US Ectopic - IAME 2016 · 2011-01-04 · Case Presentation ••28 y.o. G1P0 pres28 y.o. G1P0...

Ultrasound in the Evaluation of Ultrasound in the Evaluation of Ectopic Pregnancy and PULEctopic Pregnancy and PUL

James M. Shwayder, M.D., J.D.James M. Shwayder, M.D., J.D.Professor and ChairProfessor and Chair

Department of Obstetrics and Gynecology Department of Obstetrics and Gynecology University of Mississippi School of MedicineUniversity of Mississippi School of Medicine

Jackson, MississippiJackson, Mississippi

Ultrasound in the Evaluation of Ultrasound in the Evaluation of Ectopic Pregnancy and PULEctopic Pregnancy and PUL

James M. Shwayder, M.D., J.D.James M. Shwayder, M.D., J.D.

Disclosures: NoneDisclosures: None

Learning ObjectivesLearning Objectives

• Nomenclature regarding pregnancy of unknown location (PUL)

• Alternative approaches the diagnostic• Alternative approaches the diagnostic dilemma of evaluating a patient with a possible ectopic pregnancy.

• Understand the value of various diagnostic tests.

• Gain insight into the ultrasound findings in patients with an ectopic pregnancy

Consensus NomenclatureConsensus Nomenclature

1. Definite ectopic pregnancy (EP)

2 Probable EP2. Probable EP

3. PUL

4. Probable intrauterine pregnancy

5. Definite IUP

Barnhart et al. Fertil Steril 2011; 95: 857Barnhart et al. Fertil Steril 2011; 95: 857--866 866


• Definite ectopic pregnancy (EP)– Extrauterine gestational sac with yolk sac

and/or embryo (with or without cardiacand/or embryo (with or without cardiac activity)

• Probable EP– Inhomogeneous adnexal mass or

extrauterine sac-like structure



• Probable intrauterine pregnancy– Intrauterine echogenic sac-like structure

• Definite IUP– Intrauterine gestational sac with yolk sac

and/or embryo (with or without cardiac activity)



• PUL– no signs of either EP or IUP


Pregnancy of Unknown LocationPregnancy of Unknown Location


Case PresentationCase Presentation

•• 28 y.o. G1P0 presents with pelvic pain 28 y.o. G1P0 presents with pelvic pain and scant vaginal spotting.and scant vaginal spotting.

•• LMP ~ 4LMP ~ 4--5 weeks ago5 weeks ago

CP 1CP 1

•• + UPT at home+ UPT at home

•• Exam:Exam: VSSVSS

Uterus AV, NT, TNSUterus AV, NT, TNS

Adnexa: NT, without massesAdnexa: NT, without masses

•• hCG = 874 IU/LhCG = 874 IU/L

Increase in hCG in early pregnancyIncrease in hCG in early pregnancy

Sampling IntervalSampling Interval (days)(days) % Increase% Increase11 292922 666622 666633 11411444 17517555 255255

Kadar et. al. Obstet Gynecol 1981; 58: 162 (Yale)Kadar et. al. Obstet Gynecol 1981; 58: 162 (Yale)


•• Doubling time = 2.98 daysDoubling time = 2.98 days

•• 15% of normal pregnancies15% of normal pregnancies•• 15% of normal pregnancies 15% of normal pregnancies had abnormal ßhad abnormal ß--hCG hCG increasesincreases

Kadar et. al. Obstet Gynecol 1981; 58: 162 (Yale)Kadar et. al. Obstet Gynecol 1981; 58: 162 (Yale)


DaysDays RangeRange MedianMedian

1 1.24 – 1.81 1.50

2 1 53 3 28 2 242 1.53 – 3.28 2.24

3 1.88 – 5.94 3.35

4 2.33 – 10.76 5.00

7 4.38 – 63.88 16.73

Barnhart et al. Obstet Gynecol 2004; 104: 50Barnhart et al. Obstet Gynecol 2004; 104: 50--55.55.


Day 1 Day 1 hCG = 874 IU/mlhCG = 874 IU/ml

D 3D 3 hCG 1 056 IU/ lhCG 1 056 IU/ l

CP 1CP 1

Day 3Day 3 hCG = 1,056 IU/mlhCG = 1,056 IU/ml

Day 5Day 5 hCG = 1,110 IU/mlhCG = 1,110 IU/ml

Threshold vs. Discriminatory LevelsThreshold vs. Discriminatory Levels

Threshold level Threshold level

•• Lowest ßLowest ß--hCG level at which a normal hCG level at which a normal intrauterine pregnancy can be detectedintrauterine pregnancy can be detected

Discriminatory level Discriminatory level

•• The level of ßThe level of ß--hCG above which all normal hCG above which all normal intrauterine pregnancies should be seenintrauterine pregnancies should be seen

Threshold vs. Discriminatory LevelsThreshold vs. Discriminatory Levels

Threshold level Threshold level

•• ßß--hCG = 400hCG = 400--500 mIU/mL (1500 mIU/mL (1stst IRP)IRP)

Discriminatory level Discriminatory level

•• ßß--hCG = 1000hCG = 1000--1500 mIU/mL (1st IRP)1500 mIU/mL (1st IRP)

DependenciesDependencies

•• Transducer frequency, uterine position, Transducer frequency, uterine position, body habitus, operator experience/abilitybody habitus, operator experience/ability

Evidence Against the Evidence Against the hCG Discriminatory LevelhCG Discriminatory Level

•• January 1, 2000 January 1, 2000 -- December 31, 2010December 31, 2010

•• TVS andTVS and ββ hCG on same dayhCG on same day•• TVS and TVS and ββ--hCG on same dayhCG on same day

•• No intrauterine fluid collectionNo intrauterine fluid collection

•• Subsequent embryonic or fetal cardiac Subsequent embryonic or fetal cardiac activityactivity

Doubilet and Benson, J Ultrasound Med 2011; 30:1637Doubilet and Benson, J Ultrasound Med 2011; 30:1637--1642 1642

Evidence Against the Evidence Against the hCG Discriminatory LevelhCG Discriminatory Level

hCG hCG (3(3--44thth IS)IS) # # (202)(202) %%

<1000 162 80.2

Doubilet and Benson, J Ultrasound Med 2011; 30:1637Doubilet and Benson, J Ultrasound Med 2011; 30:1637--1642 1642

1000-1499 19 9.4

1500-1999 12 5.9

2000 9 4.5

Reevaluation of Discriminatory Reevaluation of Discriminatory and Threshold Levels and Threshold Levels

•• 651 patients651 patients

•• TVS and TVS and ββ--hCG within 6 hours of each hCG within 6 hours of each otherotherotherother

•• Known intrauterine pregnanciesKnown intrauterine pregnancies

•• Findings visualized 99% of the timeFindings visualized 99% of the time

•• 11stst, 3, 3rdrd, or 4, or 4thth International StandardInternational Standard

–– 22ndnd I.S.~ ½ that of othersI.S.~ ½ that of others

Connolly et al. Obstet Gynecol 2013;121:65Connolly et al. Obstet Gynecol 2013;121:65--70.70.


hCG = mIU/mLhCG = mIU/mLGestationalGestational

SacSacYolk Yolk SacSac

EmbryoEmbryo

Threshold level 390 1094 1394

Discriminatorylevel

3510 17,716 47,685





•• TVSTVS–– UterusUterus

•• No evidence of IUPNo evidence of IUP

CP 1CP 1

–– OvariesOvaries•• Corpus luteum Corpus luteum -- leftleft

–– AdnexaAdnexa•• No definite adnexal pathologyNo definite adnexal pathology

•• Current terminologyCurrent terminology PULPUL•• TreatmentTreatment MTX 50 mg/mMTX 50 mg/m22


•• 24 y.o. G2P0010 presents with scant 24 y.o. G2P0010 presents with scant vaginal spotting and painvaginal spotting and pain

•• LMP ~ 5 weeks agoLMP ~ 5 weeks ago•• LMP ~ 5 weeks agoLMP ~ 5 weeks ago


Uterus NSSC, NT; Adnexa: NTUterus NSSC, NT; Adnexa: NT

•• Initial:Initial: hCG = 710 IU/LhCG = 710 IU/L

•• Repeat in 2 days: hCG = 980 IU/LRepeat in 2 days: hCG = 980 IU/L

7 4 mm7 4 mm7.4 mm7.4 mm

Endometrial Thickness in Ectopic Pregnancy Endometrial Thickness in Ectopic Pregnancy when hCG < Discriminatory Zonewhen hCG < Discriminatory Zone

