomfort of if they received 
medications like antenatal steroids for fetal lung maturity, tocolysis or magnesium sulfate infusion. 
Consents for release of medical information will be signed at the time of randomization to gather 
medical information pertinent to the study in case of admissions to other institutions. 
Patients will be instructed to report any adverse symptoms including pain, vaginal bleeding, uterine 
contractions, decreased fetal movements and leakage of amniotic fluid immediately. They will be given a 
phone number to call if they have any questions or concerns about the study. A physician who is 
knowledgeable about the study will be available at all times. The study investigator will communicate 
with the patient’s primary obstetrician; ultrasound indicated cerclage placement will be done by one of 
the study investigators, but removal at any time during pregnancy can be done by the primary 
obstetrician. The primary obstetrician will be responsible for all prenatal care and delivery. 
6.4 Cerclage Removal 
The cerclage will be removed by the primary obstetrician during the 36th week of gestation if 
asymptomatic. Removal of cerclage can be performed in the office or triage room; there is no need of 
anesthesia. Indications for cerclage removal before this time include: active vaginal bleeding, persistent 
uterine contractions despite tocolysis, ruptured of amniotic membranes, and prolapsed membranes 
through the cervix / suture. 
6.5 Pregnancy Outcome 
After subjects have delivered, information regarding outcome of the pregnancy and neonatal outcome 
until discharge home will be abstracted from the subjects’ medical records. A release of medical records 
consent will be signed at the time of randomization, in case the patient delivers at an outside institution. 

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7 Statistical Plan 
7.1 Sample Size Determination 
Calculation of sample size was based on a reduction in the incidence of spontaneous delivery before 34 
weeks from 70% in the expectant management group to 50% in the cerclage group, with a power of 
80%. To detect this difference at a significance level of 5%, we will need to enroll a total of 186 subjects 
with 93 subjects in each arm, plus 10% for loss of follow up. Total 200 subjects with 100 subjects in each 
arm 
7.2 Statistical Methods 
The primary outcome is spontaneous preterm birth before 34 weeks of gestation. Secondary outcomes 
include gestational age at delivery, interval between diagnosis and delivery, birth weight, spontaneous 
preterm birth rates at less than 24, 28, 32 and 37 weeks gestation and spontaneous rupture of 
membranes at less than 34 weeks gestation. Secondary safety outcomes include admission to NICU, 
neonatal death, length of stay in the NICU until discharge home, composite adverse neonatal outcome 
that includes necrotizing enterocolitis (stage 3 or 4), intraventricular hemorrhage (grade 3 or 4), 
respiratory distress syndrome (grade 3 or 4), need of intubation and mechanical ventilation, retinopathy 
of prematurity requiring laser treatment (stage 3 or 4) and proven sepsis requiring treatment), and 
significant adverse maternal effects will include: intraoperative rupture of membranes, clinical or 
histological chorioamnionitis, postpartum hemorrhage, cervical tear and uterine rupture). Neonatal 
mortality prior to discharge home form the hospital.  
Statistical analysis will be based on the intention-to-treat principle. Comparisons between the two 
groups will be made with the Mann-Whitney U test. Univariate comparisons of dichotomous data will be 
performed with Fishers exact test. The p values for all hypotheses will be two sided, and p values of less 
than 0.05 will be considered to be significant. The risk of spontaneous preterm birth before 34 weeks 
will be quantified by use of the relative ratio and 95% confidence interval. Multivariate analysis will be 
performed using logistic regression. The risk of spontaneous preterm birth from randomization until 
delivery will be assessed with Kaplan-Meier analysis, in which gestational age is the timescale, 
spontaneous delivery is the event, and elective deliveries are censored. SPPS software package (version 
16.0) will be used for all statistical analyses.  
8 Safety and Adverse Events 
8.1 Definitions 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria: 
 
Unexpected in nature, severity, or frequency (i.e. not described in study-related documents such as 
the IRB-approved protocol or consent form, the investigators brochure, etc) 

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 
Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
 
Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
 
Unanticipated Adverse Surgical procedure Effect 
An Unanticipated Surgical procedure Effect is any serious adverse effect on health or safety, or any life-
threatening problem or death caused by, or associated with a surgical procedure, if that effect, problem, 
or death was not previously identified in nature, severity, or degree of incidence in the investigational 
plan or application (including a supplementary plan or application), or any other unanticipated serious 
problem associated with a  that relates to the rights, safety, or welfare of subjects. 
Serious injury 
Any injury or illness that is any one of the following: 
 
