The Role Ultrasound in Early Pregnancy

PRECONGRESS COURSE 02
The role of ultrasound

in early pregnancy
Special Interest Group Implantation
and Early Pregnancy
Geneva Switzerland, 2 July 2017
2
Theroleofultrasoundinearlypregnancy
Geneva,Switzerland
2July2017
Organisedby
theSpecialInterestGroupImplantationandEarlyPregnancy
Contents
Coursecoordination,coursetype,coursedescription,targetaudience,
educationalneedsandexpectedoutcomes Page3
Programme Page4
Speakerscontributions
Introductiontoearlypregnancyultrasound
EmmaKirk,UnitedKingdom Page5
Thenormalearlyintrauterinepregnancy411weeks
PetyaChaveeva,Bulgaria Page 16
Diagnosingmiscarriage
CeciliaBottomley,UnitedKingdom Page 28
Pregnancyofunknownlocation
TomBourne,UnitedKingdom Page 60
Ectopicpregnancy
EmmaKirk,UnitedKingdom Page 87
Theadnexaandotherpathology
WouterFroyman,Belgium Page 107
Earlydetectionofcongenitalandchromosomalabnormalities
PetyaChaveeva,Bulgaria Page 136
Breakingbadnews
Rachel Small, United Kingdom Page 148
Notes Page 159
Page 2 of 166
Coursecoordination
SiobhanQuenby(UnitedKingdom)andEmmaKirk(UnitedKingdom)
Coursetype
Basicandadvanced
Coursedescription
Thiscoursewillinvolvetheoreticaltrainingonultrasoundinearlypregnancy.
Targetaudience
SeniorandJuniordoctorsandnurseswhowanttolearnmoreaboutultrasonsographyinpractice
fromthosewhoneverscannedtoexperiencedultrasonographerswhowanttogetbetter.
Educationalneedsandexpectedoutcomes
TheearlypregnancyCSGyoungermembershavediscussedthisideawithjuniordoctorsinseveral
Europeancountries,UK,Netherlands,Denmarkandagreedtherewasagreatneedforthiscoursein
Europe.
Page 3 of 166
Scientificprogramme
Chairmen: SiobhanQuenby,UnitedKingdom
EmmaKirk,UnitedKingdom
09:0009:25 Introductiontoearlypregnancyultrasound
09:2509:30 Discussion
09:3009:55 Thenormalearlyintrauterinepregnancy411weeks
PetyaChaveeva,Bulgaria
10:0010:25 Diagnosingmiscarriage
CeciliaBottomley,UnitedKingdom
10:3011:00 Coffeebreak
Chairmen: PetyaChaveeva,Bulgaria
MerelvandenBerg,TheNetherlands
11:0011:25 Pregnancyofunknownlocation
TomBourne,UnitedKingdom
12:0012:25 Ectopicpregnancy
12:3013:30 Lunchbreak
Chairmen: EmmaKirk,UnitedKingdom
CeciliaBottomley,UnitedKingdom
13:3014:00 Theadnexaandotherpathology
WouterFroyman,Belgium
14:1514:45 Earlydetectionofcongenitalandchromosomalabnormalities
PetyaChaveeva,Bulgaria
15:0015:30 Coffeebreak
Chairmen: SiobhanQuenby,UnitedKingdom
MerelvandenBerg,TheNetherlands
15:3017:00 Workshops
15:3016:00CaseexamplesAllspeakers,leadbyEmmaKirk
16:0016:30DiagnosticdilemmasAllspeakers,leadbyCeciliaBottomley
16:3017:00BreakingbadnewsRachelSmall,UnitedKingdom
Page 4 of 166
IntroductiontoEarly
PregnancyUltrasound
EmmaKirk
MRCOGMD
Conflict of Interest
None
Page 5 of 166
Objectives
To understand:
Indicationsforultrasoundassessmentin
earlypregnancy
Safetyinearlypregnancy
TransvaginalversesTransabdominal
Ultrasound
Systematicapproachtoexamination
Use of USS in Early Pregnancy
In UK only 2 routine USS examinations at

12 and 20 weeks gestation
USS prior to this has become central to the

management of early pregnancy problems
Early USS are indicated in women after

assisted conception or those thought to be
at increased risk of an early pregnancy
complication
Page 6 of 166
Aims of the Early Pregnancy USS
Presence of an intrauterine
pregnancy
Establish viability
Determine number of embryos
Determine gestational age
Reassure about absence of

complications
Positive Pregnancy Test
TVS
70-90% 10-30%
Diagnostic Non-diagnostic
Intra-Uterine Ectopic Pregnancy Pregnancy of

Pregnancy (IUP) (EP) Unknown Location
Failing IUP EP Persistent

PUL PUL
Page 7 of 166
Setting for the USS
In the UK majority are carried out in

specialist Early Pregnancy Assessment Units
Specialist Units:
RCOG requirement
Separate to a routine antenatal clinic
Immediate access to USS facilities
Safety of Early Pregnancy USS
Evidence so far suggests that USS used in

standard pre-sets for clinical reasons during
embryonic development (conception to 10
weeks) is safe and benefits outweigh risks
Use the lowest output power

and the shortest scan time
consistent with acquiring the
required diagnostic information
ALARA principle as low as reasonably achievable
Page 8 of 166
Safety Indices
Ultrasound exposes developing embryo to

both mechanical and thermal stress.
Explanation RecommendedLevels*
MechanicalIndex MI MIisanonscreenindicatoroftherelativepotentialforultrasound AnMIof<1.0indicatesthateffects

toinduceanadversebioeffectbyanonthermalormechanical arisingfromacousticcavitationare
mechanism.Thisincludescavitation whichreferstothe veryunlikely.Ideallyaimforlevels<
0.7inearlypregnancyscanning.
developmentofgasbubblesinanacousticfieldathighnegative
pressuresandstreamingwhichistheexpansionandcontraction,or
collapse,ofgasbubblesduringtheoscillatorycycle.
ThermalIndex TI TIprovidesanindicationoftherelativepotentialforariseintissue ThehighertheTI,theshorterthe

temperature.Itisintendedtogivearoughguidetothelikelymaximum ultrasoundexposureshouldbe.TIS<
temperaturerisethatmightbeproducedafterlongexposure.Thereare 0.7 norestrictiononscantime.
3types: TIS0.71.0 restrictscantimeto<60
mins.
TISthermalindexforsofttissue.Theindexusedduringscanning<10
TIS1.01.5 restrictscantimeto<30
weeksofgestation.
mins.
TIB thermalindexforbone.
TIS>3.0 scanningnot
TIC thermalindexforcranialbone. recommended.
Scanning Modes
B-mode is safe in early pregnancy
Color Doppler and pulsed wave Doppler

involve greater average intensity and power
outputs as shown by higher TIS levels
Color Doppler therefore not recommended
for routine use
M-mode can be used to insonate fetal heart
3D safe, as often leads to shorter scan

times, but not to be used routinely
Page 9 of 166
Scanning Routes
Advantages Disadvantages
Transvaginal
(TVS) Higherfrequencies(upto7.5MHz) Depthofpenetrationislimiteddueto
Superiorresolutionofimages highfrequencyoftheultrasound
Requiresanemptybladder,sooften Lackofprobemobility.
morecomfortable.
Theprobecanbeusedtotouchthe
pelvicorganstotestforpain.
Thepelvicorganscanbemoved
withtheprobetoseeiftheyslide
easily.
Theprobecanbemovedinandout
ofthevaginatoadjustthedepthof
theorgansonthescreen.
Allowsbetterimaginginobese
patients.
Transabdominal
(TAS) Mayallowbettervisualisationof Decreasedresolution.
pregnanciesinalargefibroiduterus.
Oftenrequiresafullbladder.
Poorviewsinobesepatients.
Ultrasound Technique
Imageorientation:
Imageoptimisation:
Depth
Magnification
Focus
Gain
Page 10 of 166
Systematic Approach
Longitudinal View of the Uterus
Systematic Approach
Transverse View of the Uterus
Page 11 of 166
Systematic Approach
Visualisation of the Gestational Sac
Systematic Approach
Assessment of Embryonic Structures
Page 12 of 166
Systematic Approach
Visualisation of the Right Ovary
Systematic Approach
Visualisation of the Left Ovary
Page 13 of 166
Systematic Approach
Assessment of the Adnexa
Systematic Approach
Inspection of the Pouch of Douglas
Page 14 of 166
Systematic Approach
Inspection of the Pouch of Douglas
Other sites
Summary
An early pregnancy scan aims to confirm
pregnancy location, establish viability, determine
number of embryos and determine gestational
age
Ultrasound used in standard presets for clinical
reasons < 10 weeks is safe
A transvaginal ultrasound has a number of
advantages over a transabdominal scan in early
pregnancy
It is essential to provide a structured written report
Page 15 of 166
The Fetal Medicine Precongress Course
Foundation
The role of ultrasound in Early Pregnancy
The normal early intrauterine pregnancy 4-11 weeks
Petya Chaveeva
Consultant in Fetal Medicine
Ob/Gyn Shterev Hospital, Sofia, Bulgaria
The Fetal Medicine

Foundation Disclosure
I have no conflict of interest
Page 16 of 166
The Fetal Medicine
Foundation
Learning Objectives
Ultrasound assessment in early pregnancy
Normal appearance of gestational sac (GS), yolk sac

(YS), embryo
Assessment of multiple pregnancy, number of
embryos, chorionicity
Assessment of gestational sac diameter(GSD), crown
rump length (CRL)
The Fetal Medicine

Foundation
Ultrasound assessment in early pregnancy
Transvaginal Transabdominal
Gestational sac 4-5 wks 5-6 wks

Yolk sac 5-6 wks 6-7 wks
Embryo 5-6 wks 6-7 wks
FHB 5-6 wks 6-7 wks
Page 17 of 166
The Fetal Medicine
Foundation
Gestational sac
Visible at around 4 weeks of gestation

Assessment by transvaginal (TV) or transabdominal (TA)
ultrasound scan
Round fluid full collection in the uterine cavity
Growth in early pregnancy 1 mm/day
Surrounded by hyperechogenic rim
The Fetal Medicine

Foundation
Amnion
Visible at around 5 weeks of gestation

Membranous structure contains clear fluid
ultrasound scan
Separate the embryo and amniotic space from the
chorionic cavity
Obliterates the chorionic cavity by 13-16 weeks
Page 18 of 166
The Fetal Medicine
Foundation
Yolk sac
Visible at around 55.5 weeks of gestation, but not

visible after the first trimester
ultrasound scan
Round structure with hyperechogenic rim
Diameter at 6 mm at 10 weeks, then decreases
The Fetal Medicine