OutcomeOutcomeMean Mean (mm)(mm)

Range Range (mm)(mm)

Intrauterine pregnancy 13.42 + 0.68p g y

Spontaneous abortion 9.28 + 0.88

Ectopic pregnancy 5.95 + 0.35

Abnormal pregnancy (97%) < 8

Spandorfer and Barnhart. Fertil Steril 1996; 474Spandorfer and Barnhart. Fertil Steril 1996; 474--47.47.

Case Presentation Case Presentation -- #3#3

•• 28 y.o. G1P0 presents with pelvic pain 28 y.o. G1P0 presents with pelvic pain and scant vaginal spotting.and scant vaginal spotting.

•• LMP ~ 7 weeks agoLMP ~ 7 weeks ago•• LMP ~ 7 weeks agoLMP ~ 7 weeks ago


Uterus TNS; Uterus TNS;

Mild adnexal discomfortMild adnexal discomfort

•• hCG = 4,634 IU/LhCG = 4,634 IU/L

Intrauterine Fluid with Intrauterine Fluid with Ectopic PregnancyEctopic Pregnancy

229 patients with ectopic229 patients with ectopic ## %%

•• No intrauterine fluidNo intrauterine fluid 191191 83.483.4

•• Intrauterine fluidIntrauterine fluid 3838 16.616.6–– Adnexal massAdnexal mass 3333 86.886.8

Benson et al. J Ultrasound Med 2013;32:389Benson et al. J Ultrasound Med 2013;32:389--393.393.

Intrauterine Fluid with Intrauterine Fluid with Ectopic PregnancyEctopic Pregnancy

38 patients38 patients ## %%

•• Type AType A 3131 81.681.6–– Pointy edgedPointy edged 3030 78 978 9Pointy edgedPointy edged 3030 78.978.9–– EchoesEchoes 2828 73.773.7

–– Located with the cavityLocated with the cavity 2121 55.355.3

•• Type BType B 77 18.418.4–– Smooth walled Smooth walled

–– Located in decidua or uncertainLocated in decidua or uncertain


Pointed edgePointed edge Echoes or debrisEchoes or debris

Within the uterine cavityWithin the uterine cavityBenson et al. J Ultrasound Med 2013;32:389Benson et al. J Ultrasound Med 2013;32:389--393.393.

Type AType A

Type BType B


Ectopic PregnancyEctopic Pregnancy Intrauterine PregnancyIntrauterine Pregnancy

ConclusionsConclusions

•• FindingsFindings–– A smoothA smooth--walled anechoic intrauterine walled anechoic intrauterine

cystic structurecystic structurecystic structure cystic structure

–– No adnexal mass No adnexal mass

•• ProbabilityProbability–– Intrauterine pregnancyIntrauterine pregnancy 99.8%99.8%

–– Ectopic pregnancyEctopic pregnancy 0.02%0.02%

TVS for Diagnosing EctopicsTVS for Diagnosing Ectopics

Reviewed 10 studiesReviewed 10 studies

•• 2216 patients2216 patients

*

pp

•• Ectopic = Ectopic = 565565 25.5%25.5%

•• No ectopic = 1651No ectopic = 1651 74.5%74.5%

Brown and Doubilet, J Ultrasound Med 1994; 13: 259 Brown and Doubilet, J Ultrasound Med 1994; 13: 259 (Harvard)(Harvard)


Inclusion criteriaInclusion criteria

•• Clinical suspicion of ectopic pregnancyClinical suspicion of ectopic pregnancy

•• All patients underwent TVSAll patients underwent TVSpa e s u de e Spa e s u de e S

•• All cases of EP were surgically confirmedAll cases of EP were surgically confirmed

•• No adnexal masses were excluded, except No adnexal masses were excluded, except simple cystssimple cysts

Brown and Doubilet, J Ultrasound Med 1994; 13: 259 Brown and Doubilet, J Ultrasound Med 1994; 13: 259 (Harvard)(Harvard)