Life-threatening 
 
Results in permanent impairment of a body function or permanent damage to body structure 
 
Necessitates medical or surgical intervention to preclude permanent impairment of a body function 
or permanent damage to a body structure 
 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study. Intercurrent illnesses or injuries should be regarded as adverse events. 
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
 
Results in study withdrawal 
 
Is associated with a serious adverse effect related to the surgical procedure 
 
Is associated with clinical signs or symptoms 
 
Leads to additional treatment or to further diagnostic tests 
 
Is considered by the investigator to be of clinical significance 
 
 What will be monitored: 
Stopping rules: Any unanticipated effects and all adverse effects resulting in research subject death or 
injury will be reported to the PI immediately, no later than 10 days after the event and will include: 
1. Maternal sepsis with admission to ICU attributable to the cerclage placement 
2. Maternal death attributable to the cerclage placement 
3. Maternal bleeding requiring blood transfusion attributable to cerclage placement 

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4. Fetal and/or neonatal death or injury attributable to the cerclage placement  
 
Frequency of monitoring reports: after approximately 50% of the subjects have delivered 
 
8.2 Recording of Adverse Effects 
At each contact with the subject, the investigator must seek information on adverse effects by specific 
questioning and, as appropriate, by examination. Information on all adverse surgical procedure effects 
should be recorded immediately in the source document, and also in the appropriate adverse effect 
module of the case report form (CRF). All clearly related signs, symptoms, and abnormal diagnostic 
procedures results should recorded in the source document, though should be grouped under one 
diagnosis. 
All adverse effects occurring during the study period must be recorded. The clinical course of each event 
should be followed until resolution, stabilization, or until it has been determined that the study 
treatment or participation is not the cause. Serious adverse effects that are still ongoing at the end of 
the study period must be followed up to determine the final outcome. Any serious adverse effects that 
occur after the study period should be recorded and reported promptly (see section 8.3 below). 
The minimum initial information to be captured in the subject’s source document concerning the 
adverse effect includes: 
 
Study identifier 
 
Subject number 
 
A description of the event 
 
Date of onset 
 
Investigator assessment of the association between the event and study treatment 
 
Current status 
 
Whether study treatment was discontinued 
 
Whether the event is serious and reason for classification as serious 
 
8.3 Reporting of Adverse Effects and Unanticipated Problems 
8.3.1 Investigator reporting: Notifying the principal investigator 
Principal investigator and DSM person contact information for reporting purposes 
Report adverse effects by phone and facsimile to: 
 
Amanda Roman-Camargo, MD 
Email: amanda.roman@jefferson.edu 

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Phone: 215-955-9200 
Fax 215-955-5041 
 
Stuart Weiner, MD  
Email: Stuart.Weiner@jefferson.edu 
Phone: 215-955-9200 
Fax 215-955-5041 
 
Adverse Effects 
Any adverse effect that results in serious injury or death, and any type of unanticipated adverse effect, 
regardless of seriousness or severity, must be reported to the principal investigator by telephone within 
24 hours of the event. 
Within the following 48 hours, the principal investigator shall provide further information, as applicable, 
on the unanticipated adverse event or the unanticipated problem in the form of a written narrative. This 
should include a copy of the completed Unanticipated Problem form, and any other diagnostic 
information that will assist the understanding of the event. Significant new information on ongoing 
unanticipated adverse effects shall be provided promptly to the principal investigator. 
Deviations from the study protocol 
Deviations from the protocol must receive both principal investigator and the investigator’s IRB approval 
before they are initiated. Any protocol deviations initiated without principal investigator and the 
investigator’s IRB approval that may affect the scientific soundness of the study, or affect the rights, 
safety, or welfare of study subjects, must be reported to the Principal investigator and to the 
investigator’s IRB as soon as a possible, but no later than 5 working days of the protocol deviation. 
Withdrawal of IRB approval 
An investigator shall report to the principal investigator a withdrawal of approval by the investigator’s 
reviewing IRB as soon as a possible, but no later than 5 working days of the IRB notification of 
withdrawal of approval. 
8.3.2 Investigator reporting: Notifying the IRB 
Adverse Effects 
All unanticipated effects and all adverse effects resulting in research subject death or injury reported by 
the investigator to the study Principal investigator must also be reported to the investigator’s local IRB in 
accordance with their reporting requirements, though no later than 10 working days. 
Protocol Deviations 

