http://apps.who.int/rhl/reviews/CD003511.pdfFifteen trials (2118 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) 0.98; 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. In a subgroup analysis of three trials involving women who had recurrent miscarriages (three or more consecutive miscarriages), progestogen treatment showed a statistically significant decrease in miscarriage rate compared to placebo or no treatment (Peto OR 0.38; 95% CI 0.20 to 0.70). No statistically significant differences were found between the route of administration of progestogen (oral, intramuscular, vaginal) versus placebo or no treatment.
Authors’ conclusions
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.
Birthweight
One study (Gerhard 1987 ) studied birthweight. It reported no
incidence of a baby born weighing less than 2500 gm. Two other
studies also reported birthweight but provided a mean rangerather
than individual data (Corrado 2002 ; Nyboe Anderson 2002 ).
There were no statistically significant differences in the mean
weight of babies in either study.
Fetal abnormalities
Four studies reported fetal abnormalities as an outcome
(El-Zibdeh 2005; Gerhard 1987; Reijnders 1988; Le Vine 1964).
Two studies reported no incidence of fetal abnormalities (Gerhard
1987; Le Vine 1964). One study reported a single case of fetal genital abnormality in the progestogen group (Reijnders 1988). There
was no statistically significant difference in fetal genital anomalies
(Peto OR 7.64; 95% CI 0.15 to 385.21). One study reported two anomalies in the progestogen group (neural tube defect and nonimmune hydrops) and one case of multiple anomalies in the control group in a baby with Down’s syndrome (El-Zibdeh 2005 ). No genital anomalies were noted in that study. In addition, the three arms of Moller et al (Moller 1965a; Moller 1965b; Moller 1965c) reported one case of fetal abnormality in the progestogen group but, due to inconsistency in the method used for reporting numbers, could not be included in the meta-analysis. (That is, in total there were 131 successful pregnancies and 139 live births. The numbers for successful pregnancies are divided into progestogen and placebo groups. However, the live births are not separated in this manner. The one baby with fetal abnormalities is given in the figures for live births rather than successful pregnancies).
D I S C U S S I O N
The aim of this review was to assess the effectiveness of progestogens to prevent miscarriage. Although there has been much speculation that progestogens may reduce the miscarriage rate, the
results of this meta-analysis show no statistically significant difference between women receiving progestogen and those receiving only placebo or no treatment, when no provision is made for
obstetric history. Subgroup analysis by method of administration (oral, intramuscular or vaginal) also showed no statistically significant difference between progestogen and placebo groups.
However, when provision was made for obstetric history, by way of a subgroup analysis only including women who had suffered three or more consecutive miscarriages directly prior to the studied pregnancy, a statistically significant difference was found in favor of the progestogen group. This finding should be approached with caution, however, as numbers are small. Two trials are currently underway to further evaluate therapy in this subgroup of women.
The meta-analysis showed no statistically significant difference in the number of fetal abnormalities (including virilisation and hypospadias) in babies whose mothers had been given progestogens
whilst in vitro, nor in intrauterine death/still birth or neonatal death.
There has been much discussion as to whether progestogen may prevent preterm birth (Keirse 1990 ). There was no statistically significant difference in our meta-analysis between the number
of preterm births in the progestogen and placebo groups. However, it is important to note that this systematic review only assesses progestogen given in early pregnancy to prevent miscarriage,
rather than trials assessing progestogen given in the second or third trimester to try to prevent preterm delivery.
No studies reported adverse maternal effects.
A U T H O R S ’ C O N C L U S I O N S
Implications for practice
There is no evidence to support the routine use of progestogen to prevent miscarriage in early to mid-pregnancy.
Implications for research
A finding of a significantly reduced miscarriage rate in women with a history of recurrent miscarriage (three or more consecutive miscarriages) deserves further study.