Criteria for ectopic pregnancyCriteria for ectopic pregnancy

A:A: Adnexal embryo with heartbeatAdnexal embryo with heartbeat

B:B: Adnexal mass containing yolk sac or Adnexal mass containing yolk sac or embryoembryoembryoembryo

C:C: Adnexal mass with central anechoic area Adnexal mass with central anechoic area and hyperechoic rim (“tubal ring”) and hyperechoic rim (“tubal ring”)

D:D: Any adnexal mass other than a simple Any adnexal mass other than a simple cyst or an intraovarian lesioncyst or an intraovarian lesion

Brown and Doubilet, J Ultrasound Med 1994; 13: 259Brown and Doubilet, J Ultrasound Med 1994; 13: 259

TVS Criteria for Ectopic PregnancyTVS Criteria for Ectopic Pregnancy

Adnexal FindingsAdnexal Findings

TVS FindingTVS FindingLikelihood of Likelihood of

EctopicEctopic

Extrauterine embryo + heartbeat

100%

Brown and Doubilet, J Ultrasound Med 1994; 13: 259Brown and Doubilet, J Ultrasound Med 1994; 13: 259

Adnexal mass with yolk sac

or embryo without heartbeat100%

Tubal ring 95%

Complex or solid adnexal mass

No tubal ring, yolk sac, embryo92%

100%100%

Embryo without cardiac activityEmbryo without cardiac activity

Adnexal mass with yolk sac (100%)Adnexal mass with yolk sac (100%)

95%

Tubal ring (95%)

95%95%

Tubal ring (95%)Tubal ring (95%)

OVARYOVARYOVARYOVARY

MASSMASSMASSMASS

92%92%

Diagnosing Ectopic PregnancyDiagnosing Ectopic PregnancySix StrategiesSix Strategies

•• Ultrasound followed by quantitative hCGUltrasound followed by quantitative hCG•• Quantitative hCG followed by ultrasoundQuantitative hCG followed by ultrasound•• Progesterone followed by ultrasound and Progesterone followed by ultrasound and

quantitative hCGquantitative hCG•• Progesterone followed by quantitative hCG Progesterone followed by quantitative hCG

and ultrasoundand ultrasound•• Ultrasound followed by repeat ultrasoundUltrasound followed by repeat ultrasound•• Clinical examinationClinical examination

Garcia and Barnhart. Obstet Gynecol 2001; 97: 464Garcia and Barnhart. Obstet Gynecol 2001; 97: 464--70 70 (U. of Penn)(U. of Penn)

StrategyStrategy Missed Missed EP/10,000EP/10,000

Interrupted Interrupted IUP/10,000IUP/10,000

US hCG 00 7070

Diagnosing Ectopic PregnancyDiagnosing Ectopic PregnancySix StrategiesSix Strategies--OutcomesOutcomes

hCG US 00 122122

P US hCG 2424 2525

P hCG US 2424 3939

US US 00 121121

Clinical Exam 940940 00

Garcia and Barnhart. Obstet Gynecol 2001; 97: 464Garcia and Barnhart. Obstet Gynecol 2001; 97: 464--7070

Diagnosing Ectopic PregnancyDiagnosing Ectopic PregnancySix StrategiesSix Strategies--RecommendationsRecommendations

• Ultrasound followed by hCG• hCG followed by ultrasound

Eith t t l• Either progesterone protocol– More missed ectopic pregnancies

• Ultrasound followed by repeat ultrasound– May be applicable in poorly compliant patient

• Clinical exam only – NOT recommended

Garcia and Barnhart. Obstet Gynecol 2001; 97: 464Garcia and Barnhart. Obstet Gynecol 2001; 97: 464--7070


•• 41 G2P0010 with LMP 3 weeks ago41 G2P0010 with LMP 3 weeks ago

•• c/o vaginal bleeding and abdominal c/o vaginal bleeding and abdominal painpainpainpain

•• Unprotected intercourse x 10 yearsUnprotected intercourse x 10 years

•• + UCG+ UCG

Quantitative hCG = 78Quantitative hCG = 78

hCG Dynamics with Spontaneous hCG Dynamics with Spontaneous Resolution of Ectopic Resolution of Ectopic

