A Trial of Pessary and Progesterone for Preterm Prevention in Twin Gestation With a Short Cervix

Inclusion Criteria:

1. Twin gestation with cardiac activity in both fetuses. Higher order multifetalgestations reduced to twins, either spontaneously or therapeutically, are noteligible unless the reduction occurred by 13 weeks 6 days project gestational age.

2. Gestational age at randomization between 16 weeks 0 days and 23 weeks 6 days basedon clinical information and evaluation of the earliest ultrasound.

3. Cervical length on transvaginal examination of less than 30 mm by a study certifiedsonographer.

Exclusion Criteria:

1. Cervical dilation (internal os) 3 cm or greater on digital examination or evidenceof prolapsed membranes beyond the external cervical os either at the time of thequalifying cervical ultrasound examination or at a cervical exam immediately beforerandomization. There is no lower threshold of cervical length measurement thresholdon ultrasound that is an exclusion criterion.

2. Monoamniotic gestation, due to increased risk of adverse pregnancy outcome

3. Twin-twin transfusion syndrome, due to increased risk of adverse pregnancy outcome

4. Evidence of severe IUGR (intrauterine growth restriction) (<5th percentile forgestational age) in either fetus

5. Fetal anomaly in either twin or imminent fetal demise. This includes lethalanomalies, or anomalies that may lead to early delivery or increased risk ofneonatal death e.g., gastroschisis, spina bifida, serious karyotypic abnormalities).An ultrasound examination from 14 weeks 0 days to 23 weeks 6 days by project EDC (estimated date of conception) must be performed prior to randomization to evaluatethe fetuses for anomalies.

6. Placenta previa, because of risk of bleeding and high potential for indicatedpreterm birth

7. Active vaginal bleeding greater than spotting at the time of randomization, becauseof potential exacerbation due to pessary placement.

8. Symptomatic, untreated vaginal or cervical infection, also because of potentialexacerbation due to pessary placement. Patients may be treated and if subsequentlyasymptomatic, randomized.

9. Active, unhealed herpetic lesion on labia minora, vagina, or cervix due to thepotential for significant patient discomfort or increasing genital tract viralspread. Once lesion(s) heal and the patient is asymptomatic, she may be randomized.History of herpes is not an exclusion.

10. Rupture of membranes due to likelihood of pregnancy loss and preterm delivery aswell as the risk of ascending infection which could be increased with pessaryplacement

11. More than six contractions per hour reported or documented prior to randomization.It is not necessary to place the patient on a tocodynamometer

12. Known major Mullerian anomaly of the uterus (specifically bicornuate, unicornuate,or uterine septum not resected) due to increased risk of preterm delivery which isunlikely to be affected by progesterone

13. Any fetal/maternal condition which would require invasive in-utero assessment ortreatment, for example significant red cell antigen sensitization or neonatalalloimmune thrombocytopenia

14. Major maternal medical illness associated with increased risk for adverse pregnancyoutcome or indicated preterm birth (treated hypertension requiring more than oneagent, pre-gestational treatment for diabetes prior to pregnancy, chronic renalinsufficiency failure defined by creatinine >1.4 mg/dL, carcinoma of the breast,conditions treated with chronic oral glucocorticoid therapy. Specifically, patientswith seizure disorders, HIV, and other medical conditions not specificallyassociated with an increased risk of indicated preterm birth are not excluded. Priorcervical cone/LOOP/LEEP is not an exclusion criterion.

15. Planned cerclage or cerclage already in place since it would preclude placement of apessary

16. Planned indicated delivery prior to 35 weeks

17. Planned or actual progesterone treatment of any type or form after 15 weeks 6 daysduring the current pregnancy

18. Allergy to progesterone, silicone, or excipients in the study drug, includingpeanuts or peanut oil in the study drug or placebo

19. Known, suspected or history of breast cancer because breast cancer is acontraindication to the active study medication.

20. Known liver dysfunction or disease because liver disease is a contraindication tothe active study medication.

21. Participation in another interventional study that influences gestational age atdelivery or neonatal morbidity or mortality

22. Participation in this trial in a previous pregnancy. Patients who were screened in aprevious pregnancy, but not randomized, do not have to be excluded.

23. Prenatal care or delivery planned elsewhere unless the study visits can be made asscheduled and complete outcome information can be obtained