Cerclage Plus Progesterone vs Progesterone Alone in Twin Short Cervix (VNTWINC)

Cervical Cerclage Plus Vaginal Progesterone Versus Vaginal Progesterone Alone in Twin Pregnancies With a Short Cervix for Prevention of Preterm Birth: a Randomized Controlled Trial

This study aims to compare the effectiveness of cervical cerclage combined with progesterone versus progesterone alone in preventing preterm birth among women with twin pregnancies and a short cervix (cervical length ≤ 30 mm). Participants will be randomly allocated to either the intervention group (cerclage plus progesterone) or the control group (progesterone alone).

Study Overview

• Status: Recruiting
• Conditions: Preterm
• Intervention / Treatment: Procedure: Cervical cerclage; Drug: Progesterone

Detailed Description

The incidence of multiple pregnancies has increased rapidly over the years mainly due to the resultant widespread use of assisted reproduction techniques. The twin birth rate in the USA has risen 70%, from 19 per 1000 live births in 1980 to 31 per 1000 live births in 2020. Twin pregnancies have a high risk on preterm birth (PTB) which is associated with increased risk of neonatal mortality and long-term morbidity. Around 60% of twin pregnancies deliver prior to 37 weeks and 12% before 34 weeks of gestation, with rates 5 and 8 times higher than the equivalent rates for a singleton pregnancy, respectively. Children born at an early gestational age are at increased risk of short-term morbidities affecting vital organ systems such as lungs, brain, bowels and are at increased risk of severe infection and sepsis. Perinatal mortality is strongly associated with extreme PTB. Survivors are at increased risk for developmental and behavioral disorders. In Vietnam, the rate of twin pregnancies deliver at < 28 weeks was about 11% in 2019. Caring for extremely premature infants is a significant burden for families and society. Therefore, obstetricians have a need for high-quality evidence for effective treatments.

Cervical length measurement (ideally transvaginal) is the preferred method of screening for preterm birth in twins; 25mm is a pragmatic cut-off between 18 and 24 gestational weeks (Grade of recommendation: C). Majority of the studies conducted previously has taken the cut-off cervical length as ≤ 25 mm. A systematic review and meta-analysis (13 retrospective studies and 3 RCTs) showed that cervical cerclage may reduce preterm birth in twin pregnancies with a cervical length <25 mm; however, preterm birth before 37, 34, and 28 weeks remained high (56.7%, 38.8%, and 11.7%, respectively)5, compared with much lower rates in singleton pregnancies (6.2%, 4.7%, and 0.4%). These findings support the need for further studies on preterm birth prevention in twin pregnancies with a cervical length >25 mm. In 2025, Yen et al. showed that cervical cerclage was more effective than pessary in twin pregnancies with a cervical length ≤28 mm, particularly in reducing preterm birth <28 weeks, with benefit observed at 25-28 mm. However, preterm birth rates remained high, suggesting that intervention at a higher cervical length threshold may be justified. Given gestational age-related cervical shortening and the substantially higher preterm birth risk in twins, a higher threshold corresponding to the 10th percentile (≤30 mm) has been proposed. Accordingly, we selected ≤30 mm as the intervention threshold in twin pregnancies.

In singleton pregnancies, vaginal progesterone is recommended as the primary intervention for pregnant women with a cervical length less than 25mm with consistently demonstrated effectiveness in preventing premature labor. In cases with a prior spontaneous preterm delivery and a short cervix, the placement of a vaginal cerclage should be considered. Conversely, there is less evidence on the optimal strategy for preventing PTB in twin pregnancies. In twins, IM 17- OHPC and cervical pessary are not indicated in order to prevent PTB. Evidence regarding the effectiveness of vaginal progesterone and cerclage remains unclear. Several randomized trials and systematic reviews reported little or no benefit of cerclage in twin pregnancies. However, these studies were limited by small sample size and large heterogeneity in their inclusion criteria, study populations, and outcomes observed. The data are insufficient to recommend for or against these interventions in the clinical circumstances. Moreover, in the a last few years, an increasing number of studies reporting a potential beneficial role of cerclage in reducing the risk of PTB and adverse outcomes in twin pregnancies have been published. The latest ISUOG practice guidelines (2025) stated that a combined strategy of physical-exam-indicated cerclage, antibiotics, and tocolytics may be considered in asymptomatic twin pregnancy with dilated cervix before 24 weeks of gestation and a cervical cerclage may be considered when the cervical length is ≤ 15 mm before 24 weeks of gestation (grade of recommendation: C). However, these findings are mainly based on observational studies and require confirmation in large and adequately powered RCTs.

