The Impact of Vaginal and IM Progestins on the Cervix

University of Pittsburgh

Status: Completed

Conditions: Short Cervical Length; Preterm Birth

Study type: Observational

Funder types: Other

Identifiers

NCT01954095

OPRU Progestin

Details and patient eligibility

About

The purpose of this study is to analyze how the body handles and responds to progesterone treatment in parous and nulliparous women at risk of pre-term birth.

Full description

17-hydroxyprogesterone caproate (17-OHPC) has recently been shown to reduce the rate of recurrent preterm birth while intravaginal progesterone has been shown to reduce the rate of preterm birth in women with short cervix. While these interventions have reduced the rate of preterm birth, the mechanisms of action of these medications are unknown. The objective of this study is to collect and analyze blood and cervicovaginal fluids from pregnant women receiving these medications or other interventions such as cerclage, pessary, NSAIDs, and combinations thereof. The goal of the analyses is to assess the impact of these interventions on the cervical proteome, cervical cytokines and cervical structure and to identify potential biomarkers of response and non-response thus providing insights into the mechanisms of action of these drugs.

Enrollment: 89 patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

89 participants in 4 patient groups

Group 1: No prior preterm birth & normal cervix length

Description:

Pregnant women at 16 0/7 - 23 6/7 weeks gestation who have had one or more term births (no prior preterm births) and have a normal cervical length (\> 25 mm). These women will serve as gestational age controls for all groups.

Group 2: No prior preterm birth & short cervix length

Description:

Pregnant women at 16 0/7 - 23 6/7 weeks gestation who have no prior preterm births and have a short cervical length (20mm or less). These women may receive treatment (e.g. vaginal progesterone, cerclage, pessary, NSAIDs, or a combination thereof) or no treatment.

Group 3: Prior preterm birth, normal cervix length, 17-OHPC

Description:

Pregnant women at 16 0/7 - 23 6/7 weeks gestation who have had prior preterm birth, have a normal cervical length and will receive 17-OHPC treatment.

Group 4: Prior preterm birth, normal cervix length, no treat

Description:

Pregnant women at 16 0/7 - 23 6/7 weeks gestation who have had prior preterm birth, have a normal cervical length, and will not receive any treatment. These women will serve as controls for Group 3.