the article lecture goals - ucsf cme...• double decidual sac sign – specificity: 85 - 98% –...

10/22/2014

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New Recommendations for Diagnosing Failed Intrauterine Pregnancy

Lori Strachowski, MDClinical Professor of Radiology, UCSF

Chief of Ultrasound, SFGH

[email protected]

Nothing to disclose.

The Article

N Engl J Med October 2013;369:1443-51

Lecture Goals• Detailed overview of update on diagnostic criteria for

nonviable pregnancy early in the first trimester– Panelists– Issue – Objective– Plan– Recommended criteria– Reasoning

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The Panelists• Society of Radiologists in Ultrasound (SRU) Multispecialty

Panel on Early First Trimester Miscarriage and Exclusion of a Viable Intrauterine Pregnancy

• 3 Specialties:– Radiologists (7)– Obstetrician-Gynecologists (5)– Emergency Medicine (3)

The Rads

• Peter M. Doubilet, M.D., Ph.D., Brigham and Women’s and Harvard Medical School*

• Carol B. Benson, M.D., Brigham and Women’s/Harvard* • Beryl R. Benacerraf, M.D., Brigham and Women’s/Harvard• Douglas L. Brown, M.D., Mayo Clinic, Rochester• Roy A. Filly, M.D., UCSF• Edward A. Lyons, M.D., Univ of Manitoba, Winnipeg, MB• Dolores H. Pretorius, M.D., UCSD

* primary authors

The OB/Gyn’s

• Tom Bourne, M.B., B.S., Ph.D., Imperial College, London*• Steven R. Goldstein, M.D., NYU School of Medicine• Ilan E. Timor-Tritsch, M.D., NYU School of Medicine• Kurt T. Barnhart, M.D., M.S.C.E., University of Pennsylvania• Misty Blanchette Porter, M.D., Dartmouth

* primary authors

The ER Docs

• Michael Blaivas, M.D., University of South Carolina*• J. Christian Fox, M.D., University of California, Irvine• John L. Kendall, M.D., Denver Health Medical Center

* primary authors

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The Issue

www.facebook.com

Pain +/- Bleeding in Early PregnancyMisuse and misinterpretation of US and β-hCG

Methotrexate inadvertently administered

Miscarriage and malformations

MALPRACTICE_ _ _ _ _ _ _ _ _ _ _

Medical Liability Action• 2009 Survey on Professional Liability conducted by ACOG

– 90.5%: ≥ 1 professional liability claim– Avg: 2.69 claims per obstetrician - gynecologist

• 62% - OB care• 38% - Gyne care

– Delayed dx of breast cancer– Inadvertent Tx of IUPs with MTX

Obstetrics and Gynecology 2010 ;116:8-15

Inadvertent Tx of IUPs with MTX• 3 diagnostic error patterns

– Perception and interpretation of findings on US

– Improper correlation of β-hCG levels and US findings

– Treatment based on a single hCG level without a definitive US diagnosis of ectopic pregnancy


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US Error Types• Perception:

– Finding seen in retrospect but initially missed• i.e. an early intrauterine GS or YS

• Interpretation:– Findings perceived but incorrectly diagnosed

• i.e. CL interpreted as EP or early GS as a pseudo-sac• Confounding factors:

– Poor quality images, noncritical image evaluation, incomplete clinical info


The Objective

First, DO NO HARM

“or the least possible”

The Plan• Set quality standards for diagnostic tests

• Standardize terminology

• Establish diagnostic criteria – Widely applicable and reproducible– Minimize risk

• Based on consequences of false positive and negative results

The Diagnostic Tests: hCG• Human chorionic gonadotropin

– Serum measured with use of WHO 3rd or 4th International Standard

– Positive serum pregnancy test is defined by > 5 mIU/ml

NOTE: low levels of hCG can occur in health non-pregnant patients.