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Any protocol deviations initiated without principal investigator and/or the investigator’s IRB approval 
that may affect the scientific soundness of the study, or affect the rights, safety, or welfare of study 
subjects, must be reported to the Principal investigator and to the investigator’s IRB as soon as a 
possible, but no later than 5 working days of the protocol deviation. 
Any adverse event that occurs any time during or after the research study, which in the opinion of the 
principal investigator is: 
 
Unexpected (An event is “unexpected” when its specificity and severity are not accurately reflected 
in the protocol-related documents, such as the IRB-approved research protocol, any applicable 
investigator brochure, and the current IRB-approved informed consent document  
 
AND 
 
Related to the research procedures (An event is “related to the research procedures” if in the 
opinion of the principal investigator, the event was more likely than not to be caused by the 
research procedures.) 
The above is required regardless of whether the event is serious or non-serious, on-site or off-site 
 
Adverse Effects 
All unanticipated effects and all adverse effects resulting in research subject death or injury must be 
reported to the investigator’s local IRB in accordance with their reporting requirements, though no later 
than 10 working days. 
Protocol Deviations 
Any protocol deviations initiated without principal investigator and/or IRB approval that may affect the 
scientific soundness of the study, or affect the rights, safety, or welfare of study subjects, must be 
reported to the investigator’s IRB as soon as a possible, but no later than 5 working days of the protocol 
deviation. 
Reporting Process 
Report unanticipated problems as defined above to the IRB office as a written report of the event 
(including a description of the event with information regarding its fulfillment of the above criteria, 
follow-up/resolution and need for revision to consent form and/or other study documentation). 
Copies of each report and documentation of IRB notification and receipt will be kept in the Clinical 
Investigator’s study file. 
Other Reportable events: 

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For clinical trials, the following events are also reportable to the IRB: 
 
Any adverse event that would cause the principal investigator to modify the protocol or informed 
consent form, or would prompt other action by the IRB to assure protection of human subjects. 
 
Information that indicates a change to the risks or potential benefits of the research, in terms of 
severity or frequency. For example: 
o An interim analysis indicates that participants have a lower rate of response to treatment 
than initially expected. 
o Safety monitoring indicates that a particular side effect is more severe, or more frequent 
than initially expected. 
o A paper is published from another study that shows that an arm of your research study is of 
no therapeutic value. 
 
Breach of confidentiality 
 
Change to the protocol taken without prior IRB review to eliminate apparent immediate hazard to a 
research participant. 
 
Incarceration of a participant when the research was not previously approved under Subpart C and 
the investigator believes it is in the best interest of the subject to remain on the study. 
 
Complaint of a participant when the complaint indicates unexpected risks or the complaint cannot 
be resolved by the research team. 
 
Protocol violation (meaning an accidental or unintentional deviation from the IRB approved 
protocol) that in the opinion of the investigator placed one or more participants at increased risk, or 
affects the rights or welfare of subjects. 
Unanticipated Adverse Effects 
Evaluation 
The principal investigator shall immediately evaluate each Unanticipated Adverse Effect. Such 
evaluations shall be reported to the IRB office, and participating investigators, within 10 working days 
after the principal investigator first receives notice of the effect. 
Unreasonable risk to subjects 
After evaluating an Unanticipated Adverse Effect, if the principal investigator determines the effect 
presents an unreasonable risk to subjects, the principal investigator shall terminate the study or parts of 
the study presenting that risk as soon as possible. Study termination shall occur no later than 5 working 
days after the principal investigator makes this determination and not later than 15 working days after 
the principal investigator first received notice of the effect.  
Withdrawal of IRB approval 

