We would like to thank Professor Mol and Dr Byrne for their comments regarding our recent article, “17-Alpha-hydroxyprogesterone caproate does not prolong pregnancy or reduce the rate of preterm birth in women at high risk for preterm delivery and a short cervix: a randomized controlled trial.”

We acknowledge that our decision to stop the trial for futility at the interim analysis can be questioned. However, since the publication of Meis et al reporting that weekly injections of 17-alpha-hydroxyprogesterone caproate (17-OHPC) resulted in a substantial reduction in the rate of recurrent preterm delivery among women who have had a spontaneous preterm delivery, 9 other randomized trials (including ours) have been published, and all have failed to demonstrate any efficacy of 17OHP-C in the prevention of preterm birth.

Interestingly, the rate of recurrent preterm delivery among women who received placebo in the trial by Meis et al is astonishingly high (54.9%). In a recent report of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Consecutive Pregnancies Study, the rate of recurrent spontaneous preterm delivery was 31.6%. The high rate of preterm delivery in the placebo group of Meis et al might be attributable to the inclusion of a subset of women at particularly high risk for preterm delivery because of a history of early preterm birth, ethnic origin, or other confounding factor. These points raise concern about the external validity of the trial by Meis et al.

All in all, we agree that we cannot rule out the possibility that 17-OHPC does have a benefit but a much lower one than we hypothesized or that its efficacy is limited to a specific subset of high-risk women. Therefore, the question of whether we are stopping preterm birth trials too early can be answered only by a second randomized clinical trial of 17-OHPC vs placebo among women with a history of preterm delivery, as the Food and Drug Administration has requested, to determine whether the efficacy of 17-OHPC in the prevention of preterm birth can be replicated. Otherwise, questions about the efficacy of 17OHP-C will continue.