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The Diagnostic Tests: US • Minimum quality criteria:

– TVS of uterus and adnexa– TAS for FF and mass high in the pelvis– Oversight by an appropriately trained physician– Performed by providers and interpreted by physicians, all

of whom meet at least minimum training or certification standards

– Scanning equipment permitting adequate visualization of structures early in the first trimester

The Terminology • Viable

• Nonviable

Definition: Viable (vī-ə-bəl)1: capable of living; especially: having attained such form and development as to be normally capable of surviving outside the mother's womb <a viable fetus>

www.Merriam-Webster.com



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2: capable of growing or developing <viable seeds> <viable eggs>

3 a : capable of working, functioning, or developing adequately <viable alternatives> b : capable of existence and development as an independent unit <the colony is now a viable state> c (1) : having a reasonable chance of succeeding <a viablecandidate> (2) : financially sustainable <a viable enterprise>



2: capable of growing or developing <viable seeds> <viable eggs>

3 a : capable of working, functioning, or developing adequately <viable alternatives> b : capable of existence and development as an independent unit <the colony is now a viable state> c (1) : having a reasonable chance of succeeding <a viablecandidate> (2) : financially sustainable <a viable enterprise>


The Terminology• Viable:

– A pregnancy is viable if it can potentially result in a liveborn baby.

• Nonviable: – A pregnancy is nonviable if it cannot possibly result in a

liveborn baby. • Examples: ectopic pregnancies and failed intrauterine

pregnanciesManual uterine

aspiration

The Differential

CurrentlyViable

IUPFailed/Failing

IUP

Ectopic pregnancy

Expectant management

MUA +/- MTX +/or surgery

MUA

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Currently Viable IUP The Differential

CurrentlyViable

IUPFailed/Failing

IUP

Ectopic pregnancy



MUA

Ectopic Pregnancy

Ov

The Differential

CurrentlyViable

IUPFailed/Failing

IUP

Ectopic pregnancy



MUA

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Spontaneous AB in ProgressCervix

The Differential

CurrentlyViable

IUPFailed/Failing

IUP

Ectopic pregnancy



MUA

What is the best diagnosis for this1st trimester pregnancy?

A. B. C. D.

20%

71%

1%7%

A. Currently viable IUPB. Failed/failing IUPC. Ectopic PregnancyD. I don’t like any of these

answers

It ain’t always that easy!

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FP + FN Consequences

CurrentlyViable

IUPFailed/Failing

IUP

Ectopic pregnancy



MUA

FP: Viable IUP

Short delay in dx

FN: Failure


CurrentlyViable

IUPFailed/Failing

IUP

Ectopic pregnancy



MUAShort delay in dxLikely non-life-

threatening!

FN: EP


CurrentlyViable

IUPFailed/Failing

IUP

Ectopic pregnancy



MUAShort delay in dxLikely non-life-

threatening!

FN: EP FN: Failure


CurrentlyViable

IUPFailed/Failing

IUP

Ectopic pregnancy



MUA

FP: Failure FP: EP

Short delay in dxLikely non-life-

threatening!

FN: Viable IUP FN: Viable IUP

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To “DO NO HARM”1. Criteria for non-viability require

– 100% Specificity– 100% PPV

2. Need more buckets!!!

“or as close as possible”

The Expanded Differential

CurrentlyViable

IUPFailed/Failing

IUP

Ectopic pregnancy



MUA

IUP of Uncertain Viability

Pregnancyof

UnknownLocation


CurrentlyViable

IUPFailed/Failing

IUP

Ectopic pregnancy



MUA


Pregnancyof

UnknownLocation



The Terminology• Intrauterine pregnancy of uncertain viability:

– Transvaginal ultrasonography shows an intrauterine gestational sac with no embryonic heartbeat and no findings of definite pregnancy failure.

• Pregnancy of unknown location:– Positive pregnancy test and no intrauterine or ectopic

pregnancy on transvaginal US.