Foundation
Assess the heartbeat with M mode
Heartbeat visible from CRL >2-4 mm

Use M- mode on a frozen image
110bpm at 6 wks to 175 bpm at 9wks
Schats R, Jansen CAM, Wladimiroff WT: Embryonic heart activity: appearance and development in early
human pregnancy. Br J Obstet Gynaecol 1990;97:989994.
Page 19 of 166
The Fetal Medicine
Foundation Assess the viability
Length of embryo is around 1-2 mm when is visible for the first

time
Raise with 1mm per day
Cranial and caudal end of embryo is detectable when length is at

least 12 mm
In doubt about viability scan in a weeks time
Term viability is used for visible heart beating
In normal pregnancy embryos heart beats are visible at 37th day of

pregnancy and embryo length 2 mm, when heart tube starts
beating
In around 5-10% of pregnancies with embryo length between 2-4

mm heart beating are not visible, but this is not sign of missing
viability
The Fetal Medicine

Multiple pregnancy
Foundation
Zygocity & Chorionicity
Cleavage
Days 1-3
Morula
Days 4-8
Blastocyst
Days 9-12
Implanted
blastocyst
Days >12
Embyonic
disk formed
Page 20 of 166
The Fetal Medicine
Multiple pregnancy
Foundation
Chorionicity and zygocity
9 twins
2/3 1/3
6 Dizygotic 3 Monozygotic
All 1/3 2/3
7 Dichorionic 2 Monochorionic
All monochorionic twins are monozygotic

6 of 7 dichorionic twins are dizygotic
The Fetal Medicine

Foundation
Multiple pregnancy
Number of yolk sacs usually = Number of amnions
Page 21 of 166
The Fetal Medicine
Foundation
How to assess the chorionicity
Dichorionic : 2 chorions and 2 amnions

Monochorionic: 2 amnions
Ultrasound transducer at the right angles to the
membrane
Look for Lambda sign & T sign
The Fetal Medicine

Foundation
Twin pregnancy with vanishing twin

Prevalence at about 15%
Marton V, zadori J, Kozinszky Z, KereszturiA: Prevalences and pregnancy outcome of vanishing twin pregnancies
achieved by in vitro fertilization versus natural conception. Fertil Steril. 2016 Nov;106(6):1399-1406.
Page 22 of 166
The Fetal Medicine
Foundation
Multiple pregnancy
TRAP sequence
The Fetal Medicine

Intrafetal laser
Foundation
TRAP sequence
Method N Intrafetal laser

Cord coil 3 Jolly 2001 2
Cord ligation 40 Soothill 2002 2
Cord laser coagulation 59 Sepulveda 2004 1
Cord MP coagulation 6 Weisz 2004 2
ODonoghue 2008 10
Cord bipolar coagulation 86
Scheier 2012 6
Laser placental anastomoses 25 Wegrzyn 2012 1
Intrafetal alcohol 22 Berg 2013 11
Intrafetal MP coagulation 13 Novak 2013 1
Pagani 2013 16
Intrafetal laser coagulation 104
Chaveeva 2014 52
Intrafetal radiofrequency 108 Overall 104
0 10 20 30 40 50 60 70 80 90 100 0 10 20 30 40 50 60 70 80 90 100
Survival rate with 95% CI (%) Survival rate with 95% CI (%)
Chaveeva P, Poon LC, Sotiriadis A, Kosinski P, Nicolaides KH. Optimal method and timing of intrauterine intervention in twin
reversed arterial perfusion sequence: case study and meta-analysis. Fetal Diagn Ther 2014;35:267-79.
Page 23 of 166
The Fetal Medicine Fetal therapy
Foundation
Coelocentesis
Needle
Amniotic cavity
F
Celomic cavity
Trophoblast
Jurkovic D, Jauniaux E, Campbell S, Pandya P, Cardy D, Nicolaides KH. Coelocentesis: a new technique for early
prenatal diagnosis. Lancet 1993; 341:1623-4.
Giambona A, Damiani G, Leto F, Jakil C, Renda D, Cigna V, Schillaci G, Picciotto F, Nicolaides KH, Passarello C, Makrydimas
G, Maggio A. Embryo-fetal erythroid cell selection from celomic fluid allows earlier antenatal diagnosis of hemoglobinopathies.
Prenat Diagn 2016 Feb 18. doi: 10.1002/pd.4793.
The Fetal Medicine

Foundation
Early pregnancy biometry
Study population: 4, 698 singleton pregnancies
Page 24 of 166
The Fetal Medicine
Foundation
Embryonic or fetal crown-rump length (CRL)
At less than 7 weeks of gestation the CRL is

measured by the greatest length of the embryo
From 7 weeks of gestation the CRL is measured in
the sagittal section of the embryo
Papaioannou et al., 2010
The Fetal Medicine

Foundation
Gestational sac diameter (GSD)
3 perpendicular diameters with the calipers

placed at the inner edges of the trophoblast
Page 25 of 166
The Fetal Medicine
Foundation
Measurement of Yolk sac
3 perpendicular diameters with the calipers

placed at the center of the yolk sac wall
The Fetal Medicine

Foundation Normal intrauterine pregnancy
Page 26 of 166
The Fetal Medicine
Foundation In Summary
Normal intrauterine pregnancy 4-11 weeks
Aware of normal appearance and assessment of GS, YS, FHB,

Embryo
Diagnosis of multiple pregnancy and determine chorionicity
Date the pregnancy according to the CRL measurment
Fetal interventions in early pregnancy can take place
Thank you
Page 27 of 166
DIAGNOSIS OF MISCARRIAGE
ESHRE PRE-CONGRESS COURSE
2017
Cecilia Bottomley MRCOG MD

Chelsea and Westminster Hospital
London
Declaration
Advisory Board Clearblue

Advisory Board Alliance Pharma
Page 28 of 166
Learning Objectives
To:
Understand the role of ultrasound in the diagnosis of miscarriage
Develop knowledge of the evidence base for ultrasound diagnosis of
miscarriage
Learn the diagnostic criteria for safe diagnosis of miscarriage
Learn about prediction of miscarriage using ultrasound soft markers
Explore some diagnostic dilemmas in the diagnosis of miscarriage
Miscarriage Definition
Spontaneous loss of pregnancy before the embryo/fetus
reaches viability
(Includes all pregnancy losses from the time of conception

until 24 weeks of gestation*, but if the baby shows signs of
life then it is classified as a neonatal death)
Majority <12/40
Incidence decreases with gestation
3% at end of first trimester
*22/40 in some countries
Page 29 of 166
Miscarriage
Most common serious pregnancy complication

Low physical morbidity or mortality
Social and psychological impact
Breaking bad news

Accurate and certain diagnosis
Avoid termination of potentially viable pregnancy
Avoid false reassurance when likely to be nonviable
What really matters to the clinician?
He/she
does not want to miss an ectopic pregnancy
does not want to terminate a potentially viable pregnancy
needs to communicate consistent & appropriate information

to the woman
needs to arrange a rational & appropriate management plan

and follow up
Page 30 of 166
Clinical examination vs USS
50% misdiagnosis on
clinical examination
alone
Stable woman
USS primary diagnostic
tool
Unstable
Speculum for open cervix,
products in os
WieringadeWaard etal.2002
Well accepted by patients

TVS u
u Full bladder not required

u Least invasive method
u Relatively cheap with few complications
u Operator dependant
Page 31 of 166
Ultrasounddiagnosisofmiscarriage
Completemiscarriage
Incompletemiscarriage
Missedmiscarriage
Inhomogenous echoeswithin Nonviableintrauterine
Emptyuterus
theendometrialcavity gestationsac
Previouslyvisualised
Meansacdiameter>25mm
intrauterinepregnancy
withnoembryo
Or
Embryogreaterthan7mm
withnocardiacactivity
Or
Sacdiameter<25mmor
embryo<7mmbutnochange
after714d
TerminologyforEarlyPregnancyEvents
AdaptedfromFarquharson2005andRCOG2006
Biochemicalpregnancyloss Historyofpositivepregnancytestfollowedby
negativetest,withoutanultrasound assessment
havingbeenperformed
Empty sac Gestationsacwithabsentembryonicstructures
Fetalloss Previousidentificationofembryoorfetusand heart
activityfollowedbylossofheartactivity
EarlyPregnancyloss/Delayedmiscarriage/ Intrauterinepregnancywithevidenceoflostfetal
Missedmiscarriage heartactivityand/orfailureofCRLtoincreaseover
oneweek
Or
Persisting presenceofemptysacatlessthan12weeks
gestation
Latepregnancyloss Heartactivity lostafter12weeksgestation
Avoidterm abortion/spontaneousabortionasmay beconfusedwiththerapeutictermination
Embryo<10weeks Fetus>10 weeks
Variationinterminologyforresearch purposesincludese.g.yolksacmiscarriage(Kolte 2015)
Page 32 of 166
International guidelines for diagnosis of
miscarriage
DelayedMiscarriage
Page 33 of 166
DelayedMiscarriage
TRANSVAGINALSCAN
Embryo>7mmandnovisibleheartbeat
Or
Mean gestationsacdiameter(MSD)>25mm
andnoembryonicstructure
Or
Embryo<7mmorMSD<25mmandnoheart
beatafteratleast714days*
*variationinternationally dependsonpresenceofyolksacorembryoon
firstscan.14daysisSAFE
Why 25mm and 7mm for miscarriage?
Previous guidance:
USA: 16mm GSD, 5mm CRL
UK: 20mm GSD, 6mm CRL
Prospective Multicentre study:

false positive rates
MSD16 mm: 4.4% (95% CI 8.4% to 2.2%)
CRL 5 mm and no heartbeat: 8.3% (25.8% to 2.3%)
Intraobserver and interobserver variability
Page 34 of 166
Intraobserver variability
CRL MSD
CRL1 of first 95% PI for CRL1 MSD of first 95% PI for MSD of
observer (mm) of second observer (mm) observer (mm) second observer (mm)
5 [4.5-5.6] 17 [14.3-21.0]
6 [5.4-6.7] 18 [15.1-22.2]
7 [6.3-7.9] 19 [16.0-23.4]
10 [8.9-11.2] 20 [16.8-24.5]
20 [17.9-22.4] 21 [17.6-25.7]
30 [26.7-33.5] 22 [18.4-26.9]
PI = prediction interval
Pexsters 2011
What happens if we get it wrong?
Page 35 of 166
Miscarriage:Embryo>7mmandnovisibleheartbeat
CRL21.4mm
Dopplerultrasoundcanbeusedtoconfirm
(notessentialfordiagnosis)
Page 36 of 166
Miscarriage:Meangestationsacdiameter(MSD)
>25mmandnoembryonicstructure
Sacmaybeseentobecollapsing
Page 37 of 166
Miscarriage:Embryo<7mmorMSD<25mmandno
changeafter714days
IPUVI (Intrauterine pregnancy of uncertain viability)
YS
only
Small CRL
GS only
Page 38 of 166
The IPUVI Problem
Conservative approach to diagnosis of miscarriage means

more pregnancies classified as uncertain viability.
Sensitive home pregnancy tests means that women may

have a positive pregnancy test even before they have
missed a period.
Result is women attending for TVS in early pregnancy are

