Ectopic PregnancyBrittney Bastow MD
Assistant Professor OBGYN
University of Colorado
Disclosuresnone
Objectives
• Discuss work up of pregnancy of unknown location.Discuss
• Identify patients at risk of an ectopic pregnancy.Identify
• Evaluate pelvic ultrasound for findings concerning for tubal ectopic pregnancies.
Evaluate
• Review Non‐tubal Ectopic pregnancy including interstitial pregnancy and cesarean scar.
Review
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CASEKG
34 yo G1 with RLQ pain x 3 weeks with worsening over the last 2 days presented to the ED. She had bleeding 1 week ago but lighter than her normal period.
OB‐ nulliparous
GYN‐ normal periods, no current BC, remote history of CT
PMH/PSH‐ none
Normal vitalsAbdomen soft but diffusely tender without rebound/guardingPelvic normal without CMT, uterine tenderness, adnexal masses
Work up
Beta‐hcg 3533 H/H normal GC/CT negative
Beta‐hcg and the discriminatory zonePrevious mantra
1500 for TVUS
5000 for TAUS
Discriminatory zone needs to be set conservatively high to avoid interruption of normal pregnancy‐ 3500
ACOG PB 193.
CASE
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Pregnancy of Unknown Location
Transient state and not a diagnosisClinically stable with desire to continue pregnancy > serial monitoring with ultrasound and beta hcg
Radiographic IUP is not diagnosed until gestational sac with yolk sac
At UCH‐ “quant clinic” Tuesday afternoons
Sivalingam VN. 2011.
Beta‐hcgHCG
Curvilinear increase to a plateau at about 100,000 at around 10 weeks gestationRate of rise is variable and depends on initial hcg
% change over 48 hours to diagnose IUP
35% increaseSEN 92.3%, SP 94%
53% increaseSEN 82.6%, SP 97.2%,
Morse CB. 2012
CASEDate HCG %change
8/6 3533
8/8 3760 6.4%
8/10 4466 18.8%
8/12 NO SHOW
8/19 Called‐ no answer
LOST TO FOLLOW UP 😔
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Ectopic pregnancy
Photo‐ Elsevier. Ovalle & Nahirney: Netter’s Essential Histology
Ectopic PregnancyPresentation
Vaginal bleeding and pain between 6‐10 weeks gestation
20% have shoulder pain, syncope
75% with abdominal tenderness
67% CMT
1/3 have no clinical signs, 9% with no symptomsDifferential Diagnosis
appendicitis, ruptured CL, threatened AB, torsion, UTI, TOA/PID/salpingitis
Sivalingam VN. 2011.
Risk FactorsIUD in situ
History of prior ectopic pregnancy
ART
Prior tubal damage including prior pelvic or tubal surgeries
Ascending infection including STI and PID
Tobacco use
Maternal age >35
1. Ankum WM. 19962. Barnhart KT. 20063. Sivalingam VM. 2011
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IUD and ectopicLNG IUD
Pearl Index: 0.1‐0.6 per 100 women‐years of use1
Ectopic pregnancy rate 0.02‐0.2 per 100 women‐years of use1
Up to 50% of pregnancies are ectopic2
Does not mask normal pregnancy s/s2
31 yo G4P2012 presented with +UPT and LNG IUD in place. Informal bedside clinic ultrasound with no IUP.
Hcg 7153
Normal h/h and vitals
Benign abdominal and pelvic exams
Ultrasound with…
1. Heinemann K. 20152.Backman T. 2004
IUD and ectopicLNG IUD
Pearl Index: 0.1‐0.6 per 100 women‐years of use1
Ectopic pregnancy rate 0.02‐0.2 per 100 women‐years of use1
Up to 50% of pregnancies are ectopic2
Does not mask normal pregnancy s/s2
1. Heinemann K. 20152.Backman T. 2004
IUD and ectopicCu IUD
Pearl Index: 0.1‐2.2 per 100 woman‐years of use
Ectopic pregnancy rate 0.1‐0.8 per 100 woman‐years of use
In 2/2016 a 30 yo G5P3 at unknown gestational age with Paragard IUD in place presented to the ED.