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The Principal investigator shall notify the IRB office and participating investigators of any withdrawal of 
approval of the study by a reviewing IRB within 5 working days after receipt of the withdrawal of 
approval. 
8.4 Medical Monitoring 
It is the responsibility of the principal Investigator to oversee the safety of the study. This safety 
monitoring will include careful assessment and appropriate reporting of adverse events as noted above, 
as well as the construction and implementation of a site data and safety-monitoring plan (see section 9 
Auditing, Monitoring and Inspecting). Medical monitoring will include a regular assessment of the 
number and type of adverse events. 
8.4.1 Data and Safety Monitoring Board 
An independent Data and Safety Monitoring Board (DSMB) will review data relevant to safety (not 
efficacy) after approximately 50% of the subjects have delivered. The DSMB will provide a 
recommendation as to whether the study should continue without modification of the protocol or 
informed consent. All unanticipated problems involving risks to participants or others will be reported 
by Dr. Amanda Roman to the head of the DSMB for this study 
 
9 Data Handling and Record Keeping 
9.1 Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements 
of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Those regulations require a 
signed subject authorization informing the subject of the following: 
 
What protected health information (PHI) will be collected from subjects in this study 
 
Who will have access to that information and why 
 
Who will use or disclose that information 
 
The rights of a research subject to revoke their authorization for use of their PHI. 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization. For 
subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 
permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study 
period. 
9.2 Source Documents 
Source data is all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in 

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source documents. Examples of these original documents, and data records include: hospital records, 
clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions 
certified after verification as being accurate and complete, microfiches, photographic negatives, 
microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, 
and at medico-technical departments involved in the clinical trial. 
9.3 Records Retention 
It is the principal investigator’s responsibility to retain study essential documents for at least 2 years 
after the last approval of a marketing application in their country and until there are no pending or 
contemplated marketing applications in their country or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents should be 
retained for a longer period if required by an agreement with the sponsor. In such an instance, it is the 
responsibility of the sponsor to inform the investigator/institution as to when these documents no 
longer need to be retained. 
10. Study Monitoring, Auditing, and Inspecting 
10.1 Study Monitoring Plan 
Research data will be reviewed by the study coordinator for correctness. Research charts will undergo 
periodic random audits to ensure the integrity of the data. The investigator will allocate adequate time 
for such monitoring activities. The Investigator will also ensure that the monitor or other compliance or 
quality assurance reviewer is given access to all the above noted study-related documents and study 
related facilities (e.g. pharmacy, diagnostic laboratory, etc.), and has adequate space to conduct the 
monitoring visit. 
10.2 Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the EC/IRB, 
government regulatory bodies, and University compliance and quality assurance groups of all study 
related documents (e.g. source documents, regulatory documents, data collection instruments, study 
data etc.). The investigator will ensure the capability for inspections of applicable study-related facilities 
(e.g. pharmacy, diagnostic laboratory, etc.). 
Participation as an investigator in this study implies acceptance of potential inspection by government 
regulatory authorities and applicable University compliance and quality assurance offices. 
11. Ethical Considerations 
This study is to be conducted according to US and international standards of Good Clinical Practice (FDA 
Title 21 part 312 and International Conference on Harmonization guidelines), applicable government 
regulations and Institutional research policies and procedures. 

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This protocol and any amendments will be submitted to a properly constituted independent Ethics 
Committee (EC) or Institutional Review Board (IRB), in agreement with local legal prescriptions, for 
formal approval of the study conduct. The decision of the EC/IRB concerning the conduct of the study 
will be made in writing to the investigator and a copy of this decision will be provided to the sponsor 
before commencement of this study. The investigator should provide a list of EC/IRB members and their 
affiliate to the sponsor. 
All subjects for this study will be provided a consent form describing this study and providing sufficient 
information for subjects to make an informed decision about their participation in this study. This 
consent form will be submitted with the protocol for review and approval by the EC/IRB for the study. 
The formal consent of a subject, using the EC/IRB-approved consent form, must be obtained before that 
subject undergoes any study procedure. The consent form must be signed by the subject or legally 
acceptable surrogate, and the investigator-designated research professional obtaining the consent. 
12. Conflict of Interest 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial 
gain greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by a 
properly constituted Conflict of Interest Committee with a Committee-sanctioned conflict management 
plan that has been reviewed and approved by the study sponsor prior to participation in this study.  
13. Publication Plan 
Neither the complete nor any part of the results of the study carried out under this protocol will be 
published or passed on to any third party without the consent of the principal investigator. Any 
investigator involved with this study is obligated to provide the principal investigator with complete test 
results and all data derived from the study. 
14. REFERENCES 
1. 
Martin JA, Hamilton BE, Osterman MJ, Driscoll AK, Mathews TJ. Births: Final Data for 2015. 
National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for 
Health Statistics, National Vital Statistics System 2017; 66(1): 1. 
2. 
Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. 
Lancet 2008; 371(9606): 75-84. 
3. 
Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Mathews TJ, Osterman MJ. Births: final data for 
2008. National vital statistics reports : from the Centers for Disease Control and Prevention, National 
Center for Health Statistics, National Vital Statistics System 2010; 59(1): 1, 3-71. 
4. 
Hamilton BE, Hoyert DL, Martin JA, Strobino DM, Guyer B. Annual summary of vital statistics: 
2010-2011. Pediatrics 2013; 131(3): 548-58. 
5. 
Meis PJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-
hydroxyprogesterone caproate. N Engl J Med 2003; 348(24): 2379-85. 
6. 
Owen J, Hankins G, Iams JD, et al. Multicenter randomized trial of cerclage for preterm birth 
prevention in high-risk women with shortened midtrimester cervical length. Am J Obstet Gynecol 2009; 
201(4): 375 e1-8. 