more likely to have an uncertain outcome and be asked to
undergo a repeat TVS at intervals of 714 days.
IPUVI classification in up to 25-30% of EPAU attenders
Bottomley 2009
Page 39 of 166
RCOG/NICE2012
IfCRL>7mmorMSD>25mmandnoFH
Seekasecondopinionontheviabilityofthe
pregnancyand/orperformasecondscana
minimumof7daysafterthefirstbeforemakinga
diagnosis
Ifrepeatscanindicatedafter7days
Furtherscansmaystillberequiredifembryonic
developmentbutnoFHyetvisible
RCOG/NICE2012
Recommendtransvaginal ultrasound
Consideratransabdominalultrasoundscanfor
womenwithanenlargeduterusorotherpelvic
pathology,suchasfibroidsoranovariancyst.
Differentcriteriafordiagnosisofmiscarriage
usingtransabdominalscan
Page 40 of 166
IF ANY POSSIBLE DOUBT ABOUT
MISCARRIAGE DIAGNOSIS
do nothing
IncompleteMiscarriage
Page 41 of 166
Diagnosis of incomplete miscarriage
Incomplete miscarriage = irregular heterogeneous echoes

within the endometrial cavity on TVS
Diagnosis of incomplete miscarriage

No validity for a cut-off value for endometrial thickness (e.g.
15 mm)
Endometrial thickness does not correlate with finding of

chorionic villi on histology or symptoms
Even with a thin endometrium of 2 mm or less, products of

conception can not be completely ruled out.
Sawyer 2007
Page 42 of 166
Doppler flow = retained products (incomplete miscarriage)
No Doppler flow does not rule out RPOC but less likely
Colour Doppler
ColourDopplerusefultofacilitate
differentialdiagnosisbetweenRPOC
andbloodclotswithinthecavity.
RPOCareusuallywellperfused,
whilstnoDopplersignalsarefound
originatinginbloodclots.
Page 43 of 166
Complete miscarriage
Absence of a previously visualised intrauterine pregnancy

with no retained products seen on transvaginal scan
Complete miscarriage
History and TVS empty uterus alone is insufficient to diagnose

a miscarriage if an intrauterine pregnancy has not been
previously confirmed as up to 6% underlying ectopic
pregnancy
Condous 2005
Page 44 of 166
Miscarriage prediction: Clinical features
Bleeding
55% miscarriage rate
Everett 1997
Previous pregnancy history

4% if all previous successful pregnancies
20% if at least one previous miscarriage
24% if only miscarriages previously
Regan 1989
Age
35yr 20% miscarriage
42yr 55% miscarriage
Andersen 2000
Page 45 of 166
Miscarriage prediction ultrasound markers
Increased CRL:GS ratio
Initially viable pregnancies
CRL
GS size
YS size
GS to CRL ratio
Regularity of GS
Subchorionic haematoma
Embryonic heart rate
Models
IVF women: MSD, CRL, FHR, maternal age, gestational age (AUC
0.87)
Choong 2003
Ultrasound , bleeding, demographics prediction rate for miscarriage of
85.7% (at a false positive rate of 30%)
Papaioannou 2011
Miscarriage prediction CRL deviation

CRL with gestation
80
70
60
Expected mean CRL

50
CRL (mm)
+2SD
40 -2SD
Viable
30
Non viable
20
10
0
28 38 48 58 68 78 88
GA (days from LMP)
Mukri BJOG 2008
Page 46 of 166
Miscarriage prediction Slow embryonic heart rate
Miscarriage prediction Empty amnion
Amnion develops from 7

weeks gestation therefore
if amnion visible then a 7
week size embryo would
also be expected
Page 47 of 166
Miscarriage prediction Subchorionic haematoma
Subchorionic haematoma
Crescent shaped, echofree areas

between the chorionic membrane
and myometrium
Presence has been associated with

4-33% risk of miscarriage
depending on gestational age
Subsequent contradictory findings

for role in early pregnancy loss
Associations with PPROM, Preterm

labour, PET
Page 48 of 166
Miscarriage prediction
1. What do the images show?

2. How would you interpret the
findings?
3. How would you have managed
the patient at first and subsequent
scan?
Miscarriage prediction: Chorionic Bump
Echolucent lesion arising within the chorion into GS

Uncertain pathogenesis (possibly haematoma)
2 x rate miscarrriage
Possibly increased 2nd trimester miscarriage
Sana 2013
Page 49 of 166
Summary so far
Miscarriage diagnosis if embryo > 7mm or MSD > 25mm or must

rescan in at least 7 days
NICE/ RCOG recommends second opinion
Making a diagnosis of miscarriage must take account of the inherent
variability in measurement and the different growth rates in the first
trimester
The expectant approach is unlikely to do harm and may in some
circumstances prevent inadvertent harm
Some soft markers of miscarriage can aid counselling and follow up
but are not considered diagnostic
Doppler flow is useful in confirming no embryonic heart beat and
helping differentiate retained products from blood clot
Diagnostic challenges
1. IncompletemiscarriageorPregnancyofUnknownLocation?
2. Incompletemiscarriageorbloodclot?
3. Incompletemiscarriageorcervical/scarpregnancy?
Page 50 of 166
Incomplete or PUL?
Firstpresentation.8weeksgestation.Moderatebleeding.
Incomplete or PUL?
Ifindoubt,treataspregnancyofunknownlocationandfollow
upwithserialhCG
Page 51 of 166
Page 52 of 166
Colour Doppler
ColourDopplerusefultofacilitate
differentialdiagnosisbetweenRPOC
andbloodclotswithinthecavity.
RPOCareusuallywellperfused,
whilstnoDopplersignalsarefound
originatinginbloodclots
HoweversomeRPOCareavascular
sosubjectiveappearancealso
important
Page 53 of 166
Gestation sac in cervix
Learning point: Remember to examine cervix

Differentiate miscarriage in progress from cervical ectopic as
miscarriage in progress will likely have :
Positive sliding sign
Absent peritrophoblastic flow
Usually no heart beat
Dont forget.sepsis
Leading cause of maternal deaths (CEMACE Saving
Mothers' Lives 2006 2008)
One third of deaths occurred before 24 weeks
May be sudden and catastrophic
Early recognition of signs of possible sepsis should be

actively sought and managed
Page 54 of 166
Summary
Do not use endometrial thickness when referring to RPOC
Use Doppler to support the diagnosis of RPOC vs clot
Examine the cervix
Expectant management is safe
Think sepsis
FAQs
Page 55 of 166
Does 3D help in diagnosis of miscarriage?
No evidence for role of 3D imaging in diagnosis of
miscarriage
What if gestation certain (IVF) and USS

findings are not compatible with
gestation?
Guidelines do not distinguish between IVF and naturally
conceived pregnancies
Diagnosis of miscarriage should err on side of caution but,
as long as discussed with the woman, the requirement for
rescan in 14 days may be flexibly applied
Page 56 of 166
Practical tips: What to say in practice?
Intrauterine pregnancy of uncertain viability
Pregnancy is correctly located (not ectopic)

A heart beat is not yet visible but the development is
/ is not as expected for the presumed gestation
We need to allow time for the pregnancy to develop
and reassess in 2 weeks (1 week if advanced GA)
There is a (small) chance of miscarriage meantime
and this is what to expect (no need to attend hospital,
but keep FU appt)
Practical tips: What to say in practice?
The wellbeing of a pregnancy is something about

which you would expect your doctor/nurse to be
certain about, so although the pregnancy does not
seem to have developed normally, we need to be
100% certain and will need to check again in 1
week before doing anything actively
Page 57 of 166
Practical tips: Information leaflets
Gives patients time to adjust to the
news before having to decide on
treatment
Reduces risk- ensures the

diagnosis is correct with 2
parameters to measure FH and
growth
Introduces 7 days expectant

management during which around
50% miscarry and return complete
saves interventions with cost
advantages
THANK YOU
Questions?
Page 58 of 166
Bibliography
Threatened miscarriage in general practice: diagnostic value of history taking and physical examination. Wieringa-de Waard et
al.,Br J Gen Pract. 2002 Oct;52(483):825-9
Terminology for pregnancy loss prior to viability: a consensus statement from the ESHRE early pregnancy special interest group.
Kolte AM1, Bernardi LA2, Christiansen OB3, Quenby S4, Farquharson RG5, Goddijn M6, Stephenson MD7; ESHRE Special
Interest Group, Early Pregnancy. Hum Reprod. 2015 Mar;30(3):495-8.
Updated and revised nomenclature for description of early pregnancy events.

Farquharson RG, Jauniaux E, Exalto N; ESHRE Special Interest Group for Early Pregnancy (SIGEP).Hum Reprod. 2005
Nov;20(11):3008-11.
The value of measuring endometrial thickness and volume on transvaginal ultrasound scan for the diagnosis of incomplete
miscarriage. Sawyer et al. Ultrasound Obstet Gynecol 2007 Feb; 29(2): 205209.
Do we need to follow up complete miscarriages with serum human chorionic gonadotrophin levels? Condous G, Okaro E, Khalid
A, Bourne T. BJOG. 2005 Jun;112(6):827-9.
Clinical significance of first-trimester chorionic bumps: a matched case-control study.

Sana Y, Appiah A, Davison A, Nicolaides KH, Johns J, Ross JA. Ultrasound Obstet Gynecol. 2013 Nov;42(5)
The optimal timing of an ultrasound scan to assess the location and viability of an early pregnancy.Bottomley C, Van Belle V,
Mukri F, Kirk E, Van Huffel S, Timmerman D, Bourne T.
Hum Reprod. 2009 Aug;24(8):1811-7
Clinical implications of intra- and interobserver reproducibility of transvaginal sonographic measurement of gestational sac and
crown-rump length at 6-9 weeks' gestation. Pexsters A, Luts J, Van Schoubroeck D, Bottomley C, Van Calster B, Van Huffel S,
Abdallah Y, D'Hooghe T, Lees C, Timmerman D, Bourne T. Ultrasound Obstet Gynecol. 2011 Nov;38(5):510-5
Incidence and outcome of bleeding before the 20th week of pregnancy: prospective study from general practice.Everett C. BMJ.
1997 Jul 5;315(7099):32-4.
Page 59 of 166
Pregnancyofunknownlocation(PUL)
ProfessorTomBourne
TommysNationalCentreforMiscarriageResearch
ImperialCollegeLondon
TomBourne:Disclosureofspeakersinterests
ResearchFundingandEquipment
SamsungMedison
RocheDiagnostics
SpeakingHonoraria
SamsungMedison
CharityFunding
ImperialCollegeCharity
KULeuven
TommysCharity
Accenture
Relevantcommittees
BoardInternationalSocietyforUltrasoundinObstetricsandGynecology(ISUOG)
ScientificcommitteeRoyalCollegeObstetriciansandGynaecologists (RCOG)
UltrasoundAdvisorycommitteeoftheRCOG
PresidentoftheAssociationofEarlyPregnancyUnits(AEPU)
BoardTommysNationalCentreforMiscarriageResearch
Page 60 of 166
LearningObjectives
Bytheendofthissessionyoushouldbeabletounderstandthe
evidencebasedmanagementofPregnancyofUnknownLocation:
ThecommonprogesteronebasedprotocolsusedtomanagePUL
ThecommonhCGbasedprotocolsusedtomanagePUL
HowhCGandprogesteronecanbecombinedinatwostepprotocol
includingaprediction model tobettermanagePUL
What is a PUL?
UK US
Emptyuterus,nosignsofan Yes Yes
IUPorEP truePUL
Possibleearlyintrauterine No Yes
gestationalsac
Possibleextrauterine No Yes
inhomogeneousmass
Possiblesmallamountof ?Yes ?Yes