Hcg 4422
Normal h/h and normal vitals
RLQ pain but no rebound/guarding
Ultrasound with…
Heinemann K. 2015
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IUD and ectopicCu IUD
Pearl Index: 0.1‐2.2 per 100 women‐years of use
Ectopic pregnancy rate 0.1‐0.8 per 100 women‐years of use
Heinemann K. 2015
History of prior tubal ectopicReturned 5/2016 after her right salpingectomy with +UPT, cramping/LLQ pain, and spotting.
Hcg 132
Normal h/h and normal vitals
Abdominal and pelvic exam negative
Ultrasound with…
Returned 5/2016 after her right salpingectomy with +UPT, cramping, LLQ pain, and spotting.
HCG 132
Normal H/H and normal vitals
Abdominal and pelvic exam negative
Ultrasound with…
Adjusted OR 95% CI
1 prior ectopic 2.93 1.88‐4.73
2 prior ectopics 14.06 5.39‐47.72
Barnhart KT. 2006.
History of prior tubal ectopicAdjusted OR 95% CI
1 prior ectopic 2.93 1.88‐4.73
2 prior ectopics 14.06 5.39‐47.72
Barnhart KT. 2006.
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History of prior tubal ectopicMEDICAL MANAGEMENT
METHOTREXATE
No difference in AMH, future fertility or ovarian reserve1,2
Delay pregnancy at least 3 months
Detectable MTX in liver cells 116 days after injection
When compared to tubal sparing surgery – no difference in rate of EP2
SURGICAL MANAGEMENT
SALPINGOSTOMY VS SALPINGECTOMY
Recurrent ectopic pregnancy rate3, 4
Salpingostomy 6.3 – 8%
Salpingectomy 5 – 8.1%
RCT: No change in rate of subsequent IUP (RR 1.04 95% CI 0.899‐1.21) or EP (RR 1.30 95% CI 0.72‐2.38)2
Cohort: salpingostomy has increased risk of future EP (RR 2.27 95% CI 1.12‐4.58)2
1. Svirsky R. 2017 2. ACOG PB 193.3. Li J. 2015.4. Jamard A. 2016
ARTUSA Data
CDC captures 95% of all US ART data1
1.7% of all transcervical embryo transfer cycles were ectopicMost common factor associated with ectopic: TUBAL FACTOR INFERTILITY
International data2
IVF, IVF/ICSI, and IUI1.4% of all pregnancies were ectopicMost common factor associated with ectopic: TUBAL FACTOR INFERTILITY
Both internationally and in USRates of ectopic have decreased
US: 2% in 2001 (95% CI 1.9‐2.2%) versus 1.6% in 2011 (95% CI 1.5‐1.7%)International: 20.0/1000 cycles in 2000 to 11.5/1000 cycles in 2012
Reasons rates have decreasedHigher number of embryos transferred increases risk (<2 versus 3)1,2Extending embryo culture day (day 3‐4 has a higher rate versus day 5‐7)2
1. Perkins KM. 2015.2. Santos‐Ribeiro S. 2016.
Ultrasound Findings
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Ultrasound Findings for EctopicAbsence of intrauterine gestational sac
Adnexal mass
Non‐cystic adnexal mass with empty uterus‐ SEN 84‐90%, SP 94‐99%
80% on same side as CL
Echogenic area adjacent to the ovary that moves separately from it on gentle pressure
Gestational sac enclosed by a hyperechoic ring (donut or bagel sign)
US findings‐ endometriumMenstrual phase
Thin, irregular interface with myometrium
Proliferative phaseHypoechoic, straight and orderly arrangement of the glandular elements
Secretory phaseMaximal thickness and echogenicity
Small free fluid at time of ovulation
Fleisher AC. 1986
US findings‐ endometriumTrilaminar Endometrium123
Statistically significantly more likely to be EP vs IUP3
21% of EP, 4.3% of failed IUP, 7.4% of normal IUP
Thin endometriumEP 8±3.5 mm vs IUP 11.6±4.6 mm (P<0.001)1
Symptomatic women4
EP 9.56±4.87 mm vs IUP 12.12±6.0 mm
99% of EP had EMS <21 mm
100% of EP had EMS ≤25 mm
1. Yadav P. 2017.2. Yasin S. 2018.3. Col‐Madendag I. 2010.4. Seeber B. 2007.
Sensitivity Specificity PPV NPV
15.9 – 42% 80.6 – 93.9% 50 – 94% 18 – 80.5%
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US findings‐ endometriumTrilaminar Endometrium123 Thin endometrium
1. Yadav P. 2017.2. Yasin S. 2018.3. Col‐Madendag I. 2010.4. Seeber B. 2007.
US findings‐ endometriumDON’T HANG YOUR HAT ON IT!
US findings‐ simple cysts
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US findings‐ corpus luteumPost‐ovulatory cyst
1‐3 cm with thick, “crenulated” vascular wall
MIMICS: Endometrioma
TOA
Malignancy
ECTOPIC
Bonde AA. 2016
US findings‐ corpus luteum
Free fluid
CUL DE SAC MORRISON’S POUCH
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CASE: KM
21 yo G2P1 presented at 6 weeks with scant brown discharge and RLQ pain
OB‐ term VAVDGYN‐ normal periods, no current BC, remote history of CT and trichomonasPMH/PSH‐ noneSH‐ current tobacco user
Normal H/H and normal vitals
Abdomen soft with mild RLQ tenderness
Beta‐hcg 3412
CASE Images
CASE Op NoteFindings: small, anteverted uterus. Normal left tube and ovary and normal right ovary. Right fallopian tube with ectopic pregnancy. No adhesions. Normal liver, stomach.
Surgery: laparoscopic right salpingectomy
Pathology: Tubal ectopic pregnancy
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CASE Follow up
+Chlamydia and trichomonas > treated with negative test of cure
Upon return to clinic POD #21 with left adnexal pain, cervical motion tenderness and
copious vaginal discharge > treated for PID
No contraception provided‐ trying to conceive
6 months later…. Presented to the ED with +UPT and vaginal bleeding
CASE Images
Beta HCG 73,269
Interstitial PregnanciesTimor‐Tritsch Criteria (1992)
1. Empty uterine cavity
2. Chorionic sac separate from the lateral edge of the uterine cavity
3. ≤5 mm myometrium surrounding the gestational sac
88‐93% specific
40% sensitive
Ackerman (1993)
Interstitial line sign‐visualization of an echogenic line that runs from the endometrial cavity to the cornual region, abutting the interstitial mass or gestational sac
98% specific
80% sensitive
Lai S. 2017
Bourdel Criteria 2007
1. Eccentricity of the gestational sac
2. Presence of myometrial tissue that surrounds the entire gestational sac with thickness of 5 mm
3. Detection of an interstitial line sign
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Interstitial Pregnancies
CASE Follow up
To OR with REI Direct injection of ectopic with intracardiac KCL
Direct injection of Methotrexate into gestational sac and surround tissue
IM injection of Methotrexate
HCG monitored Pre‐procedure 72836
6 days later 21392
6 days later 6760
7 days later 1174
12 days later 86 >> lost to follow up
Babcock Gilbert S. 2019.
Interstitial pregnancy‐ Ultrasound
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Interstitial pregnancy‐MRI
Interstitial pregnancy‐ Intraop
CD Scar‐ Ultrasound
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Heterotopic‐ Ultrasound
CD scar‐ specimen
Take Home PointsDon’t hang your hat on the beta hcg level
Have a LOW threshold to suspect EP
Evaluate all women with early pregnancy for risk factors for EP
Look for “soft markers” for EP including: thin or trilaminar endometrium, EP on same side as corpus luteum, free fluid
Give that adnexa a gentle push to see if masses are within or separate from the ovary
If pregnancy is desired and patient is stable: watch and wait
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Questions?
ReferencesACOG Practice Bulletin. Tubal Ectopic Pregnancy. Number 193, March 2018.
Sivalingam VN, Duncan WC, Kirk E, Shephard LA, Horne AW. Diagnosis and management of ectopic pregnancy. J Fam Plann Reprod Health Care. 2011 Oct;37(4):231‐40.
Morse CB, Sammel MD, Shaunik A, Allen‐Tayler L, et al. Performance of human chorionic gonadotropin curves in women at risk for ectopic pregnancy: exceptions to the rules. Fertil Steril. 2012 Jan; 97(1):101‐6.
Ankum WM, Mol BWJ, Van der Veen F, Bossuyt PMM. Risk factors for ectopic pregnancy: a meta‐analysis. Fert Steril. 1996 June; 63(6):1093‐1099.
