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) [2]. The model has been externally validated on 2899 PUL recruited between 2015 and 2017 at 8 teaching and district general hospitals in the UK [3].

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.

Please note - this guide on management advice is based on using the M6 model to triage women with PUL in the recent clinical implementation study [3]. This enabled effective triage with few misclassified ectopic pregnancies, of which none came to significant clinical harm or suffered a serious adverse clinical event. Although this is a guide for management, final management decision should take into account senior clinical review and current patient status.

* 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.

References

  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 2016;48:642-649. * Joint first authors.
  3. Christodoulou E, Bobdiwala S, Kyriacou C, Farren J, Mitchell-Jones N, Ayim F, Chohan B, Abughazza O, Guruwadahyarhalli B, Al-Memar M, Guha S, Vathanan V, Gould D, Stalder C, Wynants L, Timmerman D, Bourne T, Van Calster B. The M6 risk prediction model and two-step strategy to characterize pregnancies of unknown location: a multicentre external validation study. Submitted. Available as preprint.