Progestogen for preventing miscarriage
Editorial Group: Cochrane Pregnancy and Childbirth Group
Published Online: 31 OCT 2013
Assessed as up-to-date: 3 SEP 2013
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Haas DM, Ramsey PS. Progestogen for preventing miscarriage. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD003511. DOI: 10.1002/14651858.CD003511.pub3.
- Publication Status: New search for studies and content updated (no change to conclusions)
- Published Online: 31 OCT 2013
Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilized egg. It has been suggested that a causative factor in many cases of miscarriage may be inadequate secretion of progesterone. Therefore, progestogens have been used, beginning in the first trimester of pregnancy, in an attempt to prevent spontaneous miscarriage.
To determine the efficacy and safety of progestogens as a preventative therapy against miscarriage.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 August 2013), reference lists from relevant articles, attempting to contact authors where necessary, and contacted experts in the field for unpublished works.
Randomized or quasi-randomized controlled trials comparing progestogens with placebo or no treatment given in an effort to prevent miscarriage.
Data collection and analysis
Two review authors assessed trial quality and extracted data.
Fourteen trials (2158 women) are included. The meta-analysis of all women, regardless of gravidity and number of previous miscarriages, showed no statistically significant difference in the risk of miscarriage between progestogen and placebo or no treatment groups (Peto odds ratio (Peto OR) 0.99; 95% confidence interval (CI) 0.78 to 1.24) and no statistically significant difference in the incidence of adverse effect in either mother or baby.
A subgroup analysis of placebo controlled trials did not find a difference in the rate of miscarriage with the use of progestogen (10 trials, 1028 women; Peto OR 1.15; 95% CI 0.88 to 1.50).
In a subgroup analysis of four trials involving women who had recurrent miscarriages (three or more consecutive miscarriages; four trials, 225 women), progestogen treatment showed a statistically significant decrease in miscarriage rate compared to placebo or no treatment (Peto OR 0.39; 95% CI 0.21 to 0.72). However, these four trials were of poorer methodological quality. No statistically significant differences were found between the route of administration of progestogen (oral, intramuscular, vaginal) versus placebo or no treatment. No significant differences in the rates of preterm birth, neonatal death, or fetal genital anomalies/virilization were found between progestogen therapy versus placebo/control.
There is no evidence to support the routine use of progestogen to prevent miscarriage in early to mid-pregnancy. However, there seems to be evidence of benefit in women with a history of recurrent miscarriage. Treatment for these women may be warranted given the reduced rates of miscarriage in the treatment group and the finding of no statistically significant difference between treatment and control groups in rates of adverse effects suffered by either mother or baby in the available evidence. Larger trials are currently underway to inform treatment for this group of women.
Plain language summary
Progestogen for preventing miscarriage
We could not find any evidence from randomized controlled trials that progestogen beginning in the first trimester of pregnancy can generally prevent miscarriage.
Hormones called progestogens prepare the womb (uterus) to receive and support the newly fertilized egg. It has been suggested that some women who miscarry may not make enough progesterone in the early part of pregnancy, so supplementing with progesterone has been suggested as a possible way to prevent miscarriage. This review of 14 randomized controlled trials (2158 women) found no evidence that progestogens can prevent miscarriage. No difference in the incidence of adverse effects on either the mother or baby were apparent. There was evidence, however, that women who have suffered three or more miscarriages may benefit from progestogen during pregnancy. Four trials showed a decrease in miscarriage compared with placebo or no treatment in these women, however, the trials were of poorer methodological quality so these findings should be interpreted with caution. No differences were found between the route of administration of progestogen (oral, intramuscular, vaginal) verus placebo or no treatment. More trials are needed and are under way to further clarify the effects in women with multiple prior miscarriages and to further clarify any impact on fetal anomalies.