Efficacy and safety of misoprostol for intrauterine device insertion in women with no previous vaginal delivery: a systematic review and meta-analysis of randomized controlled trials

Introduction: The efficacy of misoprostol use for cervical priming before intrauterine device insertion (IUD) is controversial. This review aims to evaluate the evidence from published randomized controlled trials about the efficacy and safety of misoprostol before IUD insertion for pain relief in women with no previous vaginal delivery. Materials and methods: We searched the following electronic databases: Web of Science, Cochrane CENTRAL, SCOPUS, and PubMed for relevant studies using the following Mesh terms: (misoprostol) AND (intrauterine device OR IUD). The primary outcome was the mean pain score during insertion. Secondary outcomes included the ease of insertion score, the rate of successful IUD insertion, the rate of IUD insertion failure, and the adverse effects. Results: Ten randomized controlled trials (RCTs) (misoprostol: n=698 and placebo: n=689) were pooled in the analysis. The overall Standardized Mean Difference (SMD) of pain score did not favor either of the two groups (SMD= -0.09, 95%CI [-0.50, 0.33], p=0.007). Pooled results were highly heterogeneous (I2=93%, P<0.001). The total MD of the ease of insertion score favored the misoprostol group (MD= -1.36, 95% CI [-2.20, -0.52], p =0.002). The overall risk ratio (RR) of the number of failed insertions showed that misoprostol is associated with less IUD insertion failures compared to placebo (RR=0.55, 95% CI [0.38, 0.81], p=0.002). Finally, the overall risk showed that misoprostol is associated with more shivering, diarrhea and pelvic pain. Conclusions: Misoprostol facilitates IUD insertion in women with no previous vaginal delivery, and is associated with 50% less chance for IUD insertion failure despite inducing mild adverse effect

Does a history of malignancy impact the survival of a subsequent endometrial adenocarcinoma? Should clinical trials eligibility criteria be revisited?

We aimed at finding the impact of prior malignancies on the survival of patients with endometrial adenocarcinoma using SEER database (from 1973 to 2014). We identified 127,988 patients who were diagnosed with endometrial adenocarcinoma (6485 had a prior malignancy), and we compared the overall and cancer-specific survival based on the presence or absence of a prior malignancy and the latency period between the two diagnoses using Kaplan–Meier test and Cox models. Adjusted cox models showed that a history of a prior malignancy neither affected the overall survival nor the cancer-specific survival of stage IV cases in all latency groups except the one diagnosed within 1 year of the first cancer. Therefore, there is no rational explanation for excluding stage IV endometrial adenocarcinoma patients with a prior malignancy from clinical trials except for the group that was diagnosed with endometrial adenocarcinoma within 1 year from the first cancer.Impact statement What is already known on this subject? Not enough evidence is found on the impact of prior malignancies on the survival of patients with subsequent endometrial adenocarcinoma. What do the results of this study add? History of a prior malignancy neither affects the overall survival of stage IV endometrial adenocarcinoma nor the cancer-specific survival. Only patients who had their second malignancy diagnosed within one year of the first malignancy should be excluded from clinical trials, while patients diagnosed within one to five years of the first cancer should be encouraged to enrol in clinical trials as they have an enhanced survival than patients without a history of malignancy. What are the implications of these findings for clinical practice and/or further research? We recommend that future researchers should consider including the aforementioned group of patients in their trials to achieve more accurate results and in order not to strip the patients of potential therapeutic benefits of enrolling in clinical trials