retainedproductsof
conception
Page 61 of 166
PUL
Followcanbechaoticwith
multiplevisits
multiplebloodtests
multiplescans
especiallyifpatientsareseenoutofhours
Thereneedtobestrict,evidencebased
managementprotocolsinplace
Manydifferentmanagementprotocolsexist
Page 62 of 166
Sensitivehomepregnancyteststhatdate
Earlierscans:theopportunityforerrorisincreased
At2834days 70%PULrate
Bottomley,BourneetalHR2009
Currentbiomarkersinclinicaluse
progesterone
hCG
Page 63 of 166
Progesterone
singlevisitstrategy
Dayetal(UOG2009)
n=1110,prospective,1centre
Dischargedifprogesteroneatday010nmol/l 47%
12ectopics withaprogesterone10nmol/l
6/12ectopics neededintervention
Cordina etal(BJOG2011)
n=252,prospective,1centre
Dischargedifprogesteroneatday010nmol/l 37%
5ectopics (2neededsurgery)
Overallinterventionrate=1.6%
10%losttof/u
Page 64 of 166
Currentbiomarkersinclinicaluse
progesterone
hCG
Discriminatoryzoneisanoutdatedconcept
n=527consecutivePULattendinganEPU
Page 65 of 166
PUL Results: n = 518
78%ofectopicsmissedhCG<1000U/L
Prog
hCG
FailingPUL ViableIUP Ectopic
hCG
hCG ratio
hCG 48hours/hCG 0hours
LikelyfailingPUL Likelyectopic LikelyongoingIUP
hCG ratio
hCG ratio hCG ratio
0.87
<0.87 >1.66
1.66
Page 66 of 166
PregnancyofUnknown
Location
triage
LOWrisk(6090%) HIGHrisk(1040%)
Intrauterine Ectopic
FailingPUL PPUL
PredictionmodelsutilisinghCG:
InitialhCG
M4model
hCG ratio
Page 67 of 166
Guha etal(HR2014)
n=1271,prospective,3centres
Comparedperformanceofprogesteronecutoffsv.hCG ratiov.M4model
Percentageclassifiedashighrisk
Data Prog hCG ratio M4model
Outcome (<10nmol/L) (0.87x1.66) (riskEP5%)
FailedPUL 24% (2028%) 10% (812%) 14% (1117%)
incorrect IUP 95% (9297%) 15% (1120%) 37% (3143%)
Ectopic 76% (6783%) 63% (5371%) 84% (7690%)

correct
Classified 52% (4956%) 84%(8186%) 73%(7076%)

LOWRISK
NPV 95% (9397%) 96% (9497%) 98%(9699%)
MISSEDEP 1in21 1in23 1in48

DOR 3.54 13.1 19.3
Guha etal(HR2014)
n=1271,prospective,3centres
Comparedperformanceofprogesteronecutoffsv.hCG ratiov.M4model
Percentageclassifiedashighrisk
Data Prog hCG ratio M4model
Outcome (<10nmol/L) (0.87x1.66) (riskEP5%)
FailedPUL 24% (2028%) 10% (812%) 14% (1117%)
incorrect IUP 95% (9297%) 15% (1120%) 37% (3143%)
Ectopic 76% (6783%) 63% (5371%) 84% (7690%)

correct
Classified 52% (4956%) 84%(8186%) 73%(7076%)

LOWRISK
NPV 95% (9397%) 96% (9497%) 98%(9699%)
MISSEDEP 1in21 1in23 1in48

DOR 3.54 13.1 19.3
Onevisit Twovisits
Page 68 of 166
Arepredictionmodelsthewayforward?
hCG progesterone
2stepmodel
Methods
Diagnosticaccuracystudy
Secondaryanalysisofprospectively,consecutivelycollecteddata
EPAUattwoLondonbaseduniversityteachinghospitals:
StGeorges:07/2003 02/2007
QueenCharlottes&Chelsea:04/2009 12/2013
Datausedtodevelopa2stepriskpredictionmodel
Page 69 of 166
Data Failed PUL I UP Ectopic Total
All 1450 (52.7%) 1002 (36.4%) 301 (10.9%) 2753
Development data
All 785 (54.2%) 501 (34.6%) 163 (11.2%) 1449
SGH 455 (49.4%) 375 (40.7%) 91 (9.9%) 921
QCCH 330 (62.5%) 126 (23.9%) 72 (13.6%) 528
Validation data
All 665 (51.0%) 501 (38.4%) 138 (10.6%) 1304
SGH 443 (51.2%) 344 (39.8%) 78 (9.0%) 865
QCCH 222 (50.6%) 157 (35.8%) 60 (13.7%) 439
STEP 1:
Progesterone 2?
YES NO
DO NOT perform
48 hr HCG
UPT in 2 weeks
Page 70 of 166
STEP 1:
Progesterone 2? Go to STEP 2
YES NO
DO NOT perform
48 hr HCG
UPT in 2 weeks
STEP 1: STEP 2:
Progesterone 2? Perform 48 hr HCG

Go to STEP 2
Put data into the M6 model

YES NO
DO NOT perform
48 hr HCG
UPT in 2 weeks
Page 71 of 166
STEP 1: STEP 2:
Progesterone 2? Perform 48 hr HCG

Go to STEP 2
Put data into the M6 model

YES NO
DO NOT perform
48 hr HCG Model states Model states
Model states
LOW RISK LOW RISK
HI GH RI SK
FPUL IUP
UPT in 2 weeks
hCG + REPEAT UPT in US in

SCAN in 48 hr s 2 weeks 1 week
STEP1:progesteronecutoffs
Page 72 of 166
STEP1:progesteronecutoffs
Cut-off to define PUL classified Negative EP classified Non-EP classified
low-risk as at low-risk predictive value as at high-risk as at high-risk
Prog 2 200/1449, 13.8% 197/200, 98.5% 160/163, 98.2% 1089/1286, 84.7%
Prog 3 293/1449, 20.2% 286/293, 97.6% 156/163, 95.7% 1000/1286, 77.8%
Prog 4 377/1449, 26.0% 367/377, 97.3% 153/163, 93.9% 919/1286, 71.5%
Prog 5 445/1449, 30.7% 429/445, 96.4% 147/163, 90.2% 857/1286, 66.6%
Prog 6 505/1449, 34.8% 486/505, 96.2% 144/163, 88.3% 800/1286, 62.2%
Prog 7 549/1449, 37.9% 526/549, 95.8% 140/163, 85.8% 760/1286, 59.1%
Prog 8 583/1449, 40.2% 555/583, 95.3% 136/163, 83.3% 731/1286, 56.8%
Prog 9 609/1449, 42.0% 579/609, 95.2% 134/163, 81.9% 707/1286, 55.0%
Prog 10 636/1449, 43.9% 603/636, 94.9% 130/163, 79.9% 683/1286, 53.1%
STEP2:M6model
M6P M6NP
(modelwithprogesterone) (modelwithnoprogesterone)
InitialhCG InitialhCG
Initialprogesterone hCG ratio
hCG ratio
Page 73 of 166
Testperformancedata
Negative
Data PUL classified Sensitivity for False positive
predictive
Classification approach as low-risk EP rate
value
Validation data
210/1304, 206/210, 134/138, 960/1166,
Step 1 only:
Progesterone cut-off
16.1% 98.1% 97.1% 82.3%
(14.2-18.2) (95.0-99.3) (92.4-98.9) (80.0-84.5)
789/1304, 782/789, 131/138, 384/1166,
M6P model in isolation 60.5% 99.1% 94.9% 32.9%
(57.1-63.8) (98.1-99.6) (89.4-97.6) (29.5-36.5)
716/1304, 706/716, 128/138, 460/1166,
M6NP model in isolation 54.5% 98.6% 92.5% 39.9%
(49.8-59.2) (97.3-99.2) (86.4-96.1) (35.0-45.1)
810/1304, 799/810, 127/138, 367/1166,
Two-step protocol:
Step 1 + M6P model 62.1% 98.6% 92.0% 31.5%
(58.8-65.3) (97.5-99.3) (85.9-95.6) (28.1-35.0)
754/1304, 740/754, 124/138, 426/1166,
Two-step protocol:
57.7% 98.1% 89.6% 36.6%
Step 1 + M6NP model
(53.2-62.1) (96.8-98.9) (83.0-93.9) (32.0-41.5)
921/1304, 895/921, 112/138, 271/1166,
M4-based triage 70.6% 97.2% 81.4% 23.2%
(68.0-73.1) (95.9-98.1) (73.9-87.2) (20.8-25.8)
572/1304, 542/572, 108/138, 625/1166,
Single visit prog 10nmol/l 43.8% 94.7% 78.1% 53.6%
(41.1-46.6) (92.5-96.3) (70.3-84.3) (50.7-56.5)
Results(gaugeplots)
M4based 2stepwithM6P
~17%atstep1
~45%atstep2
%Lowrisk
71% 62%
NPV(%)
97% 99%
SensitivityEP(%)
81% 92%
Plots created using infogr.am
Page 74 of 166
Diagnosticaccuracy
study
Clinical
study
2stepclinicalstudy
Multicentre prospectivecohortstudy
C&WH WEXHAM HILLINGDON

(PULrate@12%) (PULrate@8%) (PULrate@15%)
QCCH SMH WMUH R.SURREY

(PULrate@10%) (PULrate@10%) (PULrate@8%) (PULrate@13%)
2645PUL
117(4.4%)incomplete
outcomedata
2528PUL
260(16.7%)LFU
2268PUL
1280(56.4%) 452(19.9%) 269(11.9%) 205+62(11.8%)

FPUL VIUP NVIUP Ectopic/PPUL
Page 75 of 166
EP/PPULmisclassifications:SUMMARY
STEP1 STEP2
(prog cutoffs) (M6model)
PROGCUTOFF2
&10ATWMUH PROGCUTOFF2
24.1%(563/2333) 19.5%(455/2333) 54.9%(990/1802)
PULaslowrisk PULaslowrisk PULaslowrisk
97.0%(546/563) 97.8%(445/455) 99.2%(982/990) 0.8%(8/990)

