Cervical cerclage placement decreases local levels of proinflammatory cytokines in patients with cervical insufficiency

Abstract

Background: Cervical insufficiency is characterized by premature, progressive dilation and shortening of the cervix during pregnancy. If left unattended, this can lead to the prolapse and rupture of the amniotic membrane, which usually results in midtrimester pregnancy loss or preterm birth. Previous studies have shown that proinflammatory cytokines such as interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor alpha are up-regulated in normal parturition but are also associated with preterm birth. Studies evaluating such markers in patients with cervical insufficiency have evaluated only their diagnostic potential. Even fewer studies have studied them within the context of cerclage surgery.

Objectives(s): The objective of the study was to evaluate the impact of local and systemic inflammatory markers on the pathogenesis of cervical insufficiency and the effect of cerclage surgery on the local immune microenvironment of women with cervical insufficiency.

Study design: We recruited 28 pregnant women (12-20 weeks' gestation) diagnosed with insufficiency and referred for cerclage surgery and 19 gestational age-matched normal pregnant women as controls. Serum and cervicovaginal fluid samples were collected before and after cerclage surgery and during a routine checkup for normal women and analyzed using a targeted 13-plex proinflammatory cytokine assay.

Results: Before surgery, patients with cervical insufficiency had higher levels of interleukin-1β, interleukin-6, interleukin-12, monocyte chemoattractant protein-1 and tumor necrosis factor alpha in cervicovaginal fluid compared to controls, but after surgery, these differences disappeared. No differences were found in serum of insufficiency versus control women. In patients with insufficiency, the levels of interleukin-1β, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, and interferon gamma in cervicovaginal fluid declined significantly after cerclage compared with before intervention, but these changes were not detected in serum.

Conclusion: Compared with normal women, patients with cervical insufficiency have elevated levels of proinflammatory cytokines in cervicovaginal fluid but not in serum, suggesting a dysregulation of the local immune environment. Cerclage intervention led to a significant decline in these proinflammatory cytokines, suggesting that cerclage may help reduce local inflammation in cervical insufficiency.

Keywords: McDonald’s cerclage; cervical fluid; cervical incompetence; cervical stitch; cervicovaginal fluid; cervix; chemokines; cytokines; inflammatory; interferon gamma; interleukin-1; interleukin-12; interleukin-6; interleukin-8; monocyte chemoattractant protein-1; pregnancy outcome; tumor necrosis factor alpha.