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The Pivotal Question

Is there a chance of a viable pregnancy?


CurrentlyViable

IUPFailed/Failing

IUP

Ectopic pregnancy



MUA


Pregnancyof

UnknownLocation



Viable IUP

Failure

Short delay in dx

EP

Likely non-life threatening

Short delay in dx

Viable IUP

Failure

Likely non-life threatening

EP


CurrentlyViable

IUPFailed/Failing

IUP

Ectopic pregnancy



MUA


Pregnancyof

UnknownLocation




Failed/Failing

IUPIUP of Uncertain Viability

Pregnancyof

UnknownLocation

Specific criteria and management algorithms

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Literature on Nonviable IUP Criteria• Serum beta level

– Largely unreliable given range of normal

• US findings– Size-based criteria

• Embryo without heart motion• GS without an embryo

– Time-based criteria• Appearance of interval findings

What is the correct order of appearance?

A. B. C. D.

12%

52%

34%

2%

A. Yolk sac – Gestational sac – Embryo – Amnion B. Yolk sac – Amnion – Embryo – Gestational SacC. Gestational sac – Yolk sac – Embryo – Amnion D. Gestational sac – Yolk sac – Amnion – Embryo

Let’s review normal.

vv

US of Early Pregnancy• In order of appearance:

– Intradecidual sign– Double decidual sac sign– Yolk sac– Embryo– Amnion

(+ heart motion)

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(+ heart motion)

“White Lines” of the EndometriumPost menses

B

Basalis (2 layers)

“White Lines” of the EndometriumEarly Proliferative Phase

Basalis (2 layers) Functionalis = Spongiosum and Compactum

B

BC S

S

“White Lines” of the Endometrium

B

B

C SS


Late Proliferative Phase

Aka: “Triple line sign”

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“White Lines” of the EndometriumSecretory Phase




Early Secretory Phase



Late Secretory Phase



Decidua

In Pregnancy

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Blastocyst

Decidua

In Pregnancy



In Pregnancy = DeciduaDecidua

In Pregnancy

Intradecidual Sign


In Pregnancy = DeciduaDecidua

In Pregnancy

Intradecidual Sign• ~ 3-4 weeks

• US:– ≥ 2 mm cyst– Thin echogenic rim– Eccentric to central

echogenic line – “Color flash”

• Occasionally helpful

Yeh, et.al., Radiology. 1986 Nov;161(2)

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Intradecidual Sign: Mimics• DDx:

– Intracavitary fluid– Decidual cysts

• IUP• EP

– Endometrial pathology• Polyps• Cystic hyperplasia• Malignancy

Intradecidual Sign

Grows ~ 1mm/day and becomes….

Double Decidual Sac Sign Double Decidual Sac Sign• ~ 5 weeks

• US:– Round/oval fluid

collection– 2 echogenic rims

• Inner: chorion• Outer: decidua

Bradley, Filly, et.al., Radiology.1982 Apr;143(1)

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Double Decidual Sac Sign: Mimic• Pseudo-gestational sac• DDx:

– Decidual reaction– Implantation bleed– EP (10-20%)

• US:– Fluid collection

• 1 echogenic rim• Acute ‘s, “tear -

drop” shaped

How reliable are these signs?• Intradecidual sac sign

– Specificity: 66 - 97%– Sensitivity: 48 - 92 %

• Double decidual sac sign– Specificity: 85 - 98%– Sensitivity: 64 - 95%

Absent in at least 35% of

gestational sacs

Any round/oval fluid collection = GS

“ Therefore, any round or oval fluid collection in a woman with a positive pregnancy test most likely represents an intrauterine

gestational sac and should be reported as such.”