CORRECT CORRECT CORRECT INCORRECT
3.0%(17/563) 2.2%(10/455)
INCORRECT INCORRECT
Page 76 of 166
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Page 78 of 166
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Page 80 of 166
Summary
ThereisaclinicalneedtorationalizethemanagementofPUL
SeveralmanagementprotocolsbasedonhCG andprogesteroneareusedincurrentclinical
practice
Thetestperformanceofanyprotocolwillbeinfluencedbythecountry,legalramifications,
qualityofscanning,PULrate..
ThereremainsaquestionmarkovertherelevanceofmisclassifyingsomeEPaslowriskPUL
The2stepmodelutilizinghCG andprogesteronelevelsisoneofthelargestdatasetsonPUL
todate
Wearecurrentlyperformingamulticentre interventionstudytoassessitsutilityinclinical
practice
Wehavedevelopedthemodelintoauserfriendlyappforsmartphones
Page 81 of 166
Acknowledgments
MissJessicaFarren ProfessorBenVanCalster
MissNicolaMitchellJones ProfessorTomBourne
Mr FrancisAyim ProfessorDirkTimmerman
MissBaljinder Chohan MissCeciliaBottomley
MissBramara Guruwadahyarhalli MissAnjaliKothari
MissSayanti Ghosh Mr Vathanan Veluppillai
MissMelodyTaheri MissSharmistha Guha
Mr OsamaAbughazza MissDeborahGould
MissMayaAlMemar MissShahla Ahmed
MissCatriona Stalder MissSophieTapp
App:searchearlypregnancyLeuvenintheappstore
Freewebsite:www.earlypregnancycare.org
Furtherreadingandreferences
TheclinicalperformanceoftheM4decisionsupportmodeltotriagewomenwithapregnancyofunknownlocationas
atloworhighriskofcomplications. BobdiwalaS,GuhaS,VanCalsterB,Ayim F,MitchellJonesN,AlMemarM,Mitchell
H,StalderC,BottomleyC,KothariA,TimmermanD,BourneT.Hum Reprod.2016Jul;31(7):535.
ManagingpregnancyofunknownlocationbasedoninitialserumprogesteroneandserialserumhCGlevels:
developmentandvalidationofatwosteptriageprotocol. VanCalsterB,BobdiwalaS,GuhaS,VanHoorde K,AlMemar
M,HarveyR,FarrenJ,KirkE,CondousG,SurS,StalderC,TimmermanD,BourneT.UltrasoundObstetGynecol.2016
Nov;48(5):642649.
Triagingpregnanciesofunknownlocation:theperformanceofprotocolsbasedonsingleserumprogesteroneor
repeatedserumhCGlevels. GuhaS,Ayim F,LudlowJ,SayasnehA,CondousG,KirkE,StalderC,TimmermanD,Bourne
T,VanCalsterB.HumReprod.2014May;29(5):93845.
Rationalizingthemanagementofpregnanciesofunknownlocation:temporalandexternalvalidationofarisk
predictionmodelon1962pregnancies. VanCalsterB,AbdallahY,GuhaS,KirkE,VanHoorde K,CondousG,
PreislerJ,Hoo W,StalderC,BottomleyC,TimmermanD,BourneT.HumReprod.2013Mar;28(3):60916.
ClassificationofpregnanciesofunknownlocationaccordingtofourdifferenthCGbasedprotocols. Fistouris J,BerghC,
Strandell A.HumReprod.2016Oct;31(10):220311.
Diagnosingectopicpregnancy andcurrentconceptsinthemanagementofpregnancyofunknownlocation.
KirkE,BottomleyC,BourneT.HumReprodUpdate.2014MarApr;20(2):25061
Introductionofasinglevisitprotocolinthemanagementofselectedpatientswithpregnancyofunknown
location:aprospectivestudy. CordinaM,SchrammGajraj K,RossJA,Lautman K,JurkovicD.BJOG.2011
May;118(6):6937.
Theoptimaltimingofanultrasoundscantoassessthelocationandviabilityofanearlypregnancy. Bottomley
C,VanBelleV,MukriF,KirkE,VanHuffelS,TimmermanD,BourneT.HumReprod.2009Aug;24(8):18117.
Page 82 of 166
AdditionalSlides notused
ROCcurvesfordiscriminatingEPfromFPUL/IUP.
Theperformanceattheriskthresholdof5%isindicatedbyblackdots
Page 83 of 166
N=1900PUL
hCGratio>1.66
ViableIUP>3000
SerumhCG@3000
EP<1000
PULtriagebyM4:
HighriskareaM4isa
Simplemathematical
Modelthatgivesarisk
basedontheinitialserum
hCGratio<0.8
hCGandthehCGratio
Results(differentvisualization)
M4based 2stepwithM6P
FPUL/IUP orEP
classifiedasat
lowriskafter
1visit
FPUL/IUP orEP
classifiedasat
lowriskafter
2nd visit
FPUL/IUP orEP
classifiedasat
Highriskafter
2nd visit
Plots created using infogr.am
Page 84 of 166
TheissuecomesdowntowhetherEPlabeledlowriskaredangerous
andvalueofaoneortwovisitstrategy
DependsonwhichcasesarebeinglabeledasaPUL
dopublishedstudiesreflectrealworld?
Dependsonqualityofthescanning soaresome
unitsEPintheirPULpopulationriskierthanothers?
Dependsonthecultureandcountry perceivedrisk
ofmissedectopicpregnancy
Naturalhistoryofectopicpregnancy
HowmanynewpatientsdoyouseeinyourEPUeachyear?
WhatisyourPULrate? i.e.the%ofnewpatientslabeledaPUL
OfyourPULhowmanyturnouttobeectopicpregnancies?
ConsidermissedEP:
Arewetalkingaboutthesamepopulations?
PULrateinliteraturerangesfrom5to42%
PULrateinbetterknownpapersis810%(KirkandCordina)
132of354PULwereEP
(37%)
133of1271PULwereEP
(10.5%)
85outof1110PULwereEP
(7.6%)
284outof1400wereEP
(20%)
Page 85 of 166
App
53
Page 86 of 166
EctopicPregnancy
EmmaKirk
MRCOGMD
Conflict of Interest
None
Page 87 of 166
Objectives
To recognize the role of ultrasound in the

diagnosis of ectopic pregnancies
To describe the sonographic criteria for

tubal and non-tubal ectopic pregnancies
Diagnosis of Ectopic Pregnancy
Historically at the time of surgery

Haemoperitoneum
Distended Fallopian tube
Signs of tubal rupture
Chorionic villi within Fallopian tube
1970s introduction of laparoscopy
1970s diagnostic ultrasound

Inability to visualise an intrauterine pregnancy
Page 88 of 166
Ultrasound Diagnosis
Transvaginal sonography (TVS)
High sensitivity (87.0-99.0%) and

specificity (94.0-99.9%)
Braffman et al., 1994, Shalev et al., 1998, Atri et al., 2003, Condous et al., 2005
Diagnosis based on positive visualisation

of an extra-uterine pregnancy, rather than
the inability to visualise an intra-uterine
pregnancy
Positive Pregnancy Test
TVS
70-90% 10-30%
Diagnostic Non-diagnostic
Intra-Uterine Ectopic Pregnancy Pregnancy of

Pregnancy (IUP) (EP) Unknown Location
Failing IUP EP Persistent

PUL PUL
Page 89 of 166
Diagnosis on the initial USS
Studies reporting high sensitivities

examined women using TVS immediately
prior to laparoscopy, and correlated
sonographic features to surgical findings
Results are therefore possibly misleading

as not all ectopic pregnancies would have
been visualised on the initial TVS
examination
Sensitivity of TVS to detect ectopic pregnancy

Kirketal.,2007.HumReprod
5318cases,122ectopicpregnancies
Initial TVS:
Sensitivity 73.9% (95% CI: 55.7 81.2%)
Specificity 99.9% (99.8-100.0%)
PPV 96.7% (91.6 99.2%)
NPV 99.4% (99.1 99.6%)
Overall (including follow-up scans):

Sensitivity 98.3% (95% CI: 94.1 - 99.8%)
Specificity 99.9% (99.8 - 100.0%)
PPV 97.5% (92.9 - 99.5%)
NPV 100% (99.9 - 100.0%)
Page 90 of 166
Initial TVS:
Sensitivity 73.9% (95% CI: 55.7 81.2%)
Specificity 99.9% (99.8-100.0%)
PPV 96.7% (91.6 99.2%)
NPV 99.4% (99.1 99.6%)

Sensitivity 98.3% (95% CI: 94.1 - 99.8%)
Specificity 99.9% (99.8 - 100.0%)
PPV 97.5% (92.9 - 99.5%)
NPV 100% (99.9 - 100.0%)

Initial TVS:
Sensitivity 73.9% (95% CI: 55.7 81.2%)
Specificity 99.9% (99.8-100.0%)
PPV 96.7% (91.6 99.2%)
NPV 99.4% (99.1 99.6%)

Sensitivity 98.3% (95% CI: 94.1 - 99.8%)
Specificity 99.9% (99.8 - 100.0%)
PPV 97.5% (92.9 - 99.5%)
NPV 100% (99.9 - 100.0%)
Page 91 of 166
Why are some ectopic pregnancies missed
on the initial TVS?
Initial TVS
Initial TVS result

Ectopic PUL p-
Pregnancy value
n 353 58 -
Maternal age 30.4 (5.9) 32.0 (6.3) 0.0551
(years) Mean (SD)
Bleeding n (%) 216 (61.2) 39 (67.2) 0.4657
Pain n (%) 233 (66.0) 34 (58.6) 0.2997
ET mm Mean (SD) 10.1 (5.7) 11.1 (5.3) 0.098
Page 92 of 166
Initial TVS
Initial TVS result

Ectopic PUL p-
Pregnancy value
Gestational age 45.6 (14.5) 41.4 (13.5) 0.0317
(days) Mean (SD)
hCG IU/L Median 1286 (3384, 478- 635 (1796, 234- 0.0010
(IQR) 3826) 2030)
Prog nmol/L 19 (27, 9-36) 30 (26, 19-45) 0.0095
Median (IQR)
TVS to diagnose EP
TVS to visualise ectopic pregnancy

Initial TVS Subsequent TVS p-value
hCG IU/L Median (IQR) 1286 (3384, 473-3826) 1259 (2657, 340-2997) 0.2431
Prog nmol/L Median 19 (27, 9-36) 20 (17, 11-28) 0.7334
(IQR)
Appearance on TVS:
Inhomogeneous mass 222 (62.9) 25 (71.4)
n (%) 0.1029
Empty gestational sac 77 (21.8) 9 (25.7)
n (%)
Gestational sac with 54 (15.3) 1 (2.9)
yolk sac/fetal pole n (%)
Mean size of ectopic 22.2 (9.3) 15.4 (5.3) <0.0001
mass mm (SD)
Page 93 of 166
Why are some ectopic pregnancies missed
on the initial TVS?
Lower mean gestational age
Lower mean initial hCG
Higher mean progesterone level at presentation
They are probably too small and too early in

