Why greater emphasis must be given to getting the diagnosis right: the example of miscarriage

In 2011, the editor of the journal Ultrasound in Obstetrics and Gynecology commissioned a systematic review showing there was a worrying lack of data from which to derive safe guidelines for the diagnosis of miscarriage and highlighted the need for larger prospective studies. Systematic reviews have a habit of concluding that evidence is substandard and nothing can be done pending the perfect study. However, on this occasion, the conclusions were correct and it was clear that at that time the guidelines being used to diagnose miscarriage were too open to interpretation, based on inadequate data and failed to account for both inter-observer variation and the quality of ultrasonography. For me the issue came to a head when I was chairing an early pregnancy session at the International Society for Ultrasound in Obstetrics and Gynecology meeting in Prague in 2010. I asked the audience what they used as a cut-off value for mean gestation sac diameter (MSD) to define miscarriage, and the answers ranged from a very worrying 2 to a more reassuring 20 mm. When talking to colleagues there was a sense of concern that the criteria used to diagnose miscarriage were less than watertight. From a patient’s perspective if there is one decision a women would expect clinicians to get right with absolute certainty, it would be whether their baby is alive or not. This prompted us to review the evidence behind the guidelines used to make these decisions. We first turned to the American College of Radiologists (ACR) guideline, updated in 2009, that stated that ‘embryonic demise may be diagnosed with an embryo >5 mm without cardiac activity’. Miscarriage was also defined as an empty gestation sac measuring ≥16 mm in mean diameter. The guideline referred to two papers, one from 1988 based on 35 pregnancies with an MSD >6 mm and another from 1990 based on just 12 embryos with crown rump length (CRL) measurements between 4.0 and 4.9 mm. A further paragraph in the ACR guideline at that time in relation to pregnancy of unknown location (PUL) read: ‘These patients may also be considered to have a PUL. In this situation, the American Society of Reproductive Medicine (ASRM) advocates uterine curettage to rule out an ectopic pregnancy when the serum bhCG level is >2400 mIU/mL. This approach will undoubtedly result in the loss of some early viable intrauterine pregnancies’. This remarkable statement highlighted the lack of rigour associated with early pregnancy care at that time. These criteria being used to select women for curettage in this context had been highlighted previously by Condous et al., who raised concerns about the risk of inadvertent termination associated with this management approach. In another study on miscarriage, Goldstein concluded, ‘in our hands, the absence of cardiac activity in embryos measuring 4 mm or more is reliably associated with embryonic death. In contrast, the lack of cardiac activity in embryos of 3 mm or less is non-diagnostic and may warrant follow-up study in 3–5 days’. This was certainly a definitive statement, but one based on just 22 patients. Assessing early pregnancy viability was the subject of a review published in the American Family Physician in 2009. This suggested an anembryonic pregnancy could be defined as the ‘presence of a gestational sac larger than 18 mm without evidence of embryonic tissues (yolk sac or embryo)’. This statement was considered to be of grade C evidence according to the SORT criteria, i.e. based on opinion and with limited evidence. The question therefore remained: for an empty gestation sac what MSD measurement should be associated with uncertain viability? One of the few prospective studies on the subject available at that time was from Elson et al. They examined 200 pregnancies with an empty gestation sac with an MSD <20 mm and found considerable overlap between the MSD of viable and non-viable pregnancies. They observed two pregnancies with an empty sac with an MSD between 18 and 20 mm that were subsequently shown to be viable. As the authors pointed out: ‘ultrasound is an operator-dependent method and it is conceivable that an inexperienced operator may fail to detect an embryo in a relatively large sac due to a poor examination technique’. This study was limited to pregnancies with an MSD ≤20 mm, but it rang alarm bells for those believing a cut-off value for MSD of 20 mm had a large margin of error. Bearing in mind the United States guidelines used a MSD cut-off value of ≥16 mm, the paper by Rowling et al. in Radiology is also relevant. In this retrospective study based on case reviews, five of 59 (8%) patients with no embryo visible and an MSD of 16 mm were subsequently recognised as viable pregnancies. *Correspondence to email tbourne@ic.ac.uk doi: 10.1002/ajum.12004