In conclusion, there is a lack of well-designed RCT's on the effect of vaginal cerclage in asymptomatic twin pregnancies. We propose a multi-center randomized trial on the effectiveness of vaginal cerclage in women with a twin pregnancy and a short cervix (less than 30mm) in the second trimester with relevant outcomes assessing not only PTB at different cut-offs but also adverse maternal and neonatal outcomes.

This open label, multi-center, randomized controlled trial aims to compare the effectiveness of cervical cerclage combined with progesterone versus progesterone alone in preventing preterm birth among women with twin pregnancies with a cervix ≤ 30 mm.

Cervical length will be measured routinely in twin pregnancies between 16 and 24 weeks of gestation by qualified doctors via transvaginal ultrasound. Women with a cervical length ≤30 mm will be eligible for the study. Eligible participants will receive a Participant Information Sheet and provide written informed consent after discussion with the investigators. All eligible women will be invited to participate in the study.

Six centers are involved in the study and patients will be stratified by center. Patients will be randomly assigned in a 1:1 ratio to receive either cerclage plus progesterone or progesterone alone, using block randomization with a variable block size of 4, 6. To ensure allocation concealment, the random lists will be generated by www.sealedenvelope.com. Upon identification of an eligible participant, randomization data will be sequentially accessed an administrative staff who does not involve in clinical intervention. The random allocation will be conveyed to responsible clinicians. Due to the nature of interventions, the obstetricians and patients will not be blinded. Apart from randomization, patients will be managed and treated preterm birth (if present) according to local protocol.

In participants allocated to cerclage plus progesterone group, a Mersilene suture (Ethicon, LLC, United State) will be placed around the cervix in a purse-string fashion and securely tied anteriorly, following the McDonald technique under spinal anesthesia. The intervention needs to be performed before 24+0 weeks of gestation, by a team of dedicated obstetricians in our hospitals (2 to 3 obstetricians in each centers) to ensure the quality of the surgical procedure. For standardization of the cervical cerclage technique, all participating physicians received standardized training before study initiation. Prophylactic antibiotic: First/Second - generation Cephalosporin will be administered intravenously 1 hour before the procedure. In case of reporting an allergy to Cephalosporin, Clindamycin (Dalacin C® 600mg/4ml Pfizer, Belgium) will be used. Additional vaginal micronized progesterone will be administered at a total daily dose of 400 mg, given as Utrogestan® 200 mg (Besins Healthcare, France) twice daily, in the morning and at bedtime, from 2 days after receiving cerclage to 37+0/7 week of gestation or preterm birth whatever comes first.

In participants allocated to progesterone alone group, vaginal micronized progesterone will be administered at a total daily dose of 400 mg, given as Utrogestan® 200 mg (Besins Healthcare, France) twice daily, in the morning and at bedtime, from after randomization to 37+0/7 week of gestation or in case of preterm birth whatever comes first.

In both group, participants will be asked to record their vaginal progesterone application in a patient diary sheet for up to 140 days. At every visit, their compliance was documented by checking the diary and drug purchasing records from the hospital pharmacy. Compliance rate was calculated by dividing the number of progesterone doses used by the number of progesterone doses that should have been used since the last visit. Participants were considered compliant when their drugs used-to-prescribed rate was 80%.

Follow-up examination will be 7 days after randomization and then 2 weeks apart until delivery. At every exam, we perform routine antenatal care and CL measurement, record drug compliance and reveal any adverse events or complications. In case of premature rupture of the membranes, active vaginal bleeding, other signs of preterm labor, or severe discomfort of the participant, the use of cerclage and/or progesterone will be discontinued. Further treatment was indicated per local protocol. All interventions were terminated at 37 weeks or at delivery, whichever came first. Delivery will take place by either spontaneous onset of labor, induction of labor, or elective cesarean section according to national guidelines for twin pregnancies.

In cases where the patient delivers at hospitals that are not among the six study sites, data on neonatal and obstetric outcomes will be collected through telephone follow-up and medical record summaries obtained from the respective healthcare facilities.

The selected outcome measures correspond to the core outcome set established for studies on preterm birth prevention by GONet and the Core Outcomes in Women's Health initiative.

Hospital costs will be measured from hospital costs of patients and neonates.

