Abstract
ObjectiveTo determine the effect of intramuscular progesterone on the vaginal immune response of pregnant women with a history of prior preterm birth.MethodsA prospective, cohort study of women at 11–16 weeks gestation, ≥18 years of age, and carrying a singleton pregnancy was conducted from June 2016 to August 2017 after IRB approval. Women in the progesterone arm had a history of preterm birth and received weekly intramuscular 17-hydroxyprogesterone caproate. Controls comprised of women with healthy, uncomplicated pregnancies. Excluded were women with vaginitis, diabetes mellitus, hypertension, or other chronic diseases affecting the immune response. A vaginal wash was performed at enrollment, at 26–28 weeks, and at 35–36 weeks gestation. Samples underwent semi-quantitative detection of human inflammatory markers. Immunofluorescence pixel density data was analyzed and a P value <0.05 was considered significant.ResultsThere were 39 women included, 10 with a prior preterm birth and 29 controls. The baseline demographics and pregnancy outcomes for both groups were similar in age, parity, race, BMI, gestational age at delivery, mode of delivery, and birth weight. Enrollment cytokines in women with a prior preterm birth, including IL-1 alpha (39.2±25.1% versus 26.1±13.2%; P = 0.04), IL-1 beta (47.9±26.4% versus 24.9±17%; P<0.01), IL-2 (16.7±9.3% versus 11.3±6.3%; P = 0.03), and IL-13 (16.9±12.4% versus 8.2±7.4%; P = 0.01) were significantly elevated compared to controls. In the third trimester the cytokine densities for IL-1 alpha (26.0±18.2% versus 22.3±12.0%; P = 0.49), IL-1 beta (31.8±15.9% versus 33.1±16.8%; P = 0.84), IL-2 (10.0±8.4% versus 10.9±5.9%; P = 0.71), and IL-13 (9.1±5.9% versus 10.0±6.5%; P = 0.71) were all statistically similar between the progesterone arm and controls, respectively.ConclusionThere is an increased cytokine presence in vaginal washings of women at risk for preterm birth which appears to be modified following the administration of 17- hydroxyprogesterone caproate to levels similar to healthy controls.
Highlights
Intramuscular progesterone, administered to women at risk of preterm birth, reduces the likelihood of a subsequent preterm birth by approximately one-third [1,2]
The baseline demographics and pregnancy outcomes for both groups were similar in age, parity, race, body mass index (BMI), gestational age at delivery, mode of delivery, and birth weight
Enrollment cytokines in women with a prior preterm birth, including IL-1 alpha (39.2±25.1% versus 26.1±13.2%; P = 0.04), IL-1 beta (47.9±26.4% versus 24.9±17%; P
Summary
Intramuscular progesterone, administered to women at risk of preterm birth, reduces the likelihood of a subsequent preterm birth by approximately one-third [1,2]. The exact mechanism of action of progesterone therapy in preventing preterm birth is not well understood [3]. Due to an increase in myometrial PR-A, there is a functional withdrawal of progesterone and an increase in sensitivity to contractile stimuli [3]. This effect is modulated by prostaglandins produced prior to the onset of labor [3]. Progesteronedependent immunomodulation is another plausible mechanism that enables pregnancy to proceed to term. Progesterone-induced blocking factor, synthesized by lymphocytes of healthy pregnant women in the presence of progesterone, inhibits natural killer cell (NK) activity and modifies the cytokine balance [5]. Pretreatment with progesterone prior to intrauterine infection has been associated with a decrease in bacteriainduced upregulation of Toll-like receptors in the cervix and placenta [8]
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