What now? A critical evaluation of over 20 years of clinical and research experience with 17-alpha hydroxyprogesterone caproate for recurrent preterm birth prevention

Spontaneous preterm birth is multifactorial, and underlying etiologies remain incompletely understood. Supplementation with progestogens, including 17-alpha hydroxyprogesterone caproate has been a mainstay of prematurity prevention strategies in the United States in the last 2 decades. Following a recent negative confirmatory trial, 17-alpha hydroxyprogesterone caproate was withdrawn from the US market and is currently available only through clinical research studies. This expert review summarized clinical and research data regarding the use of 17-alpha hydroxyprogesterone caproate in the United States from 2003 to 2023 for recurrent prematurity prevention. In 17-alpha hydroxyprogesterone caproate. The history of the use, mechanisms of action, clinical trial results, and efficacy by clinical and biologic criteria of 17-alpha hydroxyprogesterone caproate are presented. We report that disparate findings and conclusions between similarly designed rigorous studies may reflect differences in a priori risk and population incidence and extreme care should be taken in interpreting the studies and making decisions regarding efficacy of 17-alpha hydroxyprogesterone caproate for the prevention of preterm birth. The likelihood of improved obstetrical outcomes after receiving 17-alpha hydroxyprogesterone caproate may vary by clinical factors (eg, body mass index), plasma drug concentrations, and genetic factors, although the identification of individuals most likely to benefit remains imperfect. It is crucial for the medical community to recognize the importance of preserving the decades-long efforts invested in preventing recurrent preterm birth in the United States. Moreover, it is important that we thoroughly and thoughtfully evaluate 17-alpha hydroxyprogesterone caproate as a promising contender for future well-executed prematurity studies.