Cerclage and Progesterone for Twin Pregnancies

Combined Cervical Cerclage and Vaginal Progesterone May Readjust the Deregulated Cervicovaginal Fluid Inflammatory Milieu and Improve Outcomes of Twin Pregnant Women

Twin pregnancies face a high risk of complications, most notably preterm birth (delivery before 37 weeks), which is a major cause of infant death and illness globally. For women carrying twins who are identified as having a short cervical length (cervix measuring 25 millimeters or less), there is currently no single, highly effective preventative treatment. This study is a randomized clinical trial designed to determine if a combined therapy of Cervical Cerclage (a surgical stitch to support the cervix) and Vaginal Progesterone (a hormone medication) is more effective than standard care in preventing preterm birth and improving the overall health outcomes for both the mother and the babies. The trial will also investigate the biological basis of this effect by measuring specific inflammation markers (cytokines like Interleukin-1$\beta$, 6, 8, and Tumor Necrosis Factor-α) in the cervical fluid before and after the intervention, to see if the combined treatment helps to reduce harmful local inflammation.

Study Overview

• Status: Completed
• Conditions: Twin Pregnancy With Antenatal Problem
• Intervention / Treatment: Procedure: McDonald Cervical Cerclage; Drug: Vaginal Progesterone Therapy (VPT)

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Qalyubia Governorate
    • Banhā, Qalyubia Governorate, Egypt, 13511
      • Faculty of Medicine, Benha University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Type of Pregnancy: Women with confirmed twin pregnancy (TP).
• Cervical Length: Short cervical length (CL) defined as ≤25 mm.
• Timing of Diagnosis: Short cervix detected via transvaginal ultrasound (TVU) at 11-13 weeks + 6 days, or detected during bi-weekly follow-up exams until 23 weeks + 6 days.
• Consent: Participants willing to undergo randomization and comply with the follow-up protocol.

Exclusion Criteria:

• Multiple Gestation (High Order): Triplet or higher-order pregnancies.
• Fetal/Uterine Complications: Polyhydramnios, premature rupture of membranes (PPROM), or known uterine abnormalities.
• Acute Symptoms: Vaginal bleeding, fever, or signs of fetal distress.
• Maternal Comorbidities: Pre-existing or gestational hypertension, and diabetes mellitus.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cervical Cerclage (CC); Participants in this arm undergo a McDonald cerclage technique. This involves placing a purse-string suture (No. 1 or 2 braided or monofilament) around the cervix to close the internal os. The suture is typically removed at 37 weeks of gestation.	Procedure: McDonald Cervical Cerclage; The procedure involves exposing the cervix and grasping it with ring forceps. A purse-string suture using No. 1 or 2 braided or monofilament material is placed at the 12 o'clock position with a curved needle. The needle is inserted at the junction of the vaginal epithelium and the cervix, approximately 2 cm above the external os and distal to the vesicocervical reflection. After 5-6 cautious bites, the stitch is pulled tight to close the internal os. The suture is typically removed at 37 weeks of gestation, provided there is no labor or membrane rupture.
Active Comparator: Vaginal Progesterone Therapy (VPT); Participants receive 100 mg vaginal progesterone inserts (e.g., Endometrin) administered twice daily. This treatment continues until spontaneous labor occurs or until the 37th week of pregnancy.	Drug: Vaginal Progesterone Therapy (VPT); Participants receive 100 mg vaginal progesterone inserts. Dosage & Frequency: One 100 mg insert administered twice daily. Duration: The treatment continues until the onset of spontaneous labor or until the 37th week of pregnancy.
Active Comparator: Combined Therapy (CC/VPT); Participants receive both the surgical Cervical Cerclage procedure and the daily Vaginal Progesterone inserts as described in the individual arms above.	Procedure: McDonald Cervical Cerclage; The procedure involves exposing the cervix and grasping it with ring forceps. A purse-string suture using No. 1 or 2 braided or monofilament material is placed at the 12 o'clock position with a curved needle. The needle is inserted at the junction of the vaginal epithelium and the cervix, approximately 2 cm above the external os and distal to the vesicocervical reflection. After 5-6 cautious bites, the stitch is pulled tight to close the internal os. The suture is typically removed at 37 weeks of gestation, provided there is no labor or membrane rupture.; Drug: Vaginal Progesterone Therapy (VPT); Participants receive 100 mg vaginal progesterone inserts. Dosage & Frequency: One 100 mg insert administered twice daily. Duration: The treatment continues until the onset of spontaneous labor or until the 37th week of pregnancy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success Rate of Treatment Regimens in Preventing Preterm Birth and/or Improving Pregnancy Duration	The proportion of patients who achieved a pregnancy duration of 37 weeks or more and/or significantly delayed delivery, reflecting the effectiveness of the administered treatment regimens (Cervical Cerclage, Vaginal Progesterone, or Combined Therapy) in high-risk twin pregnancies.	6-7 Months

Collaborators and Investigators

• Sponsor: Benha University

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2023
• Primary Completion (Actual): August 24, 2024
• Study Completion (Actual): June 14, 2025

Study Registration Dates

• First Submitted: December 20, 2025
• First Submitted That Met QC Criteria: December 20, 2025
• First Posted (Actual): January 6, 2026

Study Record Updates

• Last Update Posted (Actual): January 6, 2026
• Last Update Submitted That Met QC Criteria: December 20, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: Rc 4.12.2022

Drug and device information, study documents

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