- Email: [email protected]
Closing Discussion by Dr Edwards
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References 1. Goldberg AB, Greenberg BS, Darney PD. Misoprostol and pregnancy. N Eng J Med 2001;344:38-47. 2. Dickinson JE, Evans SF. The optimization of intravaginal misoprostol dosing schedules in second-trimester pregnancy termination. Am J Obstet Gynecol 2002;186:470-4.
DR EDWARDS (Closing statement). I appreciate the thorough review by Dr Devoe and his thoughtful comments. Regarding his first question, there were only 3 patients in the entire study whose gestational age was beyond 24 weeks. Since presenting the paper, we did reanalyze the induction to delivery intervals (survival curves, proportion delivered within 24 hours, and median times) within each treatment regimen, and did not see any significant differences related to gestational age. Likewise, there were no significant differences when comparing those patients whose indication was fetal anomaly versus all others. As we stated in our paper’s Comment, the increased rate of clinical chorioamnionitis in the high-dose group was an unexpected finding, and we have difficulty explaining this result. Certainly, as one performs more statistical tests upon a dataset, the chance of making a type I error increases. However, given the fact that we saw not only an increased rate of clinical chorioamnionitis but also histologic chorioamniontis in patients receiving the high-dose regimen, we think that a type I error is less likely. We hope that this outcome will be evaluated in other similar studies.
Edwards and Sims Dr Devoe asked whether we were planning to conduct a randomized clinical trial evaluating these 2 treatment regimens. Given the fact that this retrospective study spans almost 8 years, such a trial would be impractical unless it enrolled patients at several centers. Furthermore, we think that the data from this study are compelling enough to recommend the higher dose regimen. Finally, a randomized trial evaluating similar regimens has been conducted, and was part of the impetus for changing our guideline in 2002.1 Therefore, we have no plans to conduct such a clinical trial. Dr Devoe characterizes our discussion of the uterine rupture that occurred as minimizing the consequences of this complication. In no way did we mean to play down the morbidity that this complication entails for the pregnant woman. Our point was that uterine rupture during an attempt at second-trimester pregnancy termination did not also carry the risk of neonatal hypoxia and long-term neurologic morbidity. Although dilation and evacuation is associated with lower rates of morbidity and mortality, it is not available at many centers (ours is one). Therefore, effective methods of medical induction of labor in the second trimester are needed. We believe that the high-dose regimen of intravaginal misoprostol that we evaluated in this study, and that we are using in our practice, is one.
Reference 1. Dickinson JE, Evans SF. The optimization of intravaginal misoprostol dosing schedules in second-trimester pregnancy termination. Am J Obstet Gynecol 2002;186:470-4.
References 1. Goldberg AB, Greenberg BS, Darney PD. Misoprostol and pregnancy. N Eng J Med 2001;344:38-47. 2. Dickinson JE, Evans SF. The optimization of intravaginal misoprostol dosing schedules in second-trimester pregnancy termination. Am J Obstet Gynecol 2002;186:470-4.
DR EDWARDS (Closing statement). I appreciate the thorough review by Dr Devoe and his thoughtful comments. Regarding his first question, there were only 3 patients in the entire study whose gestational age was beyond 24 weeks. Since presenting the paper, we did reanalyze the induction to delivery intervals (survival curves, proportion delivered within 24 hours, and median times) within each treatment regimen, and did not see any significant differences related to gestational age. Likewise, there were no significant differences when comparing those patients whose indication was fetal anomaly versus all others. As we stated in our paper’s Comment, the increased rate of clinical chorioamnionitis in the high-dose group was an unexpected finding, and we have difficulty explaining this result. Certainly, as one performs more statistical tests upon a dataset, the chance of making a type I error increases. However, given the fact that we saw not only an increased rate of clinical chorioamnionitis but also histologic chorioamniontis in patients receiving the high-dose regimen, we think that a type I error is less likely. We hope that this outcome will be evaluated in other similar studies.
Edwards and Sims Dr Devoe asked whether we were planning to conduct a randomized clinical trial evaluating these 2 treatment regimens. Given the fact that this retrospective study spans almost 8 years, such a trial would be impractical unless it enrolled patients at several centers. Furthermore, we think that the data from this study are compelling enough to recommend the higher dose regimen. Finally, a randomized trial evaluating similar regimens has been conducted, and was part of the impetus for changing our guideline in 2002.1 Therefore, we have no plans to conduct such a clinical trial. Dr Devoe characterizes our discussion of the uterine rupture that occurred as minimizing the consequences of this complication. In no way did we mean to play down the morbidity that this complication entails for the pregnant woman. Our point was that uterine rupture during an attempt at second-trimester pregnancy termination did not also carry the risk of neonatal hypoxia and long-term neurologic morbidity. Although dilation and evacuation is associated with lower rates of morbidity and mortality, it is not available at many centers (ours is one). Therefore, effective methods of medical induction of labor in the second trimester are needed. We believe that the high-dose regimen of intravaginal misoprostol that we evaluated in this study, and that we are using in our practice, is one.
Reference 1. Dickinson JE, Evans SF. The optimization of intravaginal misoprostol dosing schedules in second-trimester pregnancy termination. Am J Obstet Gynecol 2002;186:470-4.