Oral Micronized Progesterone Carries Higher Risk of Miscarriage, shows Meta-Analysis

Oral micronized progesterone carries the highest risk of miscarriage compared to oral dydrogesterone (DYD) and vaginal progesterone for the treatment of threatened miscarriage, a meta-analysis has reported. The study has been published in the International Journal of Gynecology & Obstetrics. 

The results have a far-reaching implication on the practice of pregnancy management and on the choice of drug for the prevention of threatened miscarriages, common complication during pregnancy known to occur in approximately 20% of all pregnancies.

Pregnancy is a special physiological condition with important physical and emotional changes that affect both maternal and fetus health. Drug treatment presents a special concern because the physiology of pregnancy affects the pharmacokinetics of medications used. One of the essential drugs for the maintenance of pregnancy is Progesterone which is widely worldwide in the therapeutic management of threatened abortion.

However, there is no clarity on the benefits of progesterone replacement therapy for women with threatened abortion; this may be due to the small size of previous studies, different routes of administration, different types of progesterone, and different outcomes.

There is a lack of comparative efficacy and safety between different types or routes of administration of progesterone, be it vaginal progesterone, oral micronized progesterone or dydrogesterone

With this background, Zhao et. al (2020) performed a meta-analysis to assess the efficacy and safety of various types of progestogens in the treatment of threatened miscarriage. They analyzed the online databases for randomized controlled trials (RCTs) published from the date of inception of the database to August 2020. It included all RCTs on threatened abortion so far that compared the efficacy and safety of different progestogens in the treatment of threatened abortion. 

The meta-analysis in the study included a total of 59 RCTs comprising of 10424 participants. Odds ratios for dichotomous data were calculated and the data were pooled using a random-effects model. The surface under the cumulative ranking area (SUCRA) was calculated for efficacy and safety with different interventions. 

Oral dydrogesterone was found to have the lowest risk of miscarriage (SUCRA 100.0%), followed by vaginal progesterone (SUCRA 67.9%). Oral micronized progesterone had the highest risk of miscarriage (SUCRA 15.7%) revealed by the meta-analysis.

The study showed, "when ranked from best/safest therapy, oral Dydrogesterone was first with SUCRA 100.0%, vaginal progesterone was second with SUCRA 67.9%, placebo and intramuscular progesterone had the same SUCRA rank suggesting a similar possibility of miscarriage (SUCRA 35.2% and 31.2%, respectively; both ranked as third best), and oral micronized progesterone was fourth (SUCRA 15.7%).

"The present meta-analysis showed that the miscarriage risk was lowest with the administration of oral Dydrogesterone followed by vaginal progesterone. Oral micronized progesterone had a higher risk of miscarriage," wrote the authors. The team noted that the treatment of preterm birth was noted to be safest with the administration of oral micronized progesterone and vaginal progesterone administration was shown to have the lowest congenital anomalies. 

To conclude, the study showed oral Dydrogesterone is effective for treating threatened miscarriages. The study results are helpful for patients and doctors in making an informed decision about treatment options for threatened miscarriage. 

References:

1. Dipali S. Sivasane, Rekha G. Daver. Study of pregnancy outcome of threatened abortion and its correlation with risk factors in a tertiary care hospital of Mumbai, India. 2018

2. Hongqiong Zhao, Wei He, Zhu Yang. A pairwise and network meta-analysis comparing the efficacy and safety of progestogens in threatened abortion. 2020. IJRCOG