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

Capsule:
Dydrogesterone supplementation in women with recurrent pregnancy loss improves ongoing pregnancy rates.

Authors:
Ashok Kumar, M.D., Ph.D., Nargis Begum, M.Sc., Ph.D., Sudha Prasad, M.D., Sarita Aggarwal, M.D., Shashi Sharma, Ph.D.

Volume 102, Issue 5, Pages 1357–1363.e3

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.

  • Reshef Tal

    Thank you for a very interesting randomized trial demonstrating
    impressive results in reducing miscarriage rates in RPL women following oral dydrogesterone treatment. I was very intrigued by the authors’ data on pregnancy outcomes following dydrogesterone treatment, showing reduced preterm birth and low-birth weight rates compared to the placebo group. There is a strong body of evidence
    from the Maternal Fetal Medicine Units Network that vaginal progesterone and intramuscular 17-OH progesterone caproate treatment reduce preterm birth in women with short cervix and history of preterm birth, respectively. These treatments are
    typically initiated between weeks 16 to 20 and given until 36 weeks. I found it
    remarkable that oral dydrogesterone supplementation given from 4-8 weeks of gestation up to only 20 weeks resulted in such an effect on preterm birth. What are the authors thoughts on this and do you think that extending dydrogesterone therapy to 36 weeks may show better efficacy in preterm delivery prevention? Also, since current evidence indicates that the progestogen formulation and method of
    administration seem to be important determinants of efficacy in reducing
    preterm birth risk, what do the authors think about a trial comparing the
    efficacy of oral dydrogesterone to vaginal/intramuscular progesterone?

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