N Engl J Med October 2013;369:1445

Mean Sac Diameter Measurement• Add dimensions of anechoic sac

(excluding echogenic rim)– Length + height + width

• Divide by 3

+ +

LONG

TRANS

Report: “If this represents a GS, the MSD measures # mm”

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Mean Sac Diameter Measurement• Add dimensions of anechoic sac

(excluding echogenic rim)– Length + height + width

• Divide by 3

+ +

LONG

TRANS

Report: “If this represents a GS, the MSD measures # mm”

Yolk Sac • ~ 5 ½ weeks

• US:– Thin round ring-like

structure– 3-5 mm

• Typically not > 6 mm

IUP MSD IUP MSD

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What do you do/say in your report/notes?

A. B. C. D.

60%

33%

7%0%

A. Too early to calculate gestational age and EDCB. Have your partner figure out interval growth when she

returns for her 18 – 20 week scanC. Measure yolk sac and add to MSDD. Use the formula MSD (mm) + 30 = GA (days) and wheel out

the EDC

IUP MSD

MSD (mm) + 30 = GA (days)i.e. 10 + 30 = 40 days (5 wks, 5 days)

Embryo • ~ 6 weeks

• US:– Flickering heart motion

adjacent to yolk sac– Grows ~ 1mm/day– Reniform, tadpole

appearance

Crown-rump length (CRL) = avg of 2-3 end-to-end measurements

Amnion• ~ 8 weeks

• US:– Very thin echogenic

membrane surrounding embryo

– Between YS and embryo – “Fuses” with chorion:

12-16 weeks

“2nd skin”

YS

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(+ heart motion)

4 criteria definitive for failure2 size based

2 time based

Discriminatory CRL• Defined as CRL size, above which, the absence of cardiac

motion is unequivocal for failure• Historically: 5 mm

– However:• Sensitivity: 50%• More recent data: 5-6 mm • Inter-observer variability: + 15%

• Most conservative scenario:Upper nl CRL (6 mm) + 15% (0.9) = 6.9 mm7.0 mm

Criteria Definitive for Failure1. CRL ≥ 7 mm without

cardiac activity – PPV for failure: 100%

“Embryonic demise”

Discriminatory MSD• Defined as MSD size, above which, the absence of an embryo

is unequivocal for failure• Historically: 16 – 18 mm

– However:• Sensitivity: 50%• More recent data = 17-21 mm• Inter-observer variability: + 19%

• Most conservative scenario:Upper nl MSD (21 mm) + 19% (4) = 25 mm

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Criteria Definitive for Failure2. MSD ≥ 25 mm and no visible

embryo– PPV for failure: 100%

“1st trimester pregnancy failure”

Time-Based Criteria for Failure• Needed as discriminatory sac or embryo sizes may never be

achieved• Based on timing of interval appearance:

– GS - 5 weeks – YS - 5 ½ weeks– Embryo with heart motion - 6 weeks

• Most conservative scenario:– Lower nl GS (4 ½ wks) - upper nl embryo (6 ½ wks) = 2 wks– Lower nl YS (5 wks) - upper nl embryo (6 ½ wks) = 1 ½ wks

+/- ½ week

11 days14 days

Criteria Definitive for Failure3. Absence of embryo with heartbeat ≥ 14 days after a scan that

showed a GS without a YS

4. Absence of embryo with heartbeat ≥ 11 days after a scan that showed a GS with a YS

8 criteria suggestive for failure

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Criteria Suggestive for Failure1. CRL <7 mm and no heartbeat

2. MSD of 16 - 24 mm and no embryo

3. Absence of embryo +HM 7–13 days after a GS without a YS

4. Absence of embryo +HM 7–10 days after a GS with a YS

“When there are findings suspicious for pregnancy failure, follow-up US at 7 to 10 days is generally appropriate.”

Do we really need to wait to call this?