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thu Ha T Nguyen, Assoc. Prof; Phone Number: 84965995599; Email: dr.hanguyen.nhog@gmail.com
• Study Contact Backup: Name: Viet C Dang, MD, MsC; Phone Number: 84346150993; Email: dangviethmu@gmail.com

Study Locations

• Vietnam
  • Bac Ninh, Vietnam, 220000
    • Not yet recruiting
    • Bac Ninh 1 Obstetrics and Pediatrics Hospital, Bac Ninh, Vietnam
    • Contact: Tuoc C Le, MD, MSc; Phone Number: 84983350133; Email: cachmangthanhcong@gmail.com
    • Contact: Hung V Dam, MD, MSC; Phone Number: 8485909334; Email: drhungsn@gmail.com
    • Sub-Investigator: Tuoc C Le, MD, MSc
  • Bac Ninh, Vietnam, 220000
    • Not yet recruiting
    • Bac Ninh 2 Obstetrics and Pediatrics Hospital, Bac Ninh, Vietnam
    • Contact: Bich Thanh T Nguyen, MD, MSc; Phone Number: 84912 585 033; Email: thanhbssan@gmail.com
    • Contact: My Hanh T Le, MD, MSC; Phone Number: 84389981505; Email: svquany@gmail.com
    • Sub-Investigator: Bich Thanh T Nguyen, MD, MSc
  • Hanoi, Vietnam, 100000
    • Recruiting
    • National Hospital of Obstetrics and Gynecology
    • Contact: Anh D Nguyen, Professor, MD, PhD, Director; Phone Number: 84985259999; Email: nguyenduyanh.nhog@gmail.com
    • Contact: Thu Ha T Nguyen, Assoc. Prof., Dep. Director; Phone Number: 84965995599; Email: dr.hanguyen.nhog@gmail.com
    • Principal Investigator: Viet C Dang, MD, MSc
    • Sub-Investigator: Anh T Ngo, MD, PhD
    • Sub-Investigator: Hung S Ho, Assoc. Prof., MD, PhD
    • Sub-Investigator: Hung Q Dang, MD, MSc
    • Sub-Investigator: Giang M Pham, MD, MSc
    • Sub-Investigator: Trac M Le, MD, PhD
    • Sub-Investigator: Trang M Nguyen, MSc
    • Principal Investigator: Anh D Nguyen, Professor, MD, PhD
    • Principal Investigator: Thu Ha T Nguyen, Assoc. Prof. MD, PhD
    • Sub-Investigator: Ben W Mol, Professor, MD, PhD
  • Hung Yen, Vietnam, 160000
    • Not yet recruiting
    • Hung Yen Obstetrics and Pediatrics Hospital, Hung Yen, Vietnam
    • Contact: Thanh Huyen T Vu, MD, MSc; Phone Number: 84978844859; Email: giamdoc2025f2@gmail.com
    • Contact: Thanh P Tran, MD, MSC; Phone Number: 84988102988; Email: drthanhtran102@gmail.com
    • Sub-Investigator: Thanh Huyen T Vu, MD, MSc
  • Ninh Binh, Vietnam, 430000
    • Not yet recruiting
    • Ninh Binh Obstetrics and Pediatrics Hospital, Ninh Binh, Vietnam
    • Contact: Dau V Pham, MD, MSc; Phone Number: 84912129565; Email: drdau70@gmail.com
    • Contact: Hue T Pham, MD, MSC; Phone Number: 84943706662; Email: dr.phamhue911@gmail.com
    • Sub-Investigator: Dau V Pham, MD, MSc
  • Quang Ninh, Vietnam, 200000
    • Not yet recruiting
    • Quang Ninh Obstetrics and Pediatrics Hospital, Quang Ninh, Vietnam
    • Contact: Cuong M Bui, MD, MSc; Phone Number: 84912356818; Email: buiminhcuong1975@gmail.com
    • Contact: Trang T Tran, MD, MSC; Phone Number: 84368479884; Email: hoatrangnguyen93yd@gmail.com
    • Sub-Investigator: Cuong M Bui, MD, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Maternal age ≥ 18
• Twin pregnancy
• Asymptomatic short cervix (CL≤30mm) at routine ultrasound investigation
• Gestational age at 16+0- 24+0 weeks

Exclusion Criteria:

A potential paticipant who meets any of the following criteria will be excluded from participation in this trial:

• Women with twin pregnancy in which one or both fetuses are diagnosed with a major structural or congenital abnormality that is likely to influence the composite adverse neonatal outcome.
• Women with a monochorionic monoamniotic twin pregnancy
• A monochorionic twin pregnancy with twin-to-twin transfusion syndrome before or at the time of inclusion.
• Patients have indications for vaginal cerclage: Recurrent late miscarriage (from 14 weeks) or preterm birth occurring two or more times.
• Women with dilatation of the cervix diagnosed by ultrasound or physical exam
• Women with overt symptoms of preterm labor at the time of measurement of the short cervix (regular contractions, PPROM, recurrent blood loss).
• Women with the presence of fever ≥ 38 degrees Celsius.
• Women with a placenta previa, vasa previa.
• Uterine malformations: unicornuate uterus, bicornuate uterus, uterine septum, fibroid…
• Severe maternal conditions (heart failure, chronic kidney disease, systemic lupus erythematosus …)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cerclage plus progesterone; Participants will receive cervical cerclage according to local protocols within one week after randomization. The procedure will be performed by three senior clinicians experienced in cerclage, using the McDonald technique. In addition, vaginal micronized progesterone will be administered at a total daily dose of 400 mg, given as Utrogestan® 200 mg (Besins Healthcare, France) twice daily, in the morning and at bedtime. Participants will be asked to record their vaginal progesterone application in a patient diary sheet for up to 140 days.	Procedure: Cervical cerclage; Participants will receive cervical cerclage according to local protocols within one week after randomization. The procedure will be performed by two to three senior clinicians experienced in cerclage in each center, using the McDonald technique.; Drug: Progesterone; Vaginal micronized progesterone will be administered at a total daily dose of 400 mg, given as Utrogestan® 200 mg (Besins Healthcare, France) twice daily, in the morning and at bedtime. Participants will be asked to record their vaginal progesterone application in a patient diary sheet for up to 140 days.; Other Names: Utrogestan 200mg
Active Comparator: Progesterone alone; Vaginal micronized progesterone will be administered at a total daily dose of 400 mg, given as Utrogestan® 200 mg (Besins Healthcare, France) twice daily, in the morning and at bedtime. Participants will be asked to record their vaginal progesterone application in a patient diary sheet for up to 140 days	Drug: Progesterone; Vaginal micronized progesterone will be administered at a total daily dose of 400 mg, given as Utrogestan® 200 mg (Besins Healthcare, France) twice daily, in the morning and at bedtime. Participants will be asked to record their vaginal progesterone application in a patient diary sheet for up to 140 days.; Other Names: Utrogestan 200mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preterm birth < 28 weeks	Number of participants with preterm birth before 28 weeks of gestation	From randomization until 27 6/7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestational age at birth	Number of completed weeks and days of gestation at the time of delivery, calculated based on the date of embryo transfer for pregnancies conceived via in vitro fertilization (IVF), or by ultrasound measurement of the crown-rump length (CRL) of the larger fetus between 11 weeks and 13 weeks 6 days of gestation, or by head circumference measurement for pregnancies beyond 14 weeks of gestation.	At birth
Preterm birth < 32 weeks	Number of participants with preterm birth before 32 weeks of gestation	From randomization until 31 6/7 weeks
Preterm birth < 34 weeks	Number of participants with preterm birth before 34 weeks of gestation	From randomization until 33 6/7 weeks
Preterm birth < 37 weeks	Number of participants with preterm birth before 37 weeks of gestation	From randomization until 36 6/7 weeks
Spontaneous preterm birth <28 weeks	Number of participants with spontaneous preterm birth before 28 weeks of gestation, including preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM)	From randomization until 27 6/7 weeks
Spontaneous preterm birth < 32 weeks	Number of participants with spontaneous preterm birth before 32 weeks of gestation, including preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM)	From randomization until 31 6/7 weeks
Spontaneous preterm birth < 34 weeks	Number of participants with spontaneous preterm birth before 34 weeks of gestation, including preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM)	From randomization until 33 6/7 weeks
Spontaneous preterm birth < 37 weeks	Number of participants with spontaneous preterm birth before 37 weeks of gestation, including preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM)	From randomization until 36 6/7 weeks
Iatrogenic preterm birth < 28 weeks	Number of participants with non-spontaneously before 28 weeks of gestation	From randomization until 27 6/7 weeks
Iatrogenic preterm birth < 32 weeks	Number of participants with non-spontaneously before 32 weeks of gestation	From randomization until 31 6/7 weeks
Iatrogenic preterm birth < 34 weeks	Number of participants with non-spontaneously before 34 weeks of gestation	From randomization until 33 6/7 weeks
Iatrogenic preterm birth < 37 weeks	Number of participants with non-spontaneously before 37 weeks of gestation	From randomization until 36 6/7 weeks
Preterm premature rupture of membranes	Number of participants diagnosed with preterm premature rupture of membranes (PPROM), defined as spontaneous rupture of membranes before 37 weeks of gestation and prior to the onset of labor. Diagnosis is based on clinical signs, including pooling of amniotic fluid in the vaginal vault.	From randomization until delivery, assessed up to 37 weeks of gestation
Hospital costs	Total hospital-related cost per participant, including: Direct medical costs (e.g., fees for consultations, medications, antenatal and delivery monitoring, treatment of complications related to cervical cerclage, and neonatal care during hospitalization)	From randomization to the time of hospital discharge of both the mother and the neonate(s), assessed up to 90 days after delivery
