The study showed no benefit for use of misoprostol prior to IUD insertion. However, there is a tendency of possible harm regarding side-effects. Therefore, we would not recommend standard pretreatment with misoprostol. The trial was registered in the European Clinical Trials Database EudraCT 2006-006897-60.

Immunotherapy of usual vulvar intraepithelial neoplasia (uVIN) is promising; however, many patients still fail to show clinical responses, which could be explained by an immune escape through alterations in human leukocyte antigen (HLA) expression. Therefore, we analyzed a cohort of patients with a primary (n 5 43) and subsequent recurrent uVIN lesion (n 5 20), vaccinetreated uVIN patients (n 5 12), patients with human papillomavirus (HPV)-induced vulvar carcinoma (n 5 21) and healthy controls (n 5 26) for the expression of classical HLA-class I/II and nonclassical HLA-E/-G and MHC class I chain-related molecule A (MICA). HLA-class I was downregulated in 70% of uVIN patients, including patients with a clinical response to immunotherapy. Downregulation of HLA-class I is probably reversible, as only 15% of the uVIN cases displayed loss of heterozygosity (LOH) and HLA-class I could be upregulated in uVIN keratinocyte cultures by interferon c. HLA-class I downregulation is more frequently associated with LOH in vulvar carcinomas (25-55.5%). HLA-class II was found to be focally expressed in 65% of uVIN patients. Of the nonclassical molecules, MICA was downregulated in 80% of uVIN whereas HLA-E and -G were expressed in a minority of cases. Their expression was more prominent in vulvar carcinoma. No differences were found between the alterations observed in paired primary and recurrent uVIN. Importantly, downregulation of HLA-B/C in primary uVIN lesions was associated with the development of recurrences and progression to cancer. We conclude that downregulation of HLA is frequently observed in premalignant HPV-induced lesions, including clinical responders to immunotherapy, and is associated with worse clinical outcome. However, in the majority of cases downregulation may still be reversible.Usual vulvar intraepithelial neoplasia (uVIN) is a chronic premalignant skin condition with an increasing incidence mainly in young women, which is caused by a persistent high-risk human papillomavirus (HPV) infection in more than 90% of cases.1,2 uVIN causes complaints of severe and long-lasting pruritis, pain and sexual dysfunction and has a malignant potential of 3-4% in treated and of 9% in untreated patients.1,3 Because conventional treatments for uVIN are characterized by high recurrence rates of 20-40% and psychosexual problems, there is a need for alternative therapies. [4][5][6] Failure of the immune system to induce a strong and effective immune response to HPV is known to cause

PurposeThe aim of the study was to compare the prophylactic effects of carbetocin with those of oxytocin for the prevention of uterine atony in patients undergoing elective caesarean section (CS) in the Netherlands. The primary endpoint was the need for additional uterotonic medication.MethodsEach of the five participating Dutch hospitals treated 50–100 term patients with 100 μg of intravenous carbetocin on prescription. Each centre retrieved charts of 250 patients treated with oxytocin according to the hospital’s policy for the prevention of uterine atony (oxytocin bolus 5 IU, bolus 10 IU or bolus 5 IU followed by 10 IU in 2 h).ResultsIn the carbetocin group 462 subjects were included and in the oxytocin group 1,122. The proportion of subjects needing additional uterotonic treatment was 3.1 % (95 % CI 1.7–5.1 %) after carbetocin and 7.2 % (5.8–8.9 %) after oxytocin; relative risk 0.41 (0.19–0.85); p = 0.0110. Carbetocin was most effective compared with the oxytocin 5 IU bolus subgroup with less need for additional uterotonic medication (3.1 vs. 9.3 %, p = 0.0067) and blood transfusions (2.2 vs. 3.6 %, p = 0.0357).ConclusionsCompared with oxytocin, prophylaxis of uterine atony with carbetocin after an elective CS diminished the need for additional uterotonics by more than 50 %.

Objective. To test the effect of 800 lg of misoprostol orally on the prevention of manual removal of retained placenta. Design. Multicenter, doubleblinded, placebo-controlled, randomized trial. Setting. One university and one non-university teaching hospital in the Netherlands. Sample. 99 women with retained placenta (longer than 60 min after childbirth) in the absence of postpartum hemorrhage. Methods. Eligible women were administered either 800 lg of misoprostol or placebo orally. Main outcome measures. Number of manual removals of retained placenta and amount of blood loss. Results. Manual removal of retained placenta was performed in 50% of the women who received misoprostol and in 55% who received placebo (relative risk 0.91, 95% confidence interval 0.62-1.34). No difference in the amount of blood loss (970 vs. 1120 mL; p = 0.34) was observed between the two groups. Conclusions. Administration of 800 lg of oral misoprostol, one hour after childbirth, does not seem to reduce the number of manual removals of retained placentas. The time elapsing results in the delivery of 50% of the retained placentas at the expense of an increased risk of postpartum hemorrhage.Abbreviations: PPH, postpartum hemorrhage.

We found that the prevalence of HBP carriers is high enough in our population to warrant HBP testing for the entire multiethnic population in early pregnancy at the time of anemia screening. This is feasible as most women had their booking early in their first trimester.