Oral dydrogesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: A double-blind, randomized, parallel, placebo-controlled trial

Abstract

Objective: To study the impact of administration of dydrogesterone in early pregnancy on pregnancy outcome and its correlation with Th1 and Th2 cytokine levels. Design: Double-blind, randomized, placebo-controlled study. Setting: A medical college and its associated hospital. Patient(s): Women with either: [1] a history of idiopathic recurrent pregnancy loss (RPL), in either a dydrogesterone group or a placebo group, or [2] no history of miscarriage. Intervention(s): Dydrogesterone 20 mg/day from confirmation of pregnancy to 20 weeks of gestation. Main Outcome Measure(s): Occurrence of another pregnancy loss and concentrations of T-helper (Th)1 (interferon-γ and tumor necrosis factor-α) and Th2 (interleukin (IL)-4 and IL-10) cytokines in serum at recruitment (4-8 weeks of gestation) and at abortion or 20 weeks of gestation, using commercially available ELISA kits. Result(s): Occurrence of another abortion after 3 consecutive abortions was significantly higher (29 of 173; 16.76%) in women with RPL compared with healthy pregnant controls (6 of 174; 3.45%). Risk of occurrence of miscarriage after 3 abortions was 2.4 times higher in the placebo group vs. the treatment group (risk ratio = 2.4, 95% CI = 1.3-5.9). Mean gestational age at delivery (excluding those aborted before 20 weeks of gestation) increased significantly in the dydrogesterone group (38.01 ± 1.96 weeks) compared with the placebo group (37.23 ± 2.41 weeks). Baby weight was significantly lower in the placebo group (2421.4 ± 321.6 g) compared with the healthy pregnant controls (2545.3 ± 554.3 g). At recruitment, serum IL-4 and tumor necrosis factor-α levels were significantly lower in the RPL group compared with the healthy pregnant controls. However, serum interferon-γ level was significantly higher in the RPL group (8.87 ± 0.72 pg/mL) compared with the healthy pregnant controls (8.08 ± 1.27 pg/mL). Conclusion(s): The present study supports the use of dydrogesterone in women with recurrent abortions to improve pregnancy outcome, such as a reduction in abortions and improved gestational age and baby weight at delivery. However, these outcomes were not modulated by Th1 and Th2 cytokine production. Clinical Trial Registration Number: CTRI/2010/091/000373.