Maternal death	Death of the mother	From randomization until maternal hospital discharge, assessed up to 28 days after delivery
Composite of maternal adverse outcome	Number of participants who have any of the following maternal complications: chorioamnionitis, necrosis or rupture of the cervix, preterm premature rupture of the membranes, maternal death	From randomization until maternal hospital discharge, assessed up to assessed up to 28 days after delivery
Apgar score at 1 minute	Apgar score at 1 minute	Assessed at 1 minute after birth
Apgar score at 5 minutes	Apgar score at 5 minutes	Assessed at 5 minutes after birth
Apgar Score < 7 at 5 minutes	Apgar Score < 7 at 5 minutes	Assessed at 5 minutes after birth
Birthweight	The weight of the live-born infant measured in grams at birth	At birth
Number of neonates in need for respiratory supports	Number of neonates requiring respiratory support, including intubation, continuous positive airway pressure (CPAP), or high-flow nasal cannula (HFNC).	From delivery until neonatal hospital discharge, assessed up to 3 months corrected age
Length of ventilation	Number of days the neonate required respiratory support with mechanical ventilation (invasive or non-invasive), counted from the initiation of ventilation until final discontinuation.	From delivery until neonatal hospital discharge, assessed up to 3 months corrected age
Respiratory distress syndrome	Number of neonates diagnosed with respiratory distress syndrome (RDS), based on clinical signs (chest movement, intercostal retraction, xiphoid retraction, nasal flaring, expiratory grunt) and classified by Silverman score.	From delivery until neonatal hospital discharge, assessed up to 3 months corrected age
Admission to the neonatal intensive care unit	Number of neonates admitted to the neonatal intensive care unit (NICU)	From delivery until neonatal hospital discharge, assessed up to 3 months corrected age
Length of neonatal intensive care unit stay	Number of days of neonatal intensive care unit (NICU) stay	From admission to Neonatal Intensive Care Unit until neonatal hospital discharge or hospital referral, assessed up to 3 months corrected age
Length of neonatal admission	Total number of days of neonatal hospitalization, including stays in the neonatal intensive care unit (NICU) and the neonatal department	From delivery until neonatal hospital discharge, assessed up to 3 months corrected age
Neonatal infection	Number of neonates with the presence of a clinically ill infant in whom systemic infection is suspected with a positive blood, cerebrospinal fluid (CSF), or catheterized/supra-pubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an X-ray confirming infection	From delivery until neonatal hospital discharge, assessed up to 3 months corrected age
Neonatal seizures	Number of neonates with neonatal seizures	From delivery to neonatal hospital discharge, assessed up to 3 months corrected age
Intra-ventricular hemorrhage grades III and IV	Number of neonates diagnosed with grade III or IV intraventricular hemorrhage by ultrasonography	From delivery until neonatal hospital discharge, assessed up to 3 months corrected age
Necrotizing enterocolitis (NEC)	Number of neonates diagnosed with necrotizing enterocolitis (NEC) based on the clinical signs triad of abdominal distension, gastrointestinal bleeding, and pneumatosis intestinalis (air in bowel wall on abdominal X-ray) classified by Modified Bell's criteria.	From birth until neonatal hospital discharge, assessed up to 3 months corrected age
Neonatal sepsis	Number of neonates diagnosed with neonatal sepsis based on clinical signs (such as temperature instability, respiratory distress, lethargy, feeding difficulties) combined with laboratory evidence of infection (positive blood culture or other sterile site cultures) during the neonatal hospitalization period. The attending neonatologist confirms the diagnosis.	From birth until neonatal hospital discharge, assessed up to 3 months corrected age
Neonatal referred hospital transfer for severe morbidities	Number of neonates referred to other hospitals for severe morbidities	From birth until referral to another neonatal hospital, assessed up to 3 months corrected age
Stillbirth	Number of participants with stillbirth occurring at or after 28 weeks of gestation during the study period.	From randomization until delivery, assessed up to assessed up to 28 days after delivery
Neonatal deaths	Number of intrapartum, neonatal, and perinatal deaths	From birth until neonatal hospital discharge, assessed up to 3 months corrected age
Composite neonatal adverse outcome	Number of neonates who have any of the following neonatal outcome: neonatal sepsis, respiratory distress syndrome, intraventricular hemorrhage grade III and IV, necrotizing enterocolitis, perinatal death.	From birth until neonatal hospital discharge, assessed up to 3 months corrected age
Maternal side effects	Number of participants with at least one of the following: chorioamnionitis, severe bleeding, cervical necrosis, or cervical rupture	From randomization until delivery, assessed up to 28 days after delivery
Number of admission episodes for threatened preterm birth	Number of admission episodes for threatened preterm birth	From randomization until delivery, assessed up to 28 days after delivery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants having maternal post-partum blood transfusion	Number of participants having maternal post-partum blood transfusion	From delivery until maternal hospital discharge, assessed up to 28 days after delivery
Number of participants with hysterectomy	Hysterectomy for any postpartum complications	From delivery until maternal hospital discharge, assessed up to 28 days after delivery
Number of patients with TTTS after randomization	Number of patients diagnosed with twin-to-twin transfusion syndrome (TTTS) after randomization	From randomization until delivery, assessed up to 28 days after delivery
