In 2011, the first systematic review of the evidence behind the diagnostic criteria for miscarriage was published. It states, ‘‘findings were
limited by the small number and poor quality of the studies,’’ and concluded that further studies were, ‘‘urgently required before setting
future standards for the accurate diagnosis of early embryonic demise.’’ This implies that data used to define criteria to diagnose miscarriage
are unreliable. The 2011 Irish Health Service executive review into miscarriage misdiagnosis highlighted this issue. In parallel
to these publications a multicenter prospective study was published examining cut-off values for mean sac diameter (MSD) and embryo
size to define miscarriage. The authors also published evidence on expected findings when ultrasonography is repeated at an interval.
This led to guidance on diagnostic criteria for miscarriage in the UK changing. These new criteria state miscarriage be considered only
when: an empty gestation sac has an MSD ofR25 mm (with no obvious yolk sac), or embryonic crown rump lengthR7 mm (the latter
without evidence of fetal heart activity). If in doubt, repeating scans at an interval is emphasized. It is axiomatic that decisions about
embryonic viability must not be open to doubt. So it is surprising how little evidence exists to support previous guidance. Any clinician
working in this area knows of women being wrongly informed that their pregnancy has failed.
This cannot be acceptable and guidance in this area must be ‘‘failsafe.’’ (Fertil Steril 2012;98:
1091–6. 2012 by American Society for Reproductive Medicine.)
Key Words: Miscarriage, embryo, PUL, PUV, misdiagnosis, early pregnancy, vaginal ultrasound

CRITERIA USED TO DEFINE
A MISCARRIAGE WHEN
A GESTATION SAC WITH OR
WITHOUT A YOLK SAC OR
EMBRYO HAS BEEN
VISUALIZED IN THE UTERUS
The American College of Radiologists
(ACR) guidelines, updated in 2009 (1),
state, ‘‘The embryo will initially appear
as a thickened, linear echogenic structure
between the yolk sac and the gestational
sac, possibly seen at 8 mm sac
size, but definitely by 16mm,’’ and ‘‘embryonic
demise may be diagnosed with
an embryo >5 mm without cardiac activity.’’
This statement defines a miscarriage
therefore as an empty gestation
sac that measures more than 16 mm in
mean diameter. The guideline refers to
just two papers, one from 1988 based
on 35 patients with a mean gestation
sac diameter over 16mm(2) and another
from 1990 based on a total of 12 embryos
with crown rump length (CRL)
measurements between 4.0 and 4.9
mm (3). The entire database used by
the ACR to define the failure of a pregnancy
comprises just 47 patients. It
also defines normal gestation sac
growth as being one mm per day. There
is a paucity of data in relation to this
topic. A longitudinal study to examine
this was conducted by Nyberg and colleagues
on 30 pregnancies all of which
were abnormal (4). The authors were unable to define a growth rate that could definitively be associated
with subsequent pregnancy failure.
The ACR guideline also states when discussing pregnancies
of unknown location:
These patients may also be considered to have a pregnancy
of unknown location (PUL). In this situation, the
American Society of Reproductive Medicine (ASRM) advocates
uterine curettage to rule out an ectopic pregnancy
when the serum b- hCG level is over 2,400 mIU/
mL (1). This approach will undoubtedly result in the
loss of some early viable intrauterine pregnancies (1).
The risks associated with some criteria used to selectwomen
for curettage have been highlighted previously by Condous
et al. (5) who also raised concerns about the risk of inadvertent
termination associated with this management approach.
In another study, Goldstein and colleagues (6) concluded:
In our hands, the absence of cardiac activity in embryos
measuring 4mmor 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.

CRL measurement range by the second observer for a CRL measured
by the first observer.
CRL1 of first observer (mm)
95% PI for CRL1 of second
observer (mm)
5 4.5–5.6
6 5.4–6.7
7 6.3–7.9
10 8.9–11.2
20 17.9–22.4
30 26.7–33.5

MSD measurement range by the second observer for an MSD
measured by the first observer.
MSD of first observer (mm)
95% PI for MSD of second
observer (mm)
10 8.5–12.6
15 12.7–18.6
16 13.5–19.8
17 14.3–21.0
18 15.1–22.2
19 16.0–23.4
20 16.8–24.5
21 17.6–25.7
22 18.4–26.9
23 19.2–28.0
24 20.0–29.2
25 20.9–30.4
30 24.9–36.1
40 32.5–47.6

CONCLUSION
It is now almost twenty years since the landmark Cardiff enquiry
in the UK into the misdiagnosis of miscarriage that led
to a common sense report by Hately and colleagues (22) that
essentially emphasized the Hippocratic Oath, ‘‘to do no harm.’’
A version of this report, which was published in 1995 would
merit republication today, and should be compulsory reading
for all healthcare practitioners who work in the care of women
in early pregnancy. The authors were clear that errors in the
diagnosis of miscarriage ‘‘may happen in any busy ultrasound
practice unless proper protocols and precautions are established.’’
They advised caution and emphasized the need to repeat
scans at an interval to ensure no mistakes are made. In
2011 there was a public enquiry in Ireland into a number of
documented cases where miscarriage had been wrongly diagnosed
(23). How can we have a situation where the size of an
empty sac used to define a miscarriage ranges from an MSD of
15 mm to 25 mm, even in published guidelines, and with individual
clinicians probably not even adhering to this? It is inconceivable that criteria to pronounce death at any other
phase of human life could be as open to misinterpretation
as those that exist currently in early pregnancy. For the majority
of women who miscarry we have no treatment to offer
for what is a natural process, however we can certainly do
harm. To avoid misdiagnosis of pregnancy failure it is essential
to set conservative cut-off values on which to base a diagnosis
of miscarriage, and the amended RCOG guidance seems
the logical approach to this pending even larger prospective
studies being available.
Early pregnancy care is not just an issue for clinicians. Patient
expectationneeds to bemanaged aswell.Home pregnancy
tests are informing women they are pregnant even before they
have missed a period. If they attend for a scan too early it ismore
likely that they will have an inconclusive result and so be potentially
at risk of a diagnostic error. Bottomley et al. (9) has shown
how the likelihood of a pregnancy being classified as a PUL or
PUV is largely a reflection of gestational age. Patient groups
have a role to play by educating women that a result is not always
possible on the basis of one scan or blood test, and that
early scans may well in be inconclusive.
The management of miscarriage has also changed. In
many developed countries, the majority are probably now
managed conservatively without the need for surgery as evidence
has shown equivalent low complication rates for expectant,
medical and surgical treatments, with good success
rates for all three approaches (24). Waiting a few days in order
to make a definitive diagnosis is highly unlikely to lead to
physical harm. Undoubtedly the anxiety associated with being
uncertain about the status of a pregnancy is very significant,
although we now have indicators that can help us
counsel women about what will be the likely outcome
at the time of a repeat examination (9, 25). The question
of viability and potential harm associated with
inappropriate management of PUL is covered elsewhere in
this issue of the journal. However inadvertent termination
of a potentially viable wanted pregnancy is surely the worst
possible outcome for any woman. Diagnosing viability in
early pregnancy matters, as a single mistake is one too
many for any couple looking forward to their pregnancy.
For us, the key phrase in the Cardiff report is, ‘‘the death of
an early pregnancy should be regarded as of equal
significance to that occurring at a later stage’’ (22). This
sentence should be printed on the ultrasound machine in
any unit that examines women in early pregnancy.