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Home , Interstitial pregnancy, Ovarian pregnancy

3/27/2021

Introduction Ectopic • and pain are common symptoms early in pregnancy. They can occur in as many as •In the USA 25-30% of normal, viable . • Ectopic pregnancies account for 2% of all pregnancies • However, these symptoms are also common in • In 2011-2013 ruptured Eps were the reason for 2.7 % of early pregnancy failure and ectopic pregnancies. all pregnancy-related deaths and was the leading cause of hemorrhage-related mortality. • A significant number of patients with pain and spotting are facing the dilemma: is this a normal • Prevalence of EP among ED visits with first trimester pregnancy. bleeding or or both has been reported as high as 18%.

ACOG Practice Bulletin No. 191, Feb 2018

Introduction • Ectopic pregnancy is • The is the most defined as any common site accounting for > 90% pregnancy that is not • Heterotopic pregnancies are rare implanted in the cavity • After natural conception of a normal . - Rate 1:4,000 to 1:30,000 • Eg. Tubal, interstitial, • After IVF as high as 1:100 cervical, ovarian, • Risk factors for EP include abdominal or cesarean • Damaged fallopian tubes Graphic from: Cunningham FG et al. William’s scar pregnancy Cunningham FG et al. William’s 23rd ed. The MacGraw Hill Co. • Prior ectopic EP Obstetrics 23rd ed. The MacGraw Hill Co. (although is NOT REALLY • Risk after 1 EP is 10%; after ≥2 is 25% an ectopic pregnancy) • Approximate 50% have none

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The “old” ‘Classical Triad’ of Ectopic Pregnancy Ultrasound Diagnosis of Ectopic Pregnancy • Pain ± Syncope, • Studies from the 1980’s showed Surgical • Vaginal bleeding shoulder pain and • Sensitivity: TAS of 77-80% and for TVS of 88-90% evaluation • Amenorrhea shock • Recent studies have shown higher detection rates for TVS as expertise and equipment has improved. • Currently, history and physical exam alone rarely leads • Not all EP will be diagnosed using TVS, and not in one visit. to diagnosis; since most EP are diagnosed earlier in • A prospective study of 120 tubal EP found 73.9% were their course detected by TVS on the 1st scan; the rest were classified as • 1/3 women with EP have no clinical signs PUL. Most EPs were visualized on subsequent scans • 10% have no symptoms making the overall sensitivity of TVS 98.3% Kirk E et al. Hum Reprod Update 2014; 20 (2): 250–261

Sonographic Finding in Ectopic Pregnancy Ectopic Pregnancy • The hCG value above which a normal • There is no specific Ectopic Early IUP IUP should be visible by US or endometrial appearance “Discriminatory level” is ≥3500 mIU/ml* TVS GA by LMP Findings (weeks) or thickness that reliably • Progesterone Not Widely denotes an EP. Used Gestational 5 (± ½ wk) • <5ng/ml = abnormal pregnancy Sac • ~20% have intracavitary • 5-20ng/ml = equivocal fluid collection Yok sac 5.5 (± ½ wk) • >20 ng/ml = normal pregnancy • Hypoechoic area in the •By US the presence of GS in the uterus Embryo 6 (± ½ wk) endometrial cavity more essentially r/o an EP +FHR likely to be an early IUP* • Heterotopic pregnancies are rare *ACOG Practice Bulletin No. 191, Feb 2018 *Doubillet and Benson, 2010

Sonographic Finding in Tubal Ectopic Pregnancy Sonographic Finding in Tubal Ectopic Pregnancy • Eps are most commonly found in the adnexa within an • However, a TA scan may be needed to find the EP in patients imaginary triangle formed between the uterus, lateral pelvic with fibroids or other conditions that may elevate the f.tubes

wall and the ; Easily seen by TVS Ectopic Pregnancy Ectopic Pregnancy

Bladder

Bladder

Fibroid uterus Fibroid uterus

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Sonographic Finding in Tubal Ectopic Pregnancy Sonographic Finding in Tubal Ectopic Pregnancy ‘Bagel Sign’ • Is defined as a hyperechoic ring in the adnexa • Mass in the adnexa aka Lt Ovary • In fact is the gestational within the fallopian tube with ‘Bagel’ or ‘Blob’ sign the placenta and the (hyperechoic ). • Seen in ~80% of EP Bagel or Blob sign • The presence of a mass that is separate from the ovary should raise the suspicion of an EP with a reported PPV of 80%*.