Number of participants diagnosed with TTTS after randomization who received treatment during the study period	Number of participants diagnosed with TTTS after randomization who received fetoscopic laser photocoagulation, serial amnioreduction, septostomy, selective reduction, or expectant management, from diagnosis until delivery	From randomization until delivery, assessed up to 28 days after delivery
Number of patients with preeclampsia	Number of patients diagnosed with preeclampsia	From randomization until delivery, assessed up to 28 days after delivery
Number of participants diagnosed with gestational diabetes mellitus (GDM) who required insulin therapy during the study period	Number of participants diagnosed with gestational diabetes mellitus (GDM) who required insulin therapy during the study period	From randomization until delivery, assessed up to 28 days after delivery
Length of hospital stay for treatment of threatened preterm birth	Cumulative duration of hospital stay for treatment of threatened preterm birth (days)	From randomization until 36 6/7 weeks
Number of participants diagnosed with congenital anomalies after randomization	Number of participants diagnosed with congenital anomalies after randomization during the study period	From randomization until delivery, assessed up to 28 days after delivery
Number of participants with rupture of the cervix during labor related to prior cerclage	Number of participants with rupture of the cervix during labor related to prior cerclage	From randomization until delivery, assessed up to 28 days after delivery
Number of participants diagnosed with chorioamnionitis	Number of participants diagnosed with chorioamnionitis, defined as clinical intra-amniotic infection based on maternal fever (≥38.0°C) and at least two of the following criteria: uterine tenderness, fetal tachycardia (>160 beats per minute), maternal tachycardia (>100 beats per minute), foul-smelling amniotic fluid, or maternal leukocytosis (>15 × 10⁹/L).	From randomization until delivery, assessed up to 28 days after delivery
Number of participants with vaginal delivery	Number of participants with vaginal delivery	From randomization until delivery, assessed up to 28 days after delivery
Number of participants with maternal infection	Number of participants with fever (defined as a temperature ≥37.5 degrees Celsius), start of intravenous broad-spectrum antibiotics (with evidence of infection confirmed by clinical and subclinical presentation), endometritis, myometritis or urinary tract infection	From randomization until maternal hospital discharge, assessed up to 28 days after delivery
Number of participants admitted to intensive care unit	Number of participants admitted to intensive care unit	From randomization until maternal hospital discharge, assessed up to 28 days after delivery
Length of intensive care unit stay	Number of days in intensive care unit stay	From randomization until maternal hospital discharge, assessed up to 28 days after delivery
Number of neonates requiring cardiopulmonary resuscitation (CPR) at birth	Defined as the number of live-born neonates who received cardiopulmonary resuscitation (CPR) immediately after birth, including interventions such as positive pressure ventilation, chest compressions, and/or administration of medications, as per neonatal resuscitation guidelines.	From delivery to 72 hours postnatal
Reason for Neonatal Intensive Care Unit admission	Reason for Neonatal Intensive Care Unit admission such as: respiratory distress, hypoglycemia, seizures, etc	From delivery until Neonatal Intensive Care Unit discharge, assessed up to 3 months corrected age
Length of neonatal hospital stay	Total number of days from birth until hospital discharge for each live-born neonate.	From delivery until neonatal hospital discharge, assessed up to 3 months corrected age
Number of neonates with neonatal infection	Number of neonates with presence of a clinically ill infant in whom systemic infection is suspected with a positive blood, cerebrospinal fluid (CSF), or catheterized/supra-pubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an X-ray confirming infection	From delivery until neonatal hospital discharge, assessed up to 3 months corrected age
Number of neonates with neonatal seizures	Number of neonates with neonatal seizures	From delivery to neonatal hospital discharge, assessed up to 3 months corrected age
Number of neonates with hypoglycemia	Number of neonates with hypoglycemia	From delivery until neonatal hospital discharge, assessed up to 3 months corrected age
Number of neonates referred to other hospitals for severe morbidities	Number of neonates referred to other hospitals for severe morbidities	From delivery until neonatal hospital referral, assessed up to 3 months corrected age
Number of participants with post-partum hemorrhage	Defined as blood loss >500 ml at vaginal birth or >1000 ml at caesarean birth within 24 hours after birth	Within 24 hours from delivery
Number of participants with uterine rupture	Number of participants with uterine dehiscence (defined as clinically asymptomatic disruption of the uterus that is discovered incidentally at surgery) or rupture (defined as clinically significant rupture involving the full thickness of the uterine wall and requiring surgical repair)	From delivery until maternal hospital discharge, assessed up to 28 days after delivery
Number of participants with other post-partum complications	Number of participants with at least one of the following: venous embolism, pulmonary embolism, stroke, or cardiac arrest	From randomization until maternal hospital discharge, assessed up to 28 days after delivery
Number of participants referred to other hospital due to severe morbidities	Number of participants referred to another hospital due to severe morbidities, including pulmonary embolism, stroke, and cardiorespiratory arrest.	From randomization until maternal hospital referral, assessed up to 28 days after delivery
Postpartum blood transfusion volume	Total volume of blood products (in milliliters) transfused to the participant after delivery, including packed red blood cells, whole blood, or other blood components, recorded from delivery until hospital discharge.	From delivery until maternal hospital discharge, assessed up to 28 days after delivery

