Welcome to the webpage for the M6 risk model to characterize pregnancies of unknown location (PUL*)

The M6 risk model can be used by clinicians to characterize pregnancies of unknown location. The model was based on women with a PUL who had a serum hCG level on presentation >25 IU/L. M6 predicts the probability that the PUL is a failed pregnancy, an intra-uterine pregnancy (IUP), or an ectopic pregnancy (including persisting PUL). For terminology please see Barnhart et al (2011) [1]. The M6 model uses the following markers: initial hCG level (IU/L), hCG ratio over a 48 hour period (hCG at 48hr / initial hCG), and initial progesterone level (nmol/L). The last predictor is optional, although its inclusion improves model performance. If the patient is taking progesterone supplements, the progesterone level is unreliable and hence should not be used.

M6 was developed by clinicians and statisticians from Imperial College London and KU Leuven, and was based on 2753 PUL from two London-based university teaching hospitals (St. George’s Hospital and Queen Charlotte’s and Chelsea Hospital). The manuscript describing the model is published in Ultrasound in Obstetrics and Gynecology, and we append the abstract of the paper below [2].

M6 is part of a two-step triage protocol to identify patients at high risk of ectopic pregnancy.2 The first step triages patients after the first visit using initial progesterone: if the level is ≤2 nmol/L the patient is classified as low risk – Failed, if the level is >2 nmol/L the patient is scheduled to come back after around 48 hours to have a second hCG measurement (second step). Then M6 is applied, and if the predicted risk of being EP is at least 5% the patient is classified as high risk. If the risk of being EP is <5% then the patient is classified as low risk – Failed pregnanacy or as low risk – IUP depending on which predicted risk is highest. See Figure 1 for a schematic overview. The M6 model can also be used in isolation, i.e. without the first step triage.

* For the purposes of the research data we have used to develop this model, a PUL has been defined as: Pregnancy of unknown location (PUL) describes a woman who has a positive pregnancy test without evidence of a pregnancy inside or outside the endometrial cavity using transvaginal sonography (TVS) [2].

The M6 model is implemented electronically in various formats:

  1. App for Android
  2. App for iPhone
  3. Web application
  4. Protected excel sheet

Figure 1. Two-step triage protocol, including suggested management.
Figure explaining the two-step triage protocol, including suggested management.

Abstract of the M6 paper [2]


A uniform rationalized management protocol for pregnancies of unknown location (PUL) is lacking. We developed a two-step triage protocol based on presenting serum progesterone (step 1) and hCG ratio two days later (step 2) to select PUL at high-risk of ectopic pregnancy (EP).


Cohort study of 2753 PUL (301 EP), involving a secondary analysis of prospectively and consecutively collected PUL at two London-based university teaching hospitals. Using a chronological split we used 1449 PUL for development and 1304 for validation. We aimed to select PUL as low-risk with high confidence (high negative predictive value, NPV) while classifying most EP as high-risk (high sensitivity). The first triage step selects low-risk PUL at presentation using a serum progesterone threshold. The remaining PUL are triaged using a novel logistic regression risk model based on hCG ratio and initial serum progesterone (second step), defining low-risk as an estimated EP risk <5%.


On validation, initial serum progesterone ≤2nmol/l (step 1) selected 16.1% PUL as low-risk. Second step classification with the risk model M6P selected an additional 46.0% of all PUL as low-risk. Overall, the two-step protocol classified 62.1% of PUL as low-risk, with an NPV of 98.6% and a sensitivity of 92.0%. When the risk model was used in isolation (i.e. without the first step), 60.5% of PUL were classified as low-risk with 99.1% NPV and 94.9% sensitivity.


The two-step protocol can efficiently classify PUL into being at high or low risk of complications.


  1. Barnhart K, van Mello NM, Bourne T, Kirk E, Van Calster B, Bottomley C, Chung K, Condous G, Goldstein S, Hajenius PJ, Mol BW, Molinaro T, O’Flynn O’Brien KL, Husicka R, Sammel M, Timmerman D. Pregnancy of unknown location: a consensus statement of nomenclature, definitions, and outcome. Fertility & Sterility 2011;95:857-866.
  2. Van Calster B*, Bobdiwala S*, Guha S, Van Hoorde K, Al-Memar M, Harvey R, Farren J, Kirk E, Condous G, Sur S, Stalder C, Timmerman D, Bourne T. Managing pregnancy of unknown location based on initial serum progesterone and serial serum hCG: development and validation of a two-step triage protocol. Ultrasound in Obstetrics and Gynecology, in press. * Joint first authors.