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7. 
Hassan SS, Romero R, Vidyadhari D, et al. Vaginal progesterone reduces the rate of preterm 
birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-
controlled trial. Ultrasound Obstet Gynecol 2011; 38(1): 18-31. 
8. 
Makrydimas G, Sotiriadis A. Prediction of preterm birth in twins. Best practice & research Clinical 
obstetrics & gynaecology 2014; 28(2): 265-72. 
9. 
Conde-Agudelo A, Romero R, Hassan SS, Yeo L. Transvaginal sonographic cervical length for the 
prediction of spontaneous preterm birth in twin pregnancies: a systematic review and metaanalysis. Am 
J Obstet Gynecol 2010; 203(2): 128 e1-12. 
10. 
Rouse DJ, Caritis SN, Peaceman AM, et al. A trial of 17 alpha-hydroxyprogesterone caproate to 
prevent prematurity in twins. N Engl J Med 2007; 357(5): 454-61. 
11. 
Norman JE, Mackenzie F, Owen P, et al. Progesterone for the prevention of preterm birth in twin 
pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis. Lancet 
2009; 373(9680): 2034-40. 
12. 
Rode L, Klein K, Nicolaides KH, Krampl-Bettelheim E, Tabor A, Group P. Prevention of preterm 
delivery in twin gestations (PREDICT): a multicenter, randomized, placebo-controlled trial on the effect 
of vaginal micronized progesterone. Ultrasound Obstet Gynecol 2011; 38(3): 272-80. 
13. 
Roman AS, Rebarber A, Pereira L, Sfakianaki AK, Mulholland J, Berghella V. The efficacy of 
sonographically indicated cerclage in multiple gestations. J Ultrasound Med 2005; 24(6): 763-8; quiz 70-
1. 
14. 
Roman A, Berghella V, Calluzzo I, Fleischer A, Rochelson B. 94: Ultrasound indicated cerclage in 
twin pregnancy. American Journal of Obstetrics and Gynecology 2014; 210(1, Supplement): S61. 
15. 
Berghella V, Odibo AO, To MS, Rust OA, Althuisius SM. Cerclage for short cervix on 
ultrasonography: meta-analysis of trials using individual patient-level data. Obstet Gynecol 2005; 106(1): 
181-9. 
16. 
Berghella V, Dugoff L, Ludmir J. Prevention of Preterm Birth with Pessary in Twins (PoPPT): a 
randomized controlled trial. Ultrasound Obstet Gynecol 2017. 
17. 
Saccone G, Ciardulli A, Xodo S, et al. Cervical pessary for preventing preterm birth in twin 
pregnancies with short cervical length: a systematic review and meta-analysis. J Matern Fetal Neonatal 
Med 2017: 1-8. 
18. 
El-refaie W, Abdelhafez MS, Badawy A. Vaginal progesterone for prevention of preterm labor in 
asymptomatic twin pregnancies with sonographic short cervix: a randomized clinical trial of efficacy and 
safety. Archives of gynecology and obstetrics 2016; 293(1): 61-7. 
19. 
Romero R, Conde-Agudelo A, El-Refaie W, et al. Vaginal progesterone decreases preterm birth 
and neonatal morbidity and mortality in women with a twin gestation and a short cervix: An updated 
meta-analysis of individual patient data. Ultrasound Obstet Gynecol 2017. 
20. 
Saccone G, Rust O, Althuisius S, Roman A, Berghella V. Cerclage for short cervix in twin 
pregnancies: systematic review and meta-analysis of randomized trials using individual patient-level 
data. Acta obstetricia et gynecologica Scandinavica 2015; 94(4): 352-8. 
21. 
Roman A, Rochelson B, Fox NS, et al. Efficacy of ultrasound-indicated cerclage in twin 
pregnancies. Am J Obstet Gynecol 2015; 212(6): 788 e1-6. 
22. 
Houlihan C, Poon LC, Ciarlo M, Kim E, Guzman ER, Nicolaides KH. Cervical cerclage for preterm 
birth prevention in twin gestation with short cervix: a retrospective cohort study. Ultrasound Obstet 
Gynecol 2016; 48(6): 752-6. 
23. 
Berghella V, Ludmir J, Simonazzi G, Owen J. Transvaginal cervical cerclage: evidence for 
perioperative management strategies. Am J Obstet Gynecol 2013. 