Helsinki, FinlandHelsinki, Finland118 patients118 patientsEntry criteriaEntry criteria

Ectopic PregnancyEctopic Pregnancy

Entry criteriaEntry criteria–– Decreasing or stable hCGDecreasing or stable hCG–– No signs of rupture/intraperitoneal hemorrhageNo signs of rupture/intraperitoneal hemorrhage–– Adnexal mass < 4 cmAdnexal mass < 4 cm–– No cardiac activityNo cardiac activity

Korhonen, Stenman, Ylostalo. Fertil Steril 1994; 61: 632Korhonen, Stenman, Ylostalo. Fertil Steril 1994; 61: 632--36 36 (Finland)(Finland)


Helsinki, FinlandHelsinki, Finland•• TVS q 1TVS q 1--3 days3 days•• Serial hCG until < 10 IU/L (3Serial hCG until < 10 IU/L (3rdrd IS)IS)


•• Serial hCG until < 10 IU/L (3Serial hCG until < 10 IU/L (3 IS)IS)•• LaparoscopyLaparoscopy

–– Increasing hCG levelsIncreasing hCG levels–– Increasing abdominal painIncreasing abdominal pain–– IntraIntra--abdominal hemorrhage on TVSabdominal hemorrhage on TVS

Korhonen, Stenman, Ylostalo. Fertil Steril 1994; 61: 632Korhonen, Stenman, Ylostalo. Fertil Steril 1994; 61: 632--3636


Rate of Spontaneous ResolutionRate of Spontaneous Resolution


hCG < 200 IU/LhCG < 200 IU/L 88%88%

hCG > 2000 IU/LhCG > 2000 IU/L 25%25%

Korhonen, Stenman, Ylostalo. Fertil Steril 1994; 61: 632Korhonen, Stenman, Ylostalo. Fertil Steril 1994; 61: 632--3636

Initial hCGInitial hCG

3000

3500

4000

4500

0

500

1000

1500

2000

2500

3000


•• 36 y.o. G3P0020 seen in ER with c/o 36 y.o. G3P0020 seen in ER with c/o slight spotting and mild abdominal slight spotting and mild abdominal discomfortdiscomfort

•• Uterus: MidUterus: Mid--position, TNSposition, TNS

•• Adnexa: No definite massesAdnexa: No definite masses

•• hCG = 357 IU/LhCG = 357 IU/L

•• Hct = 36.4Hct = 36.4

•• D/C home with F/U 2 days in WCCD/C home with F/U 2 days in WCC


•• WCCWCC–– c/o increasing pain and weaknessc/o increasing pain and weakness

BLOODBLOOD

hCG = 465 IU/L

hCG = 465 IU/LhCG = 465 IU/L Serum hCG and Tubal RuptureSerum hCG and Tubal Rupture

ßß--hCG (IU/L)hCG (IU/L) UnrupturedUnruptured RupturedRuptured

< 100< 100 9.2%9.2% 11.4%11.4%

100 100 –– 999999 47.3%47.3% 38.6%38.6%

1000 1000 -- 9,9999,999 38.2%38.2% 38.6%38.6%

> 10,000> 10,000 5.3%5.3% 11.4%11.4%

Saxon et al. Obstet Gynecol 1997; 90: 46 Saxon et al. Obstet Gynecol 1997; 90: 46 (McGill, Cleveland Clinic)(McGill, Cleveland Clinic)

Serum hCG and Tubal RuptureSerum hCG and Tubal Rupture

hCG, mIU/mLhCG, mIU/mL UnrupturedUnruptured RuptureRuptureddRupture RateRupture Rate

%%

< 1000 53 14 (41.2%) 20.9

Frates et al. J Ultrasound Med 2014; 33:697Frates et al. J Ultrasound Med 2014; 33:697--703.703.

1000-1999 14 6 (17.6%) 30.0

> 2000 38 14 (41.2%) 26.9

Case presentationCase presentation

•• 28 y.o. G2P001028 y.o. G2P0010

P t ith l i i d i lP t ith l i i d i l•• Presents with pelvic pain and vaginal Presents with pelvic pain and vaginal spottingspotting

•• LMP = 7 weeks agoLMP = 7 weeks ago

•• hCG: positivehCG: positive

Courtesy of William W. Brown, III, M.D.