Collaborators and Investigators

• Sponsor: National Hospital of Obstetrics and Gynecology
• Collaborators: Quang Ninh Obstetrics and Pediatrics Hospital, Quang Ninh, Vietnam; Ninh Binh Obstetrics and Pediatrics Hospital, Ninh Binh, Vietnam; Bac Ninh 1 Obstetrics and Pediatrics Hospital, Bac Ninh, Vietnam; Bac Ninh 2 Obstetrics and Pediatrics Hospital, Bac Ninh, Vietnam; Hung Yen Obstetrics and Pediatrics Hospital, Hung Yen, Vietnam
• Investigators: Study Chair: Anh D Nguyen, Prof, MD,PhD, National Hospital of Obstetrics and Gynecology

Publications and helpful links

General Publications

• Akar B, Ceylan Y, Kahraman A, Kole E, Caliskan E. Centile charts of cervical length in singleton and twin pregnancies between 16 and 24 weeks of gestation. J Turk Ger Gynecol Assoc. 2023 Jun 7;24(2):114-119. doi: 10.4274/jtgga.galenos.2023.2022-7-3. Epub 2023 Mar 31.
• He YTN, Pham HNH, Nguyen TC, Bui TQ, Vuong NT, Nguyen DTN, Le TV, Li W, Le CH, Ho TM, Mol BW, Dang VQ, Vuong LN. Cervical cerclage versus cervical pessary with or without vaginal progesterone for preterm birth prevention in twin pregnancies and a short cervix: A two-by-two factorial randomised clinical trial. PLoS Med. 2025 Feb 21;22(2):e1004526. doi: 10.1371/journal.pmed.1004526. eCollection 2025 Feb.
• van 't Hooft J. A core outcome set for evaluation of interventions to prevent preterm birth: summary for CROWN. BJOG. 2016 Apr;123(5):666. doi: 10.1111/1471-0528.14003. No abstract available.
• van 't Hooft J, Duffy JMN, Daly M, Williamson PR, Meher S, Thom E, Saade GR, Alfirevic Z, Mol BWJ, Khan KS; Global Obstetrics Network (GONet). A Core Outcome Set for Evaluation of Interventions to Prevent Preterm Birth. Obstet Gynecol. 2016 Jan;127(1):49-58. doi: 10.1097/AOG.0000000000001195.
• D'Antonio F, Eltaweel N, Prasad S, Flacco ME, Manzoli L, Khalil A. Cervical cerclage for prevention of preterm birth and adverse perinatal outcome in twin pregnancies with short cervical length or cervical dilatation: A systematic review and meta-analysis. PLoS Med. 2023 Aug 3;20(8):e1004266. doi: 10.1371/journal.pmed.1004266. eCollection 2023 Aug.
• Wu FT, Chen YY, Chen CP, Sun FJ, Chen CY. Outcomes of ultrasound-indicated cerclage in twin pregnancies with a short cervical length. Taiwan J Obstet Gynecol. 2020 Jul;59(4):508-513. doi: 10.1016/j.tjog.2020.05.007.
• Freegard GD, Donadono V, Impey LWM. Emergency cervical cerclage in twin and singleton pregnancies with 0-mm cervical length or prolapsed membranes. Acta Obstet Gynecol Scand. 2021 Nov;100(11):2003-2008. doi: 10.1111/aogs.14255. Epub 2021 Sep 2.
• Roman A, Zork N, Haeri S, Schoen CN, Saccone G, Colihan S, Zelig C, Gimovsky AC, Seligman NS, Zullo F, Berghella V. Physical examination-indicated cerclage in twin pregnancy: a randomized controlled trial. Am J Obstet Gynecol. 2020 Dec;223(6):902.e1-902.e11. doi: 10.1016/j.ajog.2020.06.047. Epub 2020 Jun 25.
• Conde-Agudelo A, Romero R, Nicolaides K, Chaiworapongsa T, O'Brien JM, Cetingoz E, da Fonseca E, Creasy G, Soma-Pillay P, Fusey S, Cam C, Alfirevic Z, Hassan SS. Vaginal progesterone vs. cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis. Am J Obstet Gynecol. 2013 Jan;208(1):42.e1-42.e18. doi: 10.1016/j.ajog.2012.10.877. Epub 2012 Nov 15.
