The Impact of Vaginal and IM Progestins on the Cervix

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.

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