Predicting the likelihood of successful medical treatment of early pregnancy loss:development and internal validation of a clinical prediction model

STUDY QUESTION: What are clinical predictors for successful medical treatment in case of early pregnancy loss (EPL)? SUMMARY ANSWER: Use of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start are predictors for successful medical treatment in case of EPL. WHAT IS KNOWN ALREADY: Success rates of medical treatment for EPL vary strongly, between but also within different treatment regimens. Up until now, although some predictors have been identified, no clinical prediction model has been developed yet. STUDY DESIGN, SIZE, DURATION: Secondary analysis of a multicentre randomized controlled trial in 17 Dutch hospitals, executed between 28 June 2018 and 8 January 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with a non-viable pregnancy between 6 and 14 weeks of gestational age, who opted for medical treatment after a minimum of 1 week of unsuccessful expectant management. Potential predictors for successful medical treatment of EPL were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques. MAIN RESULTS AND THE ROLE OF CHANCE: 237 out of 344 women had a successful medical EPL treatment (68.9%). The model includes the following variables: use of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start. The model shows a moderate capacity to discriminate between success and failure of treatment, with an AUC of 67.6% (95% CI = 64.9-70.3%). The model had a good fit comparing predicted to observed probabilities of success but might underestimate treatment success in women with a predicted probability of success of ∼70%. LIMITATIONS, REASONS FOR CAUTION: The vast majority (90.4%) of women were Caucasian, potentially leading to less optimal model performance in a non-Caucasian population. Limitations of our model are that we have not yet been able to externally validate its performance and clinical impact, and the moderate accuracy of the prediction model of 0.67. WIDER IMPLICATIONS OF THE FINDINGS: We developed a prediction model, aimed to improve and personalize counselling for medical treatment of EPL by providing a woman with her individual chance of complete evacuation. STUDY FUNDING/COMPETING INTEREST(S): The Triple M Trial, upon which this secondary analysis was performed, was funded by the Healthcare Insurers Innovation Foundation (project number 3080 B15-191). TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT03212352

Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding

Acknowledgments: We thank all the women who participated in this trial; the participating general practitioners, gynecologists, and hospitals; the research nurses; and the staff of the Dutch Consortium for Studies in Women’s Health and Reproduction.Peer reviewedPublisher PD

A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population

The predictive value of medical history taking and Chlamydia IgG ELISA antibody testing (CAT) in the selection of subfertile women for diagnostic laparoscopy: a clinical prediction model approach

BACKGROUND: Medical history taking as well as Chlamydia antibody titre (CAT) testing are currently used in the selection of patients for diagnostic laparoscopy with tubal patency testing. Most research has focused on the predictive value of CAT in isolation from medical history. We assessed therefore whether the combination of medical history and CAT improves the efficiency of selecting patients for laparoscopy as compared to the use of either medical history or CAT. METHODS: Data of 207 consecutive subfertile women were used to create multivariable logistic regression models for the prediction of tubal disease as diagnosed by diagnostic laparoscopy. RESULTS: The model with data of medical history only had an area under the receiver operating characteristic curve (AUC) of 0.65 (95% CI 0.56-0.74). Addition of CAT increased the AUC to 0.70 (95% CI 0.62-0.78) (P = 0.065). CAT was positive in 40 women and showed a sensitivity of 0.37 (95% CI 0.26-0.49) for a specificity of 0.88 (95% CI 0.82-0.93). In CAT positive women, a blank medical history did not decrease the probability of tubal disease. Of the 167 women tested CAT negative, 23 (14%) still had a high probability of disease due to their medical history and 11 of them (48%) showed tubal abnormalities on diagnostic laparoscopy. CONCLUSIONS: CAT testing adds valuable information to a woman's risk profile based on her medical history. The combination of medical history taking and CAT testing has a better yield for diagnosing tubal disease than either of these alon

