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

Abstract

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.

Keywords: early pregnancy loss; mifepristone; misoprostol; personalized medicine; prediction model.

Figure 1.

Trial profile. = included in intention-to-treat analysis. = excluded from intention-to-treat analysis.

Figure 2.

Receiver operating characteristic curve of the prediction model. Area under the curve = 67.6% (95% CI = 64.9–70.3%), indicating reasonable discriminative performance.

Figure 3.

Predicted and observed probabilities of successful treatment per group of 215 predictions. Each group represents a range of 12.5% of all predicted probabilities (i.e. Group 1 lowest 12.5% of probabilities, Group 8 highest 12.5% of probabilities).

Figure 4.

Calibration curve of prediction model for successful medical treatment of early pregnancy loss. Points show predicted and observed success rates for the eight groups shown in Fig. 3.

Figure 5.

A nomogram for prediction of the chance of successful medical treatment in case of early pregnancy loss. Each factor (BMI, symptoms, mifepristone, prior curettages) has a score on the point scale, which can be determined by drawing a vertical line from the factor scale to the point scale. The estimated chance of success is calculated by adding all points to generate a point total, locating this score on the total point scale and subsequently the corresponding chance of success.