Ultrasound Diagnosis of Ultrasound Diagnosis of Interstitial PregnancyInterstitial Pregnancy

•• Empty uterine cavityEmpty uterine cavity

•• Chorionic sac > 1 cm Chorionic sac > 1 cm from the lateral edge from the lateral edge ggof the uterine cavity of the uterine cavity (endometrium)(endometrium)

•• Thin (<5 mm) layer of Thin (<5 mm) layer of myometrium myometrium surrounding the surrounding the chorionic sacchorionic sac

Timor et al. Obstet Gynecol 1992;79:1044 Timor et al. Obstet Gynecol 1992;79:1044

TerminologyTerminology

•• Interstitial pregnancyInterstitial pregnancy–– Embryo implants in the interstitial or intramural Embryo implants in the interstitial or intramural

portion of the Fallopian tubeportion of the Fallopian tube

•• Cornual pregnancyCornual pregnancy–– Pregnancies that occur in a rudimentary horn, Pregnancies that occur in a rudimentary horn,

unicornuate uterus, cornual region of a septate unicornuate uterus, cornual region of a septate uterus, a bicornuate uterus, or a uterus didelphysuterus, a bicornuate uterus, or a uterus didelphys

•• Angular pregnancyAngular pregnancy–– Embryo implants in one of the lateral angles of the Embryo implants in one of the lateral angles of the

uterine cavity, medial to the uterouterine cavity, medial to the utero--tubal junctiontubal junction


•• 23 y.o. G2P100123 y.o. G2P1001

E t / li ht tti d iE t / li ht tti d i•• Enters c/o slight spotting and crampingEnters c/o slight spotting and cramping

•• LMP = UnknownLMP = Unknown

•• UCG = positiveUCG = positive

•• hCG = 2,392hCG = 2,392

12/30/10

hCG = 2392

ET = 17.84 mm

12/30/10

hCG = 2392

ET = 17.84 mm


• Pregnancy of unknown location (PUL)Pregnancy of unknown location (PUL)

– Possible IUP

• Increased endometrial thickness


Quantitative hCGQuantitative hCG

12/30/1012/30/10 23922392

1/01/111/01/11 77217721

1/01/111/01/11

hCG = 7721hCG = 7721

01/01/11 01/04/11

hCG = 16,371hCG = 16,371

01/18/11

FHR = 140 bpmFHR = 140 bpm

Ectopic PregnancyEctopic Pregnancy--SummarySummary

•• Ultrasound can be justified prior to obtaining Ultrasound can be justified prior to obtaining a quantitative hCGa quantitative hCG

~ 50% of ruptured ectopics had hCG levels ~ 50% of ruptured ectopics had hCG levels below the discriminatory zone (<1000 IU)below the discriminatory zone (<1000 IU)

•• Endometrial thickness when hCG < Endometrial thickness when hCG < discriminatory leveldiscriminatory level

•• An endometrial thickness An endometrial thickness << 8 mm is 8 mm is associated with an abnormal pregnancy associated with an abnormal pregnancy 97% of the time97% of the time


•• The discriminatory level has changedThe discriminatory level has changed

•• It may be as high as 2500It may be as high as 2500--3500 IU/L3500 IU/LIt may be as high as 2500It may be as high as 2500 3500 IU/L3500 IU/L

•• A cystic structure within the endometrium, A cystic structure within the endometrium, in the absence of an adnexal massin the absence of an adnexal mass

•• Is associated with an IUP in > 99% of Is associated with an IUP in > 99% of patientspatients


•• Finding an IUP r/o ectopic pregnancyFinding an IUP r/o ectopic pregnancy•• Exception: heterotopic pregnancy Exception: heterotopic pregnancy

•• (1:667(1:667--1:30,000)1:30,000)•• Finding of embryo Finding of embryo ++ heart beat or yolk sac heart beat or yolk sac

in adnexain adnexa•• Diagnostic of ectopic pregnancyDiagnostic of ectopic pregnancy

•• No IUP. Complex/solid mass, sep from No IUP. Complex/solid mass, sep from ovaryovary•• 92% likelihood of ectopic92% likelihood of ectopic

Thank You

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