the disease process
Scanning Ectopic Pregnancies
1. Demographics
2. Presentingcomplaints
3. SerumBiochemistry
4. USSfindings
Endometrium
FreePelvicFluid
Visualizationofanectopicmass
Page 94 of 166
Demographics
Medianmaternalage31years(1645years)
MediangestationalageaccordingtoLMP44days(11104days)
Gestationalage<6/40 30.6%
Parity0(07)
Historyof1miscarriage18.5%
Historyof1termination19.4%
Historyof1ectopicpregnancy9.5%
*Datafrom422consecutivetubalectopicpregnanciesKirketal.,2008
Presenting Complaints
1/3rd havenoclinicalsignsandupto10%noclinicalsymptoms(Tay
etal.,2000,Kaplanetal.,1996)
Painandbleeding41.7%
Painalone20.3%
Bleedingalone23.2%
Datafrom422consecutivetubalectopicpregnanciesKirketal.,2008
Page 95 of 166
Serum Biochemistry
InitialserumhCGlevel1299IU/L(6129,956IU/L)
InitialserumhCGlevel<500IU/L24.9%
Initialprogesteronelevel19nmol/L(1178nmol/L)
Serum Biochemistry
InitialserumhCGlevel1299IU/L(6129,956IU/L)
InitialserumhCGlevel<1000IU/L41.7% *45%
Initialprogesteronelevel19nmol/L(1178nmol/L)
*hCG<1000IU/L 72%visualisedontheinitialTVS
*hCG>1000IU/L 83%visualisedontheinitialTVS
*Datafrom697consecutivetubalectopicpregnancies unpublished
* Datafrom422consecutivetubalectopicpregnanciesKirketal.,2008
Page 96 of 166
Empty uterus.
Endometrium
Nospecificendometrialappearancethatcanbe
usedtodiagnoseanectopicpregnancy
*ET9.3mm(1.7 36.0mm)
*24.1%Disrupted75.8%Intact
Pseudosacreportedinupto20%ofcases
Mayoccasionallycontaininternaldebris ?embryonic
structures
Page 97 of 166
Endometrium
Free Fluid..
Page 98 of 166
Free Fluid
Smallamountofanechoicfluidcommoninintra and
extrauterinepregnancies
Echogenicfluidpresentin2856% (Nybergetal.,1991,
Fleischeretal.,1990)
*Anechoicfreefluidin19.5%
*Echogenicfluidin35.8%
AmountoffluidfoundonTVScorrelateswellwith
operativefindings
Significantifreachesfundusofuterus,isinutero
vesicalpouchorMorrisonspouch
Tubal Ectopic Pregnancy

Gestational sac and CRL
or yolk sac
MedianhCG9072IU/L
*19% *Cardiacactivityin29%
*5.5%ofallvisualisedEPs
Range378 129,956IU/L
Page 99 of 166
Gestational sac and CRL or yolk sac
Empty Gestational Sac
MedianhCG1576IU/L
Range63 47,302IU/L
*20%
Page 100 of 166

Empty Gestational Sac

Inhomogeneous Mass
MedianhCG667IU/L
Range10 31,169IU/L
*62%
Page 101 of 166

Inhomogeneous Mass
Interstitial Ectopic Pregnancy

Empty uterine cavity 24%ofallectopicpregnancies
Gestational sac or
trophoblastic mass located in
the interstitial area
surrounded by a continuous
rim of myometrium
Interstitial line sign ( thin

echogenic line extending
from central uterine cavity
echo to periphery of
interstitial sac)
Page 102 of 166

Cornual Ectopic Pregnancy
A single interstitial portion of Implantationinthenon
Fallopian tube in the main communicatinghornofa
uterine body unicornuateuterus.
1in76,000pregnancies
A gestational sac or
trophoblastic mass mobile 0.27%ofallectopics
and separate from the main
uterine body but surrounded
by myometrium
A vascular pedicle joining the

gestational sac to the
unicornuate uterus
Cervical Ectopic Pregnancy

Empty uterine cavity
Barrel shaped cervix
Gestational sac or
trophoblastic mass below
level of the internal os
Absence of sliding sign
(when pressure is applied to cervix using the
probe in a miscarriage , the gestational sac
slides against the endocervical canal, but
does not in an implanted cervical
pregnancy) <1%ofallectopicpregnancies
Evidence of peritrophoblastic
flow on Color Doppler
examination
Page 103 of 166

Caesarean Section Scar Pregnancy
Gestational sac or
trophoblastic mass located
anteriorly at the level of the
internal os covering the
visible or presumed site of
the previous lower uterine
segment caesarean section
scar
Absent sliding sign
Evidence of peritrophoblastic
flow on color Doppler 1in1800pregnancies
examiantion
6%ofectopicsinwomen
withapreviousLSCS
Ovarian Ectopic Pregnancy
Gestational sac or
trophoblastic mass with
a wide echogenic ring
on or within the ovary,
generally seen
surrounded by ovarian
cortex and seen
separately from the
corpus luteum Upto3%ofallectopic
pregnancies
Page 104 of 166

Intra-mural Ectopic Pregnancy
Gestational sac or
trophoblastic mass
completely surrounded by
myometrium and separate to
the endometrial cavity
Rare
Riskfactors:IVF,adenomyosis,
uterinetraumafrom
instrumentation
Heterotopic Pregnancy
An ectopic pregnancy with an
intra-uterine pregnancy
1 in 7,500 - 30,000
spontaneous conceptions
1-3 in 100 pregnancies

conceived via ART
Page 105 of 166

Abdominal Pregnancy
No evidence of a dilated
Fallopian tube or complex
adnexal mass
Gestational sac or 1 original implantation site is

trophoblastic mass within the peritoneal cavity
surrounded by loops of
bowel and separated by 2 result of tubal abortion
peritoneum and re-implantation into the
abdominal cavity
Summary
TVS has a high sensitivity for the detection of
ectopic pregnancy:
Diagnosis is based on positive visualisation of an

ectopic mass
~75% of ectopic pregnancies can be visualised on the

initial TVS examination
Those missed on the initial TVS should be classified as

pregnancies of unknown location
Overall >90% can be visualised on TVS prior to

treatment
Agreement needed on diagnostic sonographic criteria
Page 106 of 166

The adnexa and other pathology
Wouter Froyman, MD
Department of Development and Regeneration

KU Leuven
Department of Obstetrics and Gynaecology
University Hospitals KU Leuven
No conflicts of interest to declare
Page 107 of 166

Learning objectives
Adnexal pathology in pregnancy

Incidence
o
o Natural history
o Ultrasound features of adnexal
lesions
Other pelvic pathology in pregnancy
Conclusions
1. Adnexal pathology in pregnancy
Routine obstetric ultrasound increased detection

Incidence highly variable 1/81 to 1/8000 pregnancies
(differences in pregnancy duration, ultrasound
criteria)
o Incidence of malignancy 1-8%
Majority (up to 71%) resolve spontaneously or
decrease in size
o High threshold for intervention!
o Simple morphology, <5-6 cm, diagnosis <16
weeks of gestation vs large masses with more
complex morphology
Hoover etal,AmJObstet Gynecol 2011
Page 108 of 166

Risk of torsion decreases with duration of

pregnancy (1-3%).
Ultrasound triage benign vs malignant
o Subjective assessment
o Diagnostic models (RMI, IOTA); (!) Not (yet)
validated in pregnant population
Need for standardised description of
ultrasound features non-pregnant population
o IOTA terms and definitions
Condous etal,UltrasoundObstet Gynecol 2004
Unilocular
Unilocular
-solid
Multilocular-
solid
Multilocular
Solid
Timmermanetal,UltrasoundObstet Gynecol 2000 6
Page 109 of 166

Implication for management: expectant -

ultrasound-guided drainage surgery
Risk to the pregnancy from surgical
intervention versus risk of malignancy
Benign adnexal lesions
Non-neoplastic (functional) ovarian lesions
Benign ovarian neoplasms
Benign non-ovarian lesions
Page 110 of 166

Follicular cyst/simple cyst
Anovulatory follicles
Unilocular, thin-walled, anechoic
<8-10 cm
Resolve spontaneously
Page 111 of 166

Follicular cyst
11
Corpus luteum cysts
Ovulation
Thick-walled, ring of fire, spider web
appearance
Resolve after 14-16 weeks of gestation
Page 112 of 166

Corpus luteum cysts
13
Haemorrhagic cysts
14
Page 113 of 166

Haemorrhagic cysts
15
Haemorrhagic cysts
16
Page 114 of 166

Luteoma of pregnancy
Rare, unilateral or bilateral (50%), solid,

hypo-echoic, highly vascularised
Asymptomatic or virilisation (30-35%)
Regress post-partum
Chiangetal, JUltrasoundMed 2004
Luteoma of pregnancy
Imagescourtesy ofProf.LilValentin 18
Page 115 of 166

Theca-lutein cysts
Hyperreactio luteinalis
Bilateral thin-walled multilocular cysts
(spoke wheel appearance)
Asymptomatic or pain (pressure, torsion,
haemorrhage)
Virilisation (25%)
Regress later in pregnancy or after delivery
VanHolsbeke etal,UltrasoundObstet Gynecol 2009
Theca-lutein cysts
Page 116 of 166

Page 117 of 166
Theca-lutein cysts
23
Theca-lutein cysts
24
Page 118 of 166

Theca-lutein cysts
25
Theca-lutein cysts
26
Page 119 of 166

Mature teratomas/dermoid cysts
Most common non-functional pathology

Unilocular with mixed echogenicity
(Rokitansky nodule, dermoid mesh),
acoustic shadowing, minimal
vascularisation.
Page 120 of 166

29
30
Page 121 of 166

Endometrioma
Unilocular with low-level or ground glass

echogenicity ( old blood), limited
vascularity
May have atypical features
o ! Decidualisation ( high progesterone)
DD malignancy
features resolve after pregnancy
Mostly asymptomatic
Mascilini etal,UltrasoundObstet Gynecol 2014
Endometrioma
32
Page 122 of 166

Endometrioma
33
Endometrioma
34
Page 123 of 166

Endometrioma
35
Cystadenomas
of benign adnexal epithelial neoplasms

Serous: Unilocular or multilocular, smooth,
thin-walled, anechoic cysts. Bilateral in
15%. Mean size limited to 5-8 cm.
Mucinous: Multilocular (often
innumerable), thin-walled, low-level
echogenicity. Unilateral. Large!!
Hormonally insensitive, limited vascularity
Page 124 of 166

Cystadenofibromas
Relatively rare, serous or mucinous

Unilocular-solid or multilocular-solid
Thin-walled, anechoic or low-level
echogenic content, solid component
(papillary projection), subtle shadowing,
low to moderate vascularity
Fibromas/fibrothecomas
Relatively rare
Round or oval, solid, regular lining, stripy
or fan-shaped shadows, vascularity
peripheral and limited
Paladini etal,UltrasoundObstet Gynecol 2009
Page 125 of 166

39
40
Page 126 of 166

Hydrosalpinx
Acute pelvic inflammatory disease rare

during pregnancy
Chronic salpingitis
Tubular, thin-walled, anechoic content,
incomplete septa, beads-on-a-string
Generally stable throughout pregnancy
Mostly asymptomatic
Page 127 of 166

Hydrosalpinx
43
Hydrosalpinx
44
Page 128 of 166

Para-ovarian cysts
Broad ligament
Thin-walled, unilocular, anechogenic
Separable from the ovary
Minimal vascularisation
No clinical significance
Malignant adnexal lesions
Non-epithelial tumours (germ cell, sex cord

stromal tumours)
Ovarian tumours with low malignant potential
Epithelial ovarian cancer
Multilocularity, wall irregularities, papillary

projections, other solid components.
Ascites, peritoneal implants, omental cake.
Page 129 of 166

47
2. Other pelvic pathology in pregnancy
Peritoneal pseudocysts
Leiomyomas/fibroids
Appendicitis
Pelvic kidney
Page 130 of 166

