Clinical Review

Progesterone for preterm delivery prevention

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Three cases explore the questions of yay or nay and appropriate administration routes



Researchers have been studying the use of exogenous progestins for prevention of preterm delivery (PTD) for almost 60 years, but conflicting results contribute to an ongoing debate. Interpretation of the available data is particularly difficult because different forms and doses of progestins have been used in disparate study populations.

Based on available data, progesterone supplementation is not effective as a primary prevention strategy for PTD in the general low-risk obstetric population. PTD is a complex problem with varied and incompletely elucidated pathogenic pathways, making it unlikely that one interventional approach would be effective for all pregnant women. As a result, emerging indications for the use of progesterone are based on risk factors for PTD (ie, prior PTD and/or short cervix). However, this secondary prevention approach is a limiting factor in itself because 50% of women destined to have a PTD have no identifiable risk factors.1 In addition, researchers have found that progestins are ineffective at delaying delivery for women with multiple gestation, suggesting that a distinct underlying mechanism of early parturition is present in these women, and that this mechanism is unresponsive to progestins.2

The formulations used in the study of progestin supplementation for PTD prevention have been almost exclusively either the synthetic 17 alpha-hydroxyprogesterone caproate (17-OHPC) or natural progesterone administered orally or vaginally. In 2003, the American College of Obstetricians and Gynecologists (ACOG) supported the use of progesterone to reduce the rate of PTD,3 and in 2011, the US Food and Drug Administration (FDA) approved 17-OHPC for use as prophylaxis against recurrent PTD. As a result, in recent years, the perceived standard of care for a majority of practitioners in the United States had been that all women with a previous preterm birth should be offered 17-OHPC. It may be interesting to note that in other parts of the world, the same enthusiastic adoption did not occur. For example, in Australia and New Zealand in 2007, only 5% of practitioners were using progesterone for this indication.4 Further, 17-OHPC is not recommended by professional guidelines in the United Kingdom and has remained unavailable in Germany.

The publication in 2019 of the PROLONG trial called into question the use of 17-OHPC for the prevention of PTD.5 In the December 2019 issue of OBG Management (“Managing preterm birth in those at risk: Expert strategies”), I expressed the opinion that with only rare exceptions, 17-OHPC is no longer a viable option for recurrent PTD prevention.6 In light of these developments, what scientific evidence is relevant and applicable to the care of women at risk for PTD?

Continue to: Case 1 Previous spontaneous PTD at 31 weeks...


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