• Jarde A, Lutsiv O, Park CK, Barrett J, Beyene J, Saito S, Dodd JM, Shah PS, Cook JL, Biringer AB, Giglia L, Han Z, Staub K, Mundle W, Vera C, Sabatino L, Liyanage SK, McDonald SD. Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis. BJOG. 2017 Jul;124(8):1163-1173. doi: 10.1111/1471-0528.14513. Epub 2017 Feb 8.
• D'Antonio F, Berghella V, Di Mascio D, Saccone G, Sileo F, Flacco ME, Odibo AO, Liberati M, Manzoli L, Khalil A. Role of progesterone, cerclage and pessary in preventing preterm birth in twin pregnancies: A systematic review and network meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2021 Jun;261:166-177. doi: 10.1016/j.ejogrb.2021.04.023. Epub 2021 Apr 24.
• Prediction and Prevention of Spontaneous Preterm Birth: ACOG Practice Bulletin, Number 234. Obstet Gynecol. 2021 Aug 1;138(2):e65-e90. doi: 10.1097/AOG.0000000000004479.
• van Gils L, Dutilh R, Denswil N, Roman A, de Boer MA, Pajkrt E, Oudijk MA. The effectiveness of ultrasound-indicated cerclage for the reduction of extreme preterm birth in twin pregnancies with a short cervix: a systematic review and meta-analysis. Am J Obstet Gynecol MFM. 2025 Jan;7(1):101555. doi: 10.1016/j.ajogmf.2024.101555. Epub 2024 Nov 26.
• Khalil A, Sotiriadis A, Baschat A, Bhide A, Gratacos E, Hecher K, Lewi L, Salomon LJ, Thilaganathan B, Ville Y. ISUOG Practice Guidelines (updated): role of ultrasound in twin pregnancy. Ultrasound Obstet Gynecol. 2025 Feb;65(2):253-276. doi: 10.1002/uog.29166. Epub 2025 Jan 15. No abstract available.
• Dang VQ, Nguyen LK, Pham TD, He YTN, Vu KN, Phan MTN, Le TQ, Le CH, Vuong LN, Mol BW. Pessary Compared With Vaginal Progesterone for the Prevention of Preterm Birth in Women With Twin Pregnancies and Cervical Length Less Than 38 mm: A Randomized Controlled Trial. Obstet Gynecol. 2019 Mar;133(3):459-467. doi: 10.1097/AOG.0000000000003136.
• Litwinska E, Syngelaki A, Cimpoca B, Frei L, Nicolaides KH. Outcome of twin pregnancy with two live fetuses at 11-13 weeks' gestation. Ultrasound Obstet Gynecol. 2020 Jan;55(1):32-38. doi: 10.1002/uog.21892. Epub 2019 Dec 13.
• Osterman M, Hamilton B, Martin JA, Driscoll AK, Valenzuela CP. Births: Final Data for 2020. Natl Vital Stat Rep. 2021 Feb;70(17):1-50.

Study record dates

Study Major Dates

• Study Start (Estimated): April 10, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): May 30, 2029

Study Registration Dates

• First Submitted: January 9, 2026
• First Submitted That Met QC Criteria: January 19, 2026
• First Posted (Actual): January 28, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Progesterone; Twin pregnancy; cervical cerclage
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Surgical Procedures, Operative; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Gonadal Steroid Hormones; Gonadal Hormones; Pregnenediones; Pregnenes; Obstetric Surgical Procedures; Corpus Luteum Hormones; Progesterone Congeners; Progesterone; Cerclage, Cervical; Utrogestan
• Other Study ID Numbers: NHOG-VN.TWIN CERCLAGE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No