Peritoneal pseudocysts
Collections of peritoneal fluid entrapped by

adhesions.
Multilocular cysts, multiple complete and
thin septa, moving upon pushing (flapping
sail)
Sharp angles, following surrounding
structures
Mostly asymptomatic
Peritoneal
pseudocyst
50
Page 131 of 166

Leiomyomas/fibroids
Most common solid masses in pregnancy

(1.4-2%)
Intramural, pedunculated or in broad
ligament
Round masses, variable echogenicity,
peripheral vascularisation, presence of
acoustic shadowing.
Can grow during pregnancy focal pain.
Red degeneration: complex morphology,
cystic areas
Appendicitis
Most common cause of non-obstetric

surgery during pregnancy.
Clinical presentation often misleading (if
retro-caecal or behind gravid uterus)
Non-compressible tubular, blind-ending
structure, target sign.
Haider etal,JUltrasoundMed 2006
Page 132 of 166

Appendicitis
Imagescourtesy ofProf.LilValentin 53
Pelvic kidney
Congenital renal ectopia or after renal

transplantation.
Often clinically asymptomatic.
Rounded or elliptical shape with central
echogenic interface of renal pelvis.
Page 133 of 166

Pelvic kidney
55
3. Conclusions
Adnexal pathology in pregnancy is not very common

Most lesions are functional and will spontaneously resolve
o High threshold for surgical intervention!
Need for standardised description of ultrasound findings
Most lesions share characteristics which make them easy
to be recognised by subjective assessment
Endometriomas can undergo decidualisation (rounded,
smooth, vascularised papillary projections, ground glass
content)
o DD BOT: irregular papillary projections, no ground glass
Uterine fibroids are very common and when pedunculated
challenging to differentiate from adnexal masses
56
Page 134 of 166

References
Hoover K, Jenkins TR. Evaluation and management of adnexal mass in pregnancy. Am J Obstet Gynecol
2011; 205:97-102.
Condous G, Khalid A, Okaro E, Bourne T. Should we be examining ovaries during pregnancy? Prevalence
and natural history of adnexal pathology detected at first trimester sonography. Ultrasound Obstet Gynecol
2004; 24:62-6.
Timmerman D, Valentin L, Bourne T, Collins WP, Verrelst H, Vergote I. Terms, definitions and measurements
to describe the sonographic features of adnexal tumors: a consensus opinion from the International Ovarian
Tumor Analysis (IOTA) group. Ultrasound Obstet Gynecol 2000;16:500-5.
Sayasneh A, Ekechi C, Ferrara L, Kaijser J, Stalder C, Sur S et al. The characteristic ultrasound features of
specific types of ovarian pathology (review). Int J Oncol 2015; 46(2):445-458.
Chiang G, Levine D. Imaging of adnexal masses in pregnancy. J Ultrasound Med 2004; 23:805-19.
Van Holsbeke C, Amant F, Veldman J, De Boodt A, Moerman Ph, Timmerman D. Hyperreactio luteinalis in a
spontaneously conceived singleton pregnancy. Ultrasound Obstet Gynecol 2009; 33:371-373.
Mascilini F, Moruzzi C, Giansiracusa C, Guastafierro F, Savelli L, De Meis L et al. Imaging of gynecological
disease: clinical and ultrasound characteristics of decidualized endometriomas surgically removed during
pregnancy. Ultrasound Obstet Gynecol 2014; 44:354-360.
Paladini D, Testa A, Van Holsbeke C, Mancari R, Timmerman D, Valentin L. Imaging in gynecological disease
(5): clinical and ultrasound characteristics in fibroma and fibrothecoma of the ovary. Ultrasound Obstet
Gynecol 2009; 34:188195.
Haider Z, Condous G, Ahmed S, Kirk E, Bourne T. Transvaginal sonographic diagnosis of appendicitis in
acute pelvic pain. J Ultrasound Med 2006; 25:12431244.
57
Page 135 of 166

The Fetal Medicine
Foundation
Early detection of congenital and chromosomal abnormalities
Petya Chaveeva
Ob/Gyn Shterev Hospital, Sofia
The Fetal Medicine

Foundation Early pregnancy
Inverting the pyramid of pregnancy care
12w
Specialist
care 12-34w 22w
32 or 36w
41w
Page 136 of 166

The Fetal Medicine
Foundation First trimester
Risk stratification in Pregnancy
12w
Specialist
care 12-34w 22w
ANEUPLOIDY
32 or 36w FETAL DEFECTS
PREECLAMPSIA
GESTATIONAL DIABETES
41w
PRETERM BIRTH
FETAL SURGERY
The Fetal Medicine

Screening for Down syndrome
Foundation
Fetal nuchal translucency
Nicolaides KH, Azar G, Byrne D, Mansur C, Marks K. Fetal nuchal

translucency:
Ultrasound screening for chromosomal defects in first trimester of
pregnancy.
BMJ 1992;304:867-9
Page 137 of 166

The Fetal Medicine Assessment of NT
Foundation
11-13+6 weeks
CRL 45-84 mm
Midsagital section
Magnification
Nutral position
Avoid amnion
Calliper on-to-on
Largest measurment

Foundation
Measuring the NT, we can find more.

1.5
Open spina bifida
Brain stem to
BSOB ratio
Early detection of 1.0

Normal
0.5
Spina bifida & DWM 0 Dand Walker malformation

45 50 55 60 65 70 75 80 85
Crown-rump length (mm)
BS
Brain stem
4th ventricle BS BSOB
Cisterna BSOB
magna
Chaoui R, Benoit B, Mitkowska-Wozniak H, Heling KS, Nicolaides KH. Assessment of intracranial translucency in
detection of spina bifida at 11-13 weeks. UOG 2009
Page 138 of 166

Foundation
Measuring the NT, we can find more.
Early detection of
Clefts
Chaoui R, Orosz G , heling KD, Heling KS, Sarut-Lopez A,Nicolaides
KH. Maxillary gap at 11-13 weeks' gestation: marker of cleft lip
and palate. UOG 2015
The Fetal Medicine Chromosomal abnormalities

Foundation
NT = Screening for aneuploidy
Page 139 of 166

The Fetal Medicine Screening for aneuploidies
Foundation
1st trimester combined test

Detection rate for
Risk 1 in:
20 Euploid FPR 5%
100
1 n 90%
90
Trisomy 21
10
80
10
0 70
0 1.0 2.0 3.0 4.0 5.0
Serum free -hCG (MoM) 60
100
50
NT (mm) Trisomy 21 8 Trisomy 21
8 n 40
1,000 Euploid
6
4 30
4
10,000 20
2
15 20 25 30 35 40 45 50 0
0 10
75 85 0 0.5 1.0 1.5
Maternal age (yrs) 45 55 65
Crown-rump length (mm) Serum PAPP-A (M0M) 0
The Fetal Medicine Screening for aneuploidies

Foundation
1st trimester combined test and additional US markers

Detection rate for FPR 3%
97%
100
%
90
80
70
60
50
40
30
20
10
Page 140 of 166

The Fetal Medicine Invasive testing
Foundation
Miscarriage from amnio / CVS
Singleton pregnancies with combined screening at 11-13 w
Expectant management
Amnio 1% Livebirth n = 33,310; Miscarriage n = 404 (1.2%)
CVS 1-2% Regression model to predict miscarriage
Variable OR 95% CI
Age (per year) 0.870 0.766-0.988
Delta nuchal translucency 1.778 1.496-2.114
Amnio 0.3-0.5% Ductus venosus: reversed a-wave 2.208 1.508-3.232
CVS 0.3-0.5% Log10 PAPP-A MoM 0.356 0.233-0.543
Miscarriage after CVS (n=2,396):

Observed 44 (1.8%), Expected 45 (95% CI 32-58)
Amnio 0.2-1.5% Akolekar R, Bower S, Flack N, Bilardo K, Nicolaides KH: Prediction of miscarriage
and stillbirth at 11-13 weeks and the contribution of chorionic villus sampling.
CVS 0.2-1.5% Prenat Diagn 2011:31:38.
The Fetal Medicine Chorionic villus sampling

Foundation
Akolekar R, Bower S, Flack N, Bilardo K, Nicolaides KH: Prediction of miscarriage and stillbirth at 11-13 weeks and the
contribution of chorionic villus sampling. Prenat Diagn 2011:31:38.
Page 141 of 166

The Fetal Medicine
Cell free DNA test
Foundation
Model of clinical implementation
100
Combined screening at 11-13 wks
90 1 in 1000
(age, fetal NT, serum -hCG & PAPP-A) 98%
Standardized detection rate (%)

80
1 in 500
70
96%
High risk Low risk 60
Intermediate risk
>1:10 <1:1000 1 in 100
50 85%
40 1 in 10
cfDNA test 70%
30
20
+ve -ve
10
0
Invasive test Nothing else 0 3 10 13 20 30
Screen positive rate (%)
Santorum M, Wright D, Syngelaki A, Karagioti N, Nicolaides KH. Accuracy of first trimester combined test in screening for trisomies 21, 18 and 13.
Ultrasound Obstet Gynecol 2016; doi 10.1002/uog.17283
The Fetal Medicine

Early diagnosis of fetal defects
Foundation
Consequences of increased NT
Cardiac defects
Major defects Lethal skeletal dysplasias
8.0 Diaphragmatic hernia
Exomphalos
45%
Nuchal translucency (mm)
7.0 Megacystis
6.0 25% Akinesia deformation sequence

Spinal muscular atrophy
5.0 20%
Treacher-Collins syndrome
4.0 10% Jarcho-Levin syndrome
Beckwith-Wiedemman syndrome
3.0 2.5% Smith-Lemli-Opitz syndrome
Zellweger syndrome
2.0 1.5% Noonan syndrome
di George syndrome
1.0 Congenital lymphedema
0 Dyserythropoietic anaemia
45 55 65 75 85 Thalassaemia-a
CRL (mm) Parvovirus B19 infection
Souka AP, Snijders RJ, Novakov A, Soares W, Nicolaides KH. Defects and syndromes in chromosomally normal fetuses with increased nuchal
translucency thickness at 10-14 weeks of gestation. Ultrasound Obstet Gynecol 1998; 11:391-400. 1082.
Page 142 of 166

The Fetal Medicine
Assessment of anatomy
Foundation
11-13 weeks
The Fetal Medicine Congenital anomalies

Foundation
Anomalis Detection Rate

Acrania
Alobar Holoprosenchephaly 100%
Exomphalos/Gastroschisis
Megacystis
Major heart defects

Limb defects 25-50%
Diaphragmatic hernia
Spina bifida
Facial clefts 5-14%
Study population 45, 000 Prevalence structural anomalies 1.1%
Page 143 of 166

The Fetal Medicine
Foundation
Major abnormalities
Syngelaki A, Chelemen T, Dagklis T, Allan L, Nicolaides KH. Challenges in the diagnosis of fetal non-chromosomal abnormalities at 11-13 weeks.
Prenat Diagn 2011; 31:90-102.
The Fetal Medicine

