SUMMARY OF THE CURRENTLY AVAILABLE DATA
1. Prevention of PTL
The summary of data presented above indicates that administration
of progesterone in the second trimester to women
with short cervix or with a previous history of preterm
labour may reduce their risk for preterm birth. This modifies
the sole indication of PTL outlined in the ACOG technical
bulletin of 2003.25 The ACOG guideline cautiously
recommends the use of progesterone exclusively in women
with previous preterm labour.
2. Frequency of Use
The frequency of progesterone use based on the ACOG
recommendations increased in the US from 38% in 2003 to
67% in 2005.26 In contrast, a recent Canadian study27
showed that only 7% of Canadian obstetricians were using
progesterone for the prevention of PTL in 2004.
3. Neonatal Outcome
The use of progesterone contributes to a significant reduction
in low birth weight and intraventricular hemorrhage.
Further data are needed to demonstrate a significant reduction
in the following outcomes: perinatal death, respiratory
distress syndrome, necrotizing enterocolitis, patent ductus
arteriosus, sepsis, and retinopathy of prematurity, as the
current studies and the meta-analysis are underpowered to
detect effect on these parameters.
4. Safety
Progesterone has been used extensively and safely in the
first trimester, when the fetus is more vulnerable for luteal
phase insufficiency and recurrent losses. To date, no data
from RCTs and other studies for prevention of preterm
birth indicate this therapy is not safe aside from a single
retrospective study28 that showed that the incidence of gestational
diabetes was 12.9% in women treated with 17P
group (n = 557) compared with 4.9% in control subjects
(n = 1524, P < 0.001; OR 2.9 [95% CI 2.1–4.1]).
5. Route of Administration and Dosage
There are no data comparing routes of administration or
dosing regimens. The meta-analysis of Dodd et al.9 did not
show an added benefit of progesterone use prior to
20 weeks’ gestation. A recent RCT reached the same
conclusions.29
6. Need for Further Research
There are still large gaps in our knowledge. More data are
required to properly evaluate the impact on neonatal outcomes.
More information is needed on formulation (17
alpha-hydroxyprogesterone vs. progesterone), route of
administration (IM vs. vaginal or oral), and the optimal dosage
for progesterone use. More research is required to provide
definitive data on the potential rare risks associated with progesterone administration. Currently, there is at least
one RCT (The PROGRESS study) recruiting Canadian
patients at risk for PTL to evaluate vaginal administration of
progesterone for prevention of PTL