Evaluating prediction models in reproductive medicine

Prediction models are used in reproductive medicine to calculate the probability of pregnancy without treatment, as well as the probability of pregnancy after ovulation induction, intrauterine insemination or in vitro fertilization. The performance of such prediction models is often evaluated with a receiver operating characteristic (ROC) curve. The area under the ROC curve, also known as c-statistic, is then used as a measure of model performance. The value of this c-statistic is low for most prediction models in reproductive medicine. Here, we demonstrate that low values of the c-statistic are to be expected in these prediction models, but we also show that this does not imply that these models are of limited use in clinical practice. The calibration of the model (the correspondence between model-based probabilities and observed pregnancy rates) as well as the availability of a clinically useful distribution of probabilities and the ability to correctly identify the appropriate form of management are more meaningful concepts for model evaluatio

Atypical endometrial polyps and the incidence of endometrial cancer: a retrospective cohort study

Objective The aim of this study was to evaluate the incidence of endometrial carcinoma, proven after hysterectomy, in patients diagnosed with atypical endometrial hyperplasia confined to a polyp. A secondary aim was to establish factors associated with (pre-)malignant alterations in a polyp. Design A retrospective cohort study. Setting Maastricht University Medical Centre (MUMC+) and Maxima Medical Centre in Eindhoven/Veldhoven (Maxima MC). Population Women who underwent a hysteroscopic polyp resection between 2008 and 2016. Methods Patient characteristics and histopathology results of the polyp and, in the case of a hysterectomy, uterus were collected from patients' charts. Results A total of 1445 complete hysteroscopic polyp resections were included. Of those, 1390 polyps showed benign histopathology results, 39 polyps contained atypical hyperplasia and 16 polyps contained endometrial carcinoma. A hysterectomy was performed in 35 women who were diagnosed with atypical hyperplasia confined to a polyp after hysteroscopic polyp resection. Histopathological assessment showed no additional (pre-)malignant changes of the endometrium in 12 women (30.8%), atypical hyperplasia in 11 women (28.2%) and endometrial carcinoma in 12 women (30.8%). None of the prognostic factors under consideration were significantly associated with (pre-)malignant changes in a polyp. Conclusion The incidence of endometrial carcinoma in the surrounding endometrium after complete resection of a polyp with atypical hyperplasia is 30.8% in this study. This supports the current advice to perform a hysterectomy and bilateral salpingo-oophorectomy. No prognostic factor for (pre-)malignant changes in a polyp was established. Tweetable abstract The incidence of endometrial carcinoma after complete resection of a polyp with atypical hyperplasia is high

Atypical endometrial polyps and the incidence of endometrial cancer:a retrospective cohort study

Objective The aim of this study was to evaluate the incidence of endometrial carcinoma, proven after hysterectomy, in patients diagnosed with atypical endometrial hyperplasia confined to a polyp. A secondary aim was to establish factors associated with (pre-)malignant alterations in a polyp. Design A retrospective cohort study. Setting Maastricht University Medical Centre (MUMC+) and Maxima Medical Centre in Eindhoven/Veldhoven (Maxima MC). Population Women who underwent a hysteroscopic polyp resection between 2008 and 2016. Methods Patient characteristics and histopathology results of the polyp and, in the case of a hysterectomy, uterus were collected from patients' charts. Results A total of 1445 complete hysteroscopic polyp resections were included. Of those, 1390 polyps showed benign histopathology results, 39 polyps contained atypical hyperplasia and 16 polyps contained endometrial carcinoma. A hysterectomy was performed in 35 women who were diagnosed with atypical hyperplasia confined to a polyp after hysteroscopic polyp resection. Histopathological assessment showed no additional (pre-)malignant changes of the endometrium in 12 women (30.8%), atypical hyperplasia in 11 women (28.2%) and endometrial carcinoma in 12 women (30.8%). None of the prognostic factors under consideration were significantly associated with (pre-)malignant changes in a polyp. Conclusion The incidence of endometrial carcinoma in the surrounding endometrium after complete resection of a polyp with atypical hyperplasia is 30.8% in this study. This supports the current advice to perform a hysterectomy and bilateral salpingo-oophorectomy. No prognostic factor for (pre-)malignant changes in a polyp was established. Tweetable abstract The incidence of endometrial carcinoma after complete resection of a polyp with atypical hyperplasia is high