Foundation
Congenital heart disease
150
Prevalence (/1000)
100
100 100
Tricuspid regurgitation
50 & DV reversed a-wave
90
0
<1.5 2 3 4 5 >6 80
80
Risk of major cardiac defect (%)
NT (mm)
TR 70 75%
Detection rate (%)
60
60
DVr 50
40
40
30
20
10%
20
10
0
0 History 4CV /
Normal Doppler Markers
-2.0 0 2.0 4.0 6.0 Hyet 1999; Atzei 2004; Cheleman 2011;
Pereira 2011; Rembouskos 2011
Delta NT (mm)
Page 144 of 166

The Fetal Medicine
Assessment of fetal heart at 11-13 weeks
Foundation
Screening for complex heart anomalies
The Fetal Medicine

Foundation 1970s
Anencephaly / spina bifida
Campbell S et al: Anencephaly, early ultrasound diagnosis and active management. Lancet 1972
Campbell S et al: Ultrasound in the diagnosis of spina bifida. Lancet 1975
Rodeck CH, Campbell S. Prenatal diagnosis of neural-tube defects by ultrasound-guided fetoscopy. Lancet 1978
Wald et al: Maternal serum AFP in antenatal screening for anencephaly and spina bifida. Lancet 1977 DR 80% FPR 3%
Sphenoid bone
Brain stem Brain

Nicolaides KH, Campbell S, Gabbe SG, Guidetti R. Ultrasound screening for spina bifida 4th ventricle
cranial and cerebellar signs. Lancet 1986 Cisterna stem
magna
Chaoui R, Benoit B, Mitkowska-Wozniak H, Heling KS, Nicolaides KH. Assessment of Occipital bone
intracranial translucency in detection of spina bifida at 11-13 weeks. UOG 2009
Page 145 of 166

The Fetal Medicine
Foundation
Megacystis at 11-13 weeks
Study population: 108, 982
Prevalence: 1: 1350
Chromosomal abnormalities: 19%;
Trisomy 18 and trisomy 13
Bladder length:
7-15 (19%), resolution 90%
>15 (17%), resolution 0%
Syngelaki A, Guerra L, Ceccacci I, Efeturk T, Nicolaides KH: Impact of holoprosencephaly, exomphalos, megacystis and high NT in first
trimester screening for chromosomal abnormalities. Ultrasound Obstet Gynecol. 2016 . doi: 10.1002/uog.17286.
The Fetal Medicine

Foundation
Holoprosencephaly at 11-13 wks
Holoprosencephaly: alobar
Prevalence: 1: 2950
Trisomy 13
Syngeaki et al., 2016
Page 146 of 166

The Fetal Medicine
Foundation
Holoprosencephaly at 11-13 wks
Exomphalos
Prevalence: 1: 2950
Trisomy 18
Bowel only
CRL of 45-54.9 mm: 1 in 114
CRL of 55-64.9 mm: 1 in 953
Liver : 1 in 3 300
Resolution by 20 wks
Bowel: 90%
Liver : 0%
Syngeaki et al., 2016
The Fetal Medicine

Foundation In Summary
NT and early anomaly scan :
To confirm normal anatomy in early gestation

To detect major anomalies in early gestation
To select patients for early invasive procedure
To allow counselling and better management for
patients
Thank you
Page 147 of 166

BreakingBadNewsinan
EarlyPregnancySetting
RachelSmall,BSc(Hons)1,RM,RGN
LeadMidwifeforEarlyPregnancy&MiscarriageCare
HEFT,UK
ChairofAssociationOfEarlyPregnancyUnits
NoconflictofInterest
Page 148 of 166

LearningObjectives
HaveanunderstandingofwhatBadNewsisandits
occurrenceintheEarlyPregnancySetting
Toolstoassistyoutobreakbadnewsofapregnancy
loss
Tools/mechanismsofstayingresilientwhencarrying
outthisroledaily
DefinitionofBreakingBadNews
Badnewscanbedefinedasanynegativeinformation
thatadverselyandseriouslyaltersanindividualsviewof
theirfutureorexpectations.
(NationalInstitutesofHealth,2010)
Page 149 of 166

WhatisbadnewsinEarlyPregnancy?
Miscarriage
EctopicPregnancy
Abnormalityofbaby
Abnormalincidentalpathology
OngoingPregnancy
MultiplePregnancy
BreakingBadNewsinanEarlyPregnancyunitcanbean
everydayevent
IncidenceofBreakingbadnewsin
EarlyPregnancy
1:4firsttrimestermiscarriage
1:45congenitalanomaly
1:60ectopicpregnancy
1:100latetrimestermiscarriage
1:100womenhaveRecurrentMiscarriage
(OfficeforNationalStatistics)
Page 150 of 166

Whyhavetraining?
Disclosingbadnewsinanearlypregnancysettingis
unavoidable,itisanessentialskillforthisarea.
HealthProfessionalscanfinditstressfulandabsenceof
effectivetrainingmayleadthemtoadoptinappropriate
techniquesofbreakingbadnews
Badrolemodelscanperpetuatebadpractice
(Seamanetal,2014)
Guidance
NICE(2012)PainandBleedinginEarlyPregnancy
recommendedformaltrainingforallhealthprofessional
workinginEarlyPregnancy
GMCrecommendedenhancedcommunicationskilltraining
inundergraduatesisrequiredsince1993butthisisnot
specificallyforbreakingbadnews.
Thereisnonationalguidanceonhowtobreakbadnewsin
earlypregnancyunits,yetisitanessentialskillandlearning
comesthroughtrialanderrorandlearningonthejob.
Page 151 of 166

RiskstoPatientondoingabadjob:
Increaseanxiety/stress
Increaseinpain
Brokendownrelationshipwithhealthprofessional
Notconformingtotreatment
Confusion
Dissatisfaction,increaseincomplaints
Increaseinlitigation
Increaseinalastingimpactontheirabilitytoadaptand
adjust
(Fallowfield&Jenkins,2004)
Increasesnegativepsychosocialoutcome
1:5situationaldepression
1:10clinicaldepression
1:8ofclinicaldepressiongroupwillstillhaveit3years
on(Seamanetal,2014)
Bourneetal(2016)4:10womenreportedPTSD3
monthsafterpregnancyloss
Page 152 of 166

Toolsrequiredtodoagoodjobof
breakingbadnews
Resilience
Worth
Haveyourfacts
Showcompassion
Provideasafeenvironmentwhereyouwontbe
interrupted
Understandatthestartwhatyoupatients
understandingis
Recogniseandrespondtothepatientsemotions
Embracetheawkward
Bepreparedfortheunexpected
Assesscapacity
Speakatthepatientlanguage
Acknowledgetheirfeelings
Haveanawarenessofyourownfeelings,remember
youcannotfixthis,thingsaren'tok.
Page 153 of 166

Preparation:
Whatisknown
Ismoreinformationwanted
Warningshot
Denial
Explain
Listentoothers
Ventilation&acknowledgementoffeelings
Summary&plan
OfferAvailability
PeterKaye10StepApproach
SPIKES6stepprotocol
Settingthescene
Perceptionofwoman
Invitation
Knowledge
Empathy
Summarising
(BaileWFetal2000)
Page 154 of 166

Noonelikestogivebadnews
BreakingbadnewsintheEarlyPregnancySettingisa
demandingandexhaustingjobbutisanecessity
Stresshasbeenrecognisedasanoccupationalhazard
sincethe1950s
Observeforcompassionfatigueinyourcolleagues
andyourself(85%)(Goleman,D2015)
CompassionFatigueSymptoms
Alwaystired
Hopelessness
Noenjoymentofanyhobbies
Decreaseinproductivity
Inabilitytofocus
overinvolved
Dreadingwork
Insensitivitywithpatients
Page 155 of 166

Symptoms
Abrupt
Lackofmemory
Unabletosleep
USAstudyof73medicsreportedthat42%
indicatedthatstresstheyexperiencedingiving
badnewslastedseveralhoursupto3days
followingtheconsultation.(Ptaceketal,2001)
HowtopreventCompassionFatigue
Establishroutines
Havedowntime takeyourleave
Knowwhatmakesyouhappy
Acceptyourlimits&createprofessionalboundaries
Clarifymajorenergythieves
Valueyourself
Getsupportandperspective
Askforhelp
Page 156 of 166

Openforum,norepercussions
Makegoodchoices
Exercise
Bekindtoyourself
Supervision
Colleaguecare
Resilience
Worth
Acceptthatsuccessfuloutcomesarenotalwaysachievable.
Thankyou
anyQuestions?
Page 157 of 166

Bibliography
CongenitalAnomalyStatistics2010England&Wales,July2012
www.binocar.org
PeterKayeBreakingBadNews:A10stepApproachIAugust1995
DoctorscoulddoabetterjobofBreakingBadNews.SeamanAM,
ReutersFeb28,2014
Spikes a6stepprotocolfordeliveringBadNews BailedWT,
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The Role Ultrasound in Early Pregnancy

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The Role Ultrasound in Early Pregnancy

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What is the purpose of the course?

What is the purpose of the course?

What topics will be covered in the course?

What topics will be covered in the course?

PRECONGRESS COURSE 02

The role of ultrasound

Notes Page 159

Use of USS in Early Pregnancy

In UK only 2 routine USS examinations at

USS prior to this has become central to the

Early USS are indicated in women after

Determine number of embryos

Determine gestational age

Reassure about absence of

Positive Pregnancy Test

Intra-Uterine Ectopic Pregnancy Pregnancy of

Failing IUP EP Persistent

In the UK majority are carried out in

Safety of Early Pregnancy USS

Evidence so far suggests that USS used in

Use the lowest output power

Ultrasound exposes developing embryo to

MechanicalIndex MI MIisanonscreenindicatoroftherelativepotentialforultrasound AnMIof<1.0indicatesthateffects

ThermalIndex TI TIprovidesanindicationoftherelativepotentialforariseintissue ThehighertheTI,theshorterthe

Color Doppler and pulsed wave Doppler

M-mode can be used to insonate fetal heart

3D safe, as often leads to shorter scan

Transverse View of the Uterus

Transverse View of the Uterus

Visualisation of the Gestational Sac

Transverse View of the Uterus

Visualisation of the Gestational Sac

Assessment of Embryonic Structures

Transverse View of the Uterus

Visualisation of the Gestational Sac

Assessment of Embryonic Structures

Visualisation of the Right Ovary

Transverse View of the Uterus

Visualisation of the Gestational Sac

Assessment of Embryonic Structures

Visualisation of the Right Ovary

Visualisation of the Left Ovary

Transverse View of the Uterus

Visualisation of the Gestational Sac

Assessment of Embryonic Structures

Visualisation of the Right Ovary

Visualisation of the Left Ovary

Assessment of the Adnexa

Transverse View of the Uterus

Visualisation of the Gestational Sac

Assessment of Embryonic Structures

Visualisation of the Right Ovary

Visualisation of the Left Ovary

Assessment of the Adnexa

Inspection of the Pouch of Douglas

Transverse View of the Uterus

Visualisation of the Gestational Sac

Assessment of Embryonic Structures

Visualisation of the Right Ovary