*Barnhart KT et al Obstet Gynecol 2011;117; 299 Positive sliding organ sign. EP and ovary move separately

Sonographic Finding in Tubal Ectopic Pregnancy Definite Tubal Ectopic Pregnancy ‘Blob Sign’ • Is defined as an inhomogeneous mass in the adnexa • Definite EP with GS, YS and embryo is seen in • In fact is the , and blood clots about 15% cases. within the fallopian tube. Uterus Left Adnexa

Asymptomatic hCG 24 mIU/m

‘Live’ Tubal Ectopic Pregnancy an Useful Marker • An EP with positive cardiac activity is seen in about 1/3 • 70-80% EPs occur in the

EP with +FHR same side (ipsilateral) as Lt Ovary with CL the corpus luteum

Bagel or Blob sign

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Corpus Luteum ‘Ring-of-Fire’ an Useful Marker Corpus Luteum an Useful Marker • 20-30% the EP are in the contralateral ovary to the corpus • Color Doppler the ‘Ring-of- Lt Ovary with CL luteum Fire” sign can help differentiate ‘Ring-of-fire’ Hcg 2000; 1/7 between an EP and a CL Bagel or Blob sign LMP 6 wks Lt Ovary • Warning: Both the corpus luteum and the ectopic pregnancy may have peripheral blood flow. • The difference: the CL with its circular flow is INTRAOVARIAN Rt. Ovary with CL Lt EP

Hematosalpinx in tubal Differential Diagnosis of Ectopic Pregnancy ectopic Pregnancy • Corpus luteum • Rt Fallopian tube Ovarian or paratubal/paraovarian cysts • Bowel Rotating probe Rt Ovary Hematosalpinx Ectopic to image Fluid fallopian tube in Lt. ovarian cyst the long axis

Bagel or Blob sign Adding color hCG=1500 Cross section of the ovary and EP Doppler

Free Fluid in the Cul-de-Sac Free Fluid and Rupture Ectopic Pregnancy Fluid • A small amount of free • If pelvic fluid reaches the Morrison’s pouch pelvic fluid in the cul-de-sac uterine fundus or is present in (Pouch of Douglas) can the utero-vesical pouch the RUQ Fluid commonly be seen in both EP amount is significant. Liver and normal IUP. • If fluid is seen in the Morrison’s • Echogenic fluid has been reported in 28-56% of women pouch, there is serious intra- with EP* Cervix abdominal bleeding. • Rt. Kidney This does not confirm tubal • Focused Assessment by Fluid rupture, as blood may leak from the fimbriated end* Fluid Sonography for Trauma→ FAST scan** *Fleischer et al., 1990;Nyberg et al., 1991). **Scalea et al., 1999

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Treatment of Tubal Ectopic Medical & Surgical Treatment Protocols • Medical management may be offered to hemodynamically stable • Single, two-dose or fixed multiple dose patients, who have an unruptured • Trials have shown similar rates of successful resolution mass, and who do not have for the single and two-dose protocols and comparable absolute contraindications to MTX risk of adverse effects. administration. • Failure rate of 14.3% if hCG > 5000 compared to 3.7% when hCG < 5000 • Other predictors of failure: advanced GA, +FHR and rapidly

increasing hCG ACOG Practice Bulletin #193 2018 ACOG Practice Bulletin #193 2018

Treatment of Tubal Ectopic Treatment of Tubal Ectopic • Surgical management is required for unstable patients with • Laparoscopic resection tubal EP ruptured ectopic or hemoperitoneum • Laparoscopic resection tubal EP Right Fallopian tube dilated with Ectopic Pregnancy Hematosalpinx blood and clots due to EP

Fibroid uterus Bladder

Ectopic Pregnancy

Cornual Pregnancies…“The term “cornual pregnancy” is imprecise because it has been applied to 5 different types of pregnancies. Two of these are ectopic pregnancies, which by definition are pregnancies implanted outside Cornual Pregnancies the endometrial cavity, and 3 of these are intrauterine pregnancies……. Cornual pregnancy …is a descriptive term depicting a bump or mass effect on the external surface of the uterus in the cornual region… An eccentrically Uterus placed gestational sac causing this mass-effect has been termed a “cornual pregnancy.” The Term “Cornual Pregnancy” Should Be Abandoned Baltarowich OH .J Ultrasound Med 2017; 36:1081–1087

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All have been called Cornual Pregnancies Interstitial Pregnancy Ectopic • Interstitial pregnancies account for approximately 2-3% of Pregnancy in a rudimentary Interstitial pregnancy Pregnancy in rudimentary all ectopic pregnancies horn, with NO a direct horn, with a direct connection Pregnancy connection to the endometrial to the endometrial cavity • cavity Implantation is not within the Unicornuate Uterus endometrial cavity; but in the fallopian tube in the interstitial segment Intra-uterine • Resulting in a bulge in the external contour of the uterus • May result in significant morbidity & mortality if it Pregnancy implanted in a Pregnancy implanted in a Pregnancy implanted in the the horn of a bicornuate horn of a septate uterus lateral angle of the endometrial ruptures uterus cavity, most appropriately termed an “angular pregnancy,” • Risk factors: previous EP, previous , Baltarowich OH .J Ultrasound Med 2017; 36:1081–1087 uterine anomalies, induction ± IVF, and PID.

Chorionic Sac Separate from Chorionic Sac Separate from Endometrial Cavity Endometrial Cavity Endometrium • Empty uterine cavity • Color Doppler reveals rich blood flow surrounding the sac. • Chorionic sac >1 cm from lateral edge of the uterine Endometrium cavity (endometrium) • Thin (< 5mm) myometrial layer surrounding the Endometrium chorionic sac • Combined Sens 40%; Spec 90%

Timor-Tritsch IE, Monteagudo A et al Obstet Gynecol 1992;79:1044

Interstitial Line Points to the Pregnancy ‘Bulging Sign’ in Interstitial Pregnancy • Interstitial line • The developing pregnancy in the interstitial segment • Echogenic line extending from endometrium to results in bulging of the outer contour of the uterine pregnancy cavity • Sens 80%; Spec 98%* ‘Bulging sign’

Endometrium Uterus

Pregnancy Uterus Pregnancy

* Graphic from Ackerman TE et al. Radiol 1993; 189:83–87.

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Interstitial Pregnancy s/p Lt Tubal Resection for EP Summary of the Findings for IP in 3D Empty uterine cavity Lateral chorionic sac Thin myometrial layer

hCG 2,216

Ipsilateral tubal resection represents the highest risk factor for interstitial pregnancy

Treatment of Interstitial Pregnancy Treatment of Interstitial Pregnancy • Surgical management • Conservative (or watchful waiting) • Most commonly cornual resection using or • Stable patient with low or falling hCG who want to preserve fertility; but carries a risk of rupture • Non-surgical management • Multiple treatments although the optimal remains undetermined. • Local injection of KCL or MTX- • Systemic MTX single or two-dose; Success rates between 66 and 100 %* • Other uterine artery embolization, etc.. • Recent paper reported 70% success rate ; although, 16.5% (5 cases) had **. • GS diameter > 20mm was seen in all cases of failed non-surgical treatment. * Panelli D et al. Fertil Res Pract 2015;1:15 **Ben-David A et al. J Minim Invasive Gynecol 2020;27 (3): 625-632

Differential Diagnosis of Interstitial Pregnancy Sonographic Findings in Angular Pregnancy is the Angular Pregnancy Right lateral • Implantation in the lateral angle of the uterine cavity. • angle of the Angular pregnancies have unknown uterine cavity prevalence Uterotubal junction • Eccentric implantation; best • Located in the endometrial cavity in the seen in a transverse section of superior lateral aspect, just medial to the the uterus Uterus Sagittal uterotubal junction. • No intervening myometrium Endometrial • Have been classified as ectopic, nearly between the endometrial cavity ectopic, or intrauterine. Endometrial cavity cavity and the gestational sac. • Associated with poor OBS outcome* • Adequate myometrial mantle • Recent study positive outcome** surrounding the gestational Uterus transverse • 80% live-birth; 20% early pregnancy loss Graphic From internet uploaded by Akihiro Takeda sac. *Obstet Gynecol 1981:58:167 **Obstet Gynecol 2020;135:175

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Sonographic Findings in Angular Pregnancy 3D Multiplanar Findings in Angular Pregnancy • 3D coronal valuable in differentiating angular from interstitial. Sagittal plane: empty uterus Transverse plane: eccentric implantation • Endometrium surrounds the pregnancy

Coronal plane: superior lateral implantation

Picture from: J Uterus transverse Ultrasound Med 2017; Within the endometrial cavity; 36:1081–1087 endometrium all around the pregnancy

Natural Progression of “Angular” Pregnancies Cervical Pregnancies No treatment necessary as the pregnancy will • accounts for < 1% of all ectopic ‘move into the uterus’ with advancing gestation pregnancies. They implant in the cervical mucosa below the level of the internal os. • On digital examination, the cervix may be boggy and enlarged. • Classically presents with spontaneous and painless vaginal bleeding. EGA 6 4/7 wks • Risk factors: prior IUD usage, D&C as well as infertility treatment EGA 7 4/7 wks EGA 9 1/7 wks

Sonographic Finding of a Cervical Pregnancy Sonographic Finding of a Cervical Pregnancy • Uterine cavity is empty; ‘beware’ of co-existent IUP • On transabdominal • Gestational sac centrally located within the endocervical sonography the cervix Bladder appears large with a canal below the level of the internal os; with the placenta ‘ballooned’ cervical canal implanted in the anterior or posterior cervical lip External Os • Uterus has an ‘hourglass’ Internal Os appearance

• Pregnancy centrally located Empty uterine within the cervix with +FHR cavity Cervix with gestational sac Placenta

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Differential Diagnosis of Cervical Pregnancies Sonographic Finding of a Cervical Pregnancy Spontaneous in Progress

External Os 6 3/7 weeks embryonic • It may be difficult to differentiate a Empty uterine Internal Os pole with +FHR cavity cervical pregnancy from a spontaneous abortion in progress. • In an abortion in progress the GS is irregular and no FHR is seen. ‘Sliding sign’ or movement of the sac may be apparent. Color Doppler will NOT show a normal trophoblastic blood flow pattern

Cervical Pregnancy: Differential Diagnosis is CSP Sonographic Finding of a Cervical Pregnancy • The 3D coronal planes is not very helpful in differentiating No prior history of CD Prior history of CD GS anteriorly located it from CSP since their differences are very subtle GS centrally located Uterine cavity • The differences are: cervical with live IUP pregnancy is centrally located in the cervix; below the level of the internal os and above the external os Internal Os CSP • Uterine cavity is empty or not Cervical Pregnancy Cesarean scar may have co-existent IUP Pregnancy External Os

Treatment of Cervical Pregnancy Treatment of Cervical Pregnancy • Conservative (or watchful waiting) • Surgical management • Patients wishing to retain fertility; with no fetal cardiac • The most effective treatment has not been clearly activity and low hCG elucidated. • Medical • Surgical management may affect future fertility • Local injection with MTX or KCL • D&C, if performed, may result in catastrophic bleeding • Systemic MTX- single or multi-dose • Therefore should be avoided in these patients • Reported success rates for MTX between 60 and 90 %* • is reserved for unstable patients presenting • Lower success rates in pregnancies of advanced GA with CRL > with severe hemorrhage . 10 mm and + FHR, and hCG levels > 10,000 mIU/ml * • Local pressure by inflatable balloons • Single balloon (Foley) or a double balloon (cervical ripening Cook Parker LV et al. Arch Gynecol Obstet (2016) 294:19–27 catheter) ± MTX *Parker LV et al. Arch Gynecol Obstet (2016) 294:19–27

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Cesarean Scar Pregnancy (CSP) Sonographic Diagnosis of CSP Uterine Cavity

• Cesarean scar pregnancy likely accounts for ~ 1% of all • In inexperienced hands can be Bladder ectopic pregnancies*. However, the exact prevalence has challenging. not been clearly elucidated • Misdiagnosing a low intrauterine • The pregnancy implants in or on the pregnancy for a CSP, or a true CSP Cervix scar from a prior cesarean delivery for a normal IUP can have serious TAS • If a D&C is performed may result in consequences Bladder catastrophic bleeding • First look at the cervix • Is a predisposing risk factor for • Secondly, look at the uterine placenta accreta spectrum (PAS) * Not truly an ectopic since cavity- find the pregnancy • Risk factors: prior cesarean section it can result in a live-birth TVS

Sonographic Finding of a Cesarean Scar Pregnancy AJOG 2016 N= 242, 5-10 wks IUP= 185 CSP= 57 Sensitivity = 93.0% On a panoramic, longitudinal,Specificity = 98.9% sagittal view of the uterus Divide the uterus in+LR=84.5 half by an imaginary line determine the location- LR= 0.07 of the gestational sac If the GS is above it: it is If the GS is below it: suspect a mostly a normalNormal implantation IUP CSP or a cervicalCSP pregnancy. GS and embryo in/on prior CD scar Thin myometrial layer between the No fetal parts in the uterine cavity or cervix bladder and & gestational sac

Gestational sac close to the bladder and “Triangular” shaped gestational sac. anterior uterine wall Filling the ‘niche’ of the prior CD delivery AJOG. 2016 Aug 215(2):225.e1-7. doi: 10.1016/j.ajog.2016.02.028. Epub 2016 Feb 17.

Sonographic Diagnosis of CSP Sonographic Finding of a Cesarean Scar • Scanning tip Pregnancy • Small amount of urine in the bladder allows good imaging of • The 3D coronal plane is not very helpful in the bladder, myometrial placenta interphase. Empty uterine differentiating it from CxP since their cavity Bladder differences are very subtle Bladder • The differences are: CSP is located lower uterine segment

or upper cervix Internal os • Uterine cavity is empty or may have co-existent IUP

External Os

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Sonographic Finding of a Cesarean Scar Pregnancy Treatment of Cesarean Scar Pregnancy • The 3D coronal plane cesarean scar pregnancy vs cervical • Major Surgical • Laparotomy (hysterectomy or local excision). pregnancy. Uterus with IUP Empty uterine • Excision by laparoscopy, hysteroscopy or by transvaginal approach. cavity • US guided dilatation of the cervix followed by sharp or blunt curetting. • US guided suction aspiration without dilatation of the cervix. • Minimally Invasive Treatment • Local injection of MTX or KCl with or without local vasopressin. • Systemic Medication: Internal os • Single or multidose IM or IV of methotrexate (MTX) • Uterine artery embolization (UAE). • Combination of the above treatments. • Local pressure by inflatable balloons External Os • Single balloon (Foley) or a double balloon (cervical ripening Cook catheter)

Local pressure by inflatable balloons Double, cervical ripening balloon catheter ↓efficacy ↑ complications Am J Obstet Gynecol. 2016 • Sep;215(3):351. ↑efficacy Advantages: ↓ complications • Simultaneously terminates pregnancy and prevents bleeding ↑efficacy • ↓ complications Simple treatment; Minimize patient discomfort ↑efficacy ↓ complications • High success rate, low complication rate • Rare complication: EMV/AVM usually treated

by UAETimor-Tritsch & Monteagudo

Catheter

insertion *Courtesy: Dr Marcos and inflation Codoba, sequence Michigan Inserting the catheter* First anchor Inflating upper anchor balloon* balloon in the uterus

Secondly, pressure balloon opposite CSP Inflating lower pressure balloon* Adjusting balloon volumes TimorTimor-Tritsch-Tritsch & Monteagudo et al AJOG 2016

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The final image of the balloons in place with the compressed CSP Example of catheter insertion, inflation and deflation sequence Gestational sac of CSP Cx

Anchor balloon Pressure balloon

Timor-Tritsch & Monteagudo Timor-Tritsch et al AJOG 2016 This is a video clip!!!!!

Abdominal Pregnancies Sonographic Findings in Abdominal • Abdominal pregnancies are rare accounting Pregnancies for approximately for 1 % of ectopic • Empty uterus pregnancies. • No evidence of a tubal, • Classified as: cervical or ovarian ectopic • Primary, occur when fertilization of the ovum takes place within the abdominal cavity. pregnancy • Secondary, theorized to result from extrusion • Intraperitoneal gestational sac, with cardiac activity. of a pregnancy from a fallopian tube with 2ry • Most common implantation sites are anterior and implantation anywhere in the abdomen posterior cul-de-sac and on the serosa of the uterus • Associated with significant maternal morbidity and and adnexa. mortality (8X that of tubal) • ±Hemoperitoneum

Differential Diagnosis of Abdominal Pregnancies Differential Diagnosis of Abdominal Pregnancies • The GS sac is seen intraabdominally • Differentiating between an abdominal and tubal EP or a • No surrounding myometrium pregnancy in a horn of a septate or is • Placenta attached to uterine serosa or other organs difficult. Pregnancy • In a tubal EP the GS is well defined and Pregnancy typically is located lateral to the uterus • In a pregnancy in a septate or bicornuate uterus the GS is surroundedrt rt rt by thick myometrium. 3D coronal uterus uterus reveals pregnancy within the uterus Uterus CRL c/w 11 3/7wks + FHR posterior CRL c/w 11 3/7wks + FHR posterior posterior

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Ovarian Pregnancies Sonographic Diagnosis of • Rare; account for approximately 0.5-3% of all ectopic • Empty uterus pregnancies • Symptoms similar to tubal EP with rising hCG, pain st Spielberg’s Criteria for • 75% will terminate in the 1 and bleeding Ovary trimester Pathologic Dx Ovarian Pregnancy • Echogenic ring with an internal Ovary • Often misdiagnosed as a Fallopian tube on the affect side is normal anechoic area on the ovarian hemorrhagic corpus luteum GS has to be in the ovary surface • Ovary Often present as a ruptured EP GS and ovary connects to the • Ovarian cortex, including corpus • Risk factors: PID, IUD use, luteum or follicles seen around , and assisted Placenta tissue mixed with the structure Ovary reproductive technologies ovarian cortex

Differential Diagnopsis of Ovarian Pregnancy • Ovarian ectopic pregnancies must be differentiated from tubal ectopic pregnancy, hemorrhagic corpus luteum or ovarian cyst • Tubal ectopic will be seen separately from the ovary: ‘bagel or blob’ sign In summary ….. • The CL will demonstrate the typical ‘Ring- of-Fire’ blood flow pattern; irregular Kachewar SG, Sankaye SB. Ovarian margin and internal low-level fluid ectopic pregnancy: A case report. J Mahatma Gandhi Inst Med Sci • Ovarian cyst typically have a thin wall 2016;21:147-50 and clear fluid

Conclusions: • The majority of ectopic pregnancies are tubal ectopic pregnancies. • The finding of an empty uterus is an important clue to the diagnosis of ectopic pregnancies. • 3D coronal plane of the uterus is indispensable in correctly diagnosing an interstitial pregnancy • Cervical pregnancies occur in a uterus without a prior CD while all CSP have a history of a prior CD • Abdominal and ovarian pregnancies are rare

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