Normal GS and embryo grow ~1 mm/day

Criteria Suggestive for Failure5. Empty amnion

- Amnion adjacent to YS, with no visible embryo



6. Enlarged yolk sac (>7 mm)

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6. Enlarged yolk sac (>7 mm)

7. Small GS in relation to size of embryo

- MSD – CRL = <5

Criteria Suggestive for Failure8. Absence of embryo ≥ 6 wk

after last menstrual period

CAUTION!!!- Would only consider if:

– Reliable historian with very regular cycles

OR– IVF patient

Pregnancy of Unknown Location• Defined as:

– Pregnant (serum beta hCG > 5 mIU/ml)– US findings:

• No intrauterine fluid collection• Normal (or near normal) adnexa

corpus luteum of pregnancy

Pregnancy of Unknown Location

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Pregnancy of Unknown Location• NOTE: Serum beta levels

– A single measurement of hCG, regardless of its value, does not reliably distinguish between EP and IUP (viable or nonviable)

– Discriminatory level of 2000 (to dx IUP) may not be high enough• Looked at likelihood ratios of different outcomes based

on range of serum beta hCG

Beta vs. Likely Outcome

Serum beta Likely outcome

< 2000 mIU/ml Viable IUP




2000 – 3000 mIU/mlNonviable IUP - 38:1

EP - 19:1 Viable IUP: 2%




2000 – 3000 mIU/mlNonviable IUP - 38:1

EP - 19:1 Viable IUP: 2%

> 3000 mIU/mlNonviable IUP - 140:1

EP - 70: 1Viable IUP: 0.5%

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Pregnancy of Unknown Location• Management recommendations:

– Beta hCG <3000 and stable:• Presumptive tx for EP with MTX or other pharmacologic

or surgical means should not be undertaken, in order to avoid the risk of interrupting a viable IUP.

– Beta hCG ≥3000 and stable:• A viable IUP is possible but unlikely. However, as the

most likely diagnosis is a nonviable IUP, it is generally appropriate to obtain at least one follow-up hCG and follow-up US before undertaking treatment for EP.

Pregnancy of Unknown Location• Management recommendations:

– Beta hCG <3000 and stable:• Presumptive tx for EP with MTX or other pharmacologic

or surgical means should not be undertaken, in order to avoid the risk of interrupting a viable IUP.

– Beta hCG ≥3000 and stable:• A viable IUP is possible but unlikely. However, as the

most likely diagnosis is a nonviable IUP, it is generally appropriate to obtain at least one follow-up hCG and follow-up US before undertaking treatment for EP.

Pregnancy of Unknown Location• NOTE:

– When US not yet performed:• No single serum beta level predicts the likelihood of EP

rupture. • When clinical findings are suspicious for EP, transvaginal

ultrasonography is indicated, even when the hCG level is low.

There isn’t a beta low enough to exclude EP.You gotta do the US!

The Basic Assumption• Pregnancy is desired.

UCSF: Meredith Warden, M.D., M.P.H. Jody Steinauer, M.D., Univ of Penn: Courtney A. Schreiber, M.D., M.P.H.

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In Conclusion• First, DO NO HARM to a potentially viable pregnancy

• Consider adding “IUP of Uncertain Viability” and “Pregnancy of Unknown Location” to your lexicon and manage expectantly

• In setting of PUL, stable pt. and desired pregnancy– Always get an US – Beta < 3000, f/u serial betas and US as indicated– Beta ≥ 3000, though viable IUP highly, may consider f/u

beta

and desired

Upper beta limit not addressed.

In Conclusion• Definitive criteria for early IUP failure:

– CRL ≥ 7 mm + no heart motion– MSD ≥ 25 mm and no embryo– No embryo ≥ 14 days after a GS without a YS – No embryo ≥ 11 days after a GS with a YS

• Suggestive for failure:– No embryonic heart motion– Empty amnion sign– YS too big, GS too small, others– Consider repeat US at 7-10 days

highly suggestive, in my opinion

sooner sometimes OK too , in my opinion

Role of beta?

Thank you for your attention.

the article lecture goals - ucsf cme...• double decidual sac sign – specificity: 85 - 98% –...

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