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24. 
Salomon LJ, Alfirevic Z, Berghella V, et al. Practice guidelines for performance of the routine mid-
trimester fetal ultrasound scan. Ultrasound Obstet Gynecol 2011; 37(1): 116-26. 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix #1: Initial Follow up 
Record ID __________________________________ 
Date of contact: __________________________________ 
Method of contact:  
 Email 
 Phone call 
 RedCap Survey 
 Text Message 
 Other: __________________________________ 
Name of person contacting participant: __________________________________ 
Have you experienced any complications with your pregnancy? [  ] Yes  [  ] No 
If yes, please describe: __________________________________ 
Have you been seen for a problem outside of a regularly scheduled prenatal visit? [  ] Yes  [  ] No 
Was this visit for: __________________________________ 
Have you been seen on labor and delivery, the labor and delivery triage unit, or the emergency room?     
[  ] Yes  [  ] No; if yes please describe: __________________________________ 
Have you experienced vaginal bleeding? [  ] Yes  [  ] No 
Have you experienced vaginal discharge? [  ] Yes  [  ] No 
Have you experienced contractions? [  ] Yes  [  ] No  
Have you experienced leaking of fluid? [  ] Yes  [  ] No 
Were you admitted to the hospital? [  ] Yes  [  ] No 
What dates were you admitted? _____________________________ 
For how many days? __________ 
Why were you admitted to the hospital? __________________________________ 
Were you treated with steroid shots for fetal lung maturity? [  ] Yes  [  ] No 
Were you treated with medication to stop preterm contractions or labor? [  ] Yes  [  ] No 
Was the cerclage removed? Why_____________________________________ 
Have you had sexual intercourse since you were enrolled in this study? [  ] Yes  [  ] No 
Additional notes/comments: __________________________________ 

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Appendix #2 Monthly Follow-Up 
Since our last contact with you, have you experienced any complications with your pregnancy?                 
[  ] Yes  [  ] No.  If yes, please describe: __________________________________ 
Since our last contact with you, have you been seen for a problem outside of a regularly scheduled 
prenatal visit? [  ] Yes  [  ] No 
Since our last contact with you, have you been seen on labor and delivery, the labor and delivery triage 
unit, or the emergency room? [  ] Yes  [  ] No . If yes please describe: ____________________________ 
Since our last contact with you, have you experienced vaginal bleeding? [  ] Yes  [  ] No 
Since our last contact with you, have you experienced vaginal discharge? [  ] Yes  [  ] No 
Since our last contact with you, have you experienced contractions? [  ] Yes  [  ] No 
Since our last contact with you, have you experienced leaking of fluid? [  ] Yes  [  ] No 
Were you admitted to the hospital? [  ] Yes  [  ] No 
Why were you admitted to the hospital? __________________________________ 
What dates were you admitted? __________________________________ 
If yes, for how many days? __________________________________ 
Were you treated with steroid shots for fetal lung maturity? __________________________________ 
Were you treated with medication to stop preterm contractions or labor? [  ] Yes  [  ] No 
Was the cerclage removed? Why______________________________________ 
Since our last contact with you, have you had sexual intercourse? [  ] Yes  [  ] No 
Additional notes/comments: __________________________________