Barnhart KT, Sammel MD, Gracia CR, Chittans J, Hummel AC, Shaunik A. Risk factors for ectopic pregnancy in women with symptomatic first trimester pregnancies. Fert Steril. 2006 July;86(1):36‐43.
Heinemann K, Reed S, Moehner S, Do Minh T. Comparative contraceptive effectiveness of levonorgestrel‐releasing and copper intrauterine devices: the European Active Surveillance Study for Intrauterine Devices. Contraception. 2015 April; 91(4):280‐3.
Backman T, Rauramo I, Huhtala S, Koskenvuo M. Pregnancy during use of the levonorgestrel intrauterine system. AJOG. 2004 Jan; 190(1): 50‐54.
Svirsky R, Ben‐ami I, erkovitch M, Halperin R, Rozovuski U. Outcomes of conception subsequent to methotrexate treatment for an unruptured ectopic pregnancy. Int J Gynaecl Obstet. 2017 Nov; 139(2):170‐173.
Li J, Jiang K, Zhao F. Fertility outcome analysis after surgical management of tubal ectopic pregnancy: a retrospective cohort study. BMJ Open. 2015 Sep;5(9):e007339.
Jamard A, Turck M, Pham AD, Dreyfus M, Benoist G. Fertility and risk of recurrence after surgical treatment of ectopic pregnancy (EP): Salpingostomy versus salpingectomy. J Gynecol Obstet Biol Reprod (Paris).2016 Feb; 45(2);129‐38.
Perkins KM, Boulet SL, Kissin DM, Jamieson DJ. Risk of Ectopic Pregnancy Associated with Assisted Reproductive Technology in the United States, 2001‐2011. Obstet Gynecol. 2015 Jan; 125(1):70‐78.
Santos‐Ribeiro S, Tournaye H, Polyzos NP. Trends in ectopic pregnancy rates following assisted reproductive technologies in the UK: a 12‐year nationwide analysis including160 000 pregnancies. Huan Reprod. 2016 Feb; 31(2):393‐40.2.
Fleischer AC, Kalemeri GC, Entman SS. Sonographic depiction of the endometrium during normal cycles. Ultrasound med Biol. 1986 Apr, 12(4):271‐7.
Yadav P, Singla A, Sidana A, Suneja A, Vaid NB. Evaluation of sonographic endometrial patterns and endometrial thickness as predictors of ectopic pregnancy. Int J Gynaecol Obstet. 2017 Jan;136(1): 70‐75.
Yasin S, Sciaky‐Tamir Y, Mostafa E, Ohel‐Shani I, Daniel‐Spiegel E. Endometrial‐pattern in early pregnancy and correlation with ectopic pregnancy. Harefuah. 2018 Sep; 157(9):599‐603.
Col‐Madendag I, Madendag Y, Kanat‐Pektas M,Danisman N. Can sonographic endometrial pattern be an early indicator for tubal ectopic pregnancy and related tubal rupture. Arch Gynecol Obstet. 2010 Feb; 218(2):189‐94.
Seeber B, Sammel M, Zhou L, Hummel A, Barnhart KT. Endometrial stripe thickness and pregnancy outcome in first‐trimester pregnancies with bleeding, pain, or both. J Reprod Med. 2007 Sep;52(9):757‐61
Bonde AA, Korngold EK, Foster BR, Fung AW, Sohaey R, Pettersson R, etal. Radiological appearances of corpus luteum cysts and their imaging mimics. Abdom Radiol. 2016 Nov; 41(11):2270‐2282.
Lai S, Chen CP Lin CJ, Chen YN, Chen SW. An Intrauterine Gestational sac surround by thin myometrium at fundus. J Med Ultrasound. 201 Oct;25(4):255‐7.
Ackerman TE, Levi CS, Dashefsky SM, Hold SC, Lindsay DJ. Interstitial line: sonographic finding in interstitial (cornual) ectopic pregnancy. Radiology. 1993 Oct; 189(1):83‐7.
Babcock Gilbert S, Alvero RJ, Roth L, Polotsky AJ. Direct Methotrexate Injection into the Gestational Sac for Nontubal Ectopic Pregnancy: A review of efficacy and outcomes from a single institution. J Minim Invasive Gynecol. 2019 March. Epub ahead of print
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