Vaginal compared with intramuscular progestogen for preventing preterm birth in high-risk pregnant women (VICTORIA study): a multicentre, open-label randomised trial and meta-analysis.

OBJECTIVE: To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature. DESIGN: A multicentre, randomised, open-label, equivalence trial and a meta-analysis. SETTING: Tertiary referral hospitals in South Korea. POPULATION: Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm). METHODS: Eligible women were screened and randomised at 16-22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α-hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237). MAIN OUTCOME MEASURE: Preterm birth (PTB) before 37 weeks of gestation. RESULTS: A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention-to-treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI -7.6 to 13.8%), which was within the equivalence margin of 15%. The meta-analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments. CONCLUSION: Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length. TWEETABLE ABSTRACT: Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.

An imbalance in interleukin-17-producing T and Foxp3⁺ regulatory T cells in women with idiopathic recurrent pregnancy loss.

BACKGROUND: T cells which produce interleukin (IL)-17 are involved in chronic inflammatory processes and regulatory T (Treg) cells are possibly the most important immune regulators. We aimed to investigate peripheral blood IL-17(+) T and Foxp3(+) Treg cells in women with idiopathic recurrent pregnancy loss (RPL). METHODS: The study design is a cross-sectional evaluation of Th1, Th2, IL-17(+) T and Treg cells in women with idiopathic RPL (n = 42) and age-matched parous controls (n = 24). Flow cytometric analysis was performed to measure IL-17(+) T and Foxp3(+) Treg cells, and ratios of Th1/Th2 cells using anti-IL-17A and anti-Foxp3 antibodies, and monoclonal antibodies to tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-10. Student's t-test and partial correlations were applied for statistical analysis. RESULTS: TNF-α-/IL-10-producing CD3(+)CD4(+) T cell ratio was higher in women with RPL than controls (P = 0.048). Levels of IL-17(+) T cells (P = 0.021) and the IL-17(+) T/CD4(+)Foxp3(+) Treg cell ratio (P = 0.001) were increased, whereas Foxp3(+) (P = 0.035), Foxp3(low) (P = 0.032) and CD4(+)Foxp3(+) T cell (P = 0.037) levels were decreased in women with RPL, compared with controls. Levels of IL-17(+) T cells were correlated with TNF-α-producing CD3(+)CD4(+) T cells (r = 0.269, P = 0.033), and with ratios of TNF-α/IL-10 (r = 0.276, P = 0.027) and IFN-γ/IL-10 (r = 0.266, P = 0.035)-producing CD3(+)CD4(+) cells. Furthermore, the ratio of IL-17(+) T cells to CD4(+)Foxp3(+) Treg cells showed a positive correlation with TNF-α-producing CD3(+)CD4(+) T cells (P = 0.047) and IFN-γ-producing CD3(+)CD4(+) T cells (P = 0.048) as well as a ratio of IFN-γ/IL-10-producing CD3(+)CD4(+) T cells (P = 0.037). CONCLUSIONS: Enhanced pro-inflammatory immune responses with suppressed immune regulation may be an important immune mechanism involved in RPL.