The Impact of Vaginal and IM Progestins on the Cervix

This study consists of 4 groups of women who are between 16 0/7 - 23 6/7 weeks gestation. The allocation of a subject to a group is based on two objective assessments (history of preterm birth and cervical length) and the joint clinical decision of the woman and her physician regarding treatment options.

Study participants who have no prior preterm births and a normal cervical length will be assigned to Group 1. If the participant has no prior preterm births and a short cervical length, she will be assigned to Group 2 regardless of treatment or no treatment. Group assignment for women with a prior preterm birth and normal cervical length is based on 17-OHPC use. Participants who elect to use 17-OHPC will be assigned to Group 3 and those who choose not to receive any treatment will be assigned to Group 4.

Inclusion Criteria

All Groups

• Singleton gestation (16 0/7 - 23 6/7 weeks gestation)
• Willing to provide informed consent
• Age 18 - 50 years inclusive

Additionally,

Group 1: One or more prior term births (>37 0/7 weeks); No prior spontaneous birth at 16 0/7 - 36 6/7 weeks; and normal cervical length (>25 mm)

Group 2: Cervical length of 20 mm or less at 16 0/7 - 23 6/7 weeks

Groups 3 and 4: History of prior spontaneous birth at 16 0/7 - 34 0/7 weeks and normal cervical length (> 25mm) at enrollment.

Exclusion Criteria

All Groups

• Active labor
• Active bleeding
• On progestin therapy, chronic steroid, or current NSAID therapy
• Actively receiving study treatment in another clinical trial (observational trials allowed)
• Major fetal malformation lethal anomalies, or anomalies that may lead to early delivery or increased risk of neonatal death e.g., gastroschisis, spina bifida, or serious karyotypic abnormalities
• Amniotic membranes prolapsed beyond the external os (ostium of uterus) or protruding into the vagina
• Pregnancy without a viable fetus
• Prenatal care or delivery planned elsewhere (unless the study visits can be made as scheduled and complete outcome information can be obtained)

Additionally:

Group 1: Cervical dilation greater than or equal to 3cm

Group 2: Prior preterm birth (16 0/7 - 34 0/7); active deep vein thrombosis, pulmonary embolism, or history of these conditions; known liver dysfunction or disease (active hepatitis, HIV)

Group 3: inability or unwillingness to use a 17-OHPC compounded product similar in composition to the FDA-approved product; allergy to 17-OHPC or its components

Groups 1, 3, and 4: cerclage in place or anticipated; congenital mullerian abnormality of the uterus; positive for bacterial vaginosis, chlamydia, gonorrhea, or trichomonas

Groups 3 and 4: current or history of thrombosis or thromboembolic disorders; known or suspected breast cancer, other hormone-sensitive cancer, or history of these conditions; undiagnosed abnormal vaginal bleeding unrelated to pregnancy; cholestatic jaundice of pregnancy, liver tumors, benign or malignant, or active liver disease; uncontrolled hypertension