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Can we predict the behavior of a desired CSP? Over the Scar? Into the Scar/niche?

Can we link US features to prognosis yet?

Ilan E Timor-Tritsch MD

New York University Department of OB/Gyn

26th Annual Advanced US for the Practicing Ob/Gyn 2017

Cesarean Scar Pregnancy: Update 2017

I have no conflicts of interest

Cesarean Rates (per 1,000 births),

Industrialized Countries,1990-2004

50

100

150

200

250

300

350

400

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

Italy

U.S.

Germany

Netherlands

Denmark

UK

Source: OECD Health Data 2006

AbnornallyImplanted Placenta

1994-2002: 1 in 2000-2500

0.8 /1000

3 /1000

SMFM Clinical Opinion. Placenta accreta. Am J Obstet Gynecol 2010; 203:430–9.

• True incidence is not known

• ≈1 in 2000-2500 cesarean deliveries

• Rate closely related C/D rates

• 52% of CSPs had only one prior C/D

• The more previous C/D, the more CSP, the more placenta previa and accreta

Rotas MA et al, Obstet Gynecol 2006; 107: 1373-7.Jurkovic D et al, Obstet Gynecol 2003; 21: 220-7. Lin EP et et al, RadioGraphics 2008; 28:1661–1671Wu S et al, Am J Obstet Gynecol 2005;192:1458-61Miller DA et al, Am J Obstet gynecol 1997; 177:210

CSP is a man made disease

Timor-Tritsch & Monteagudo

P l a c e n t a a c c r e t a or C/S scar pregnancy

Histological slide: courtesy:of Dr. Mittal, Dept Path NYU

Let us examine the faulty implantation in a more detailed

fashion

What is the trophoblast and what does it accomplish?

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Trophoblasts (from Greek trephein: to feed, and blastos: germinator) are cells forming the outer layer of a

blastocyst, which provide nutrients to the embryo develop into a large part of the placenta. They are formed during

the first stage of pregnancy and are the first cells to differentiate from the fertilized egg

Sequence of events after fertilization

• Normal implantation involves invasion of the uterine wall by two subgroups of extravilloustrophoblast:

- the interstitial trophoblast invades through the endometrium and the superficial one-third of the myometrium.

- the endovascular trophoblast invades and remodels the maternal spiral arterioles *.

The Extravillous Trophoblasts appear, differentiate and start invading the decidua

*Tantbirojn et al, Placenta 2008; 29:639

In early pregnancy, trophoblast cells invade the the uterus, where they transform spiral arteries to ensure the enhanced delivery of

blood to the developing fetus at a low pressure

Carolin Melati OefnerResearch Email: cmo35@cam.ac.uk

E. Jauniaux, D. Jurkovic / Placenta 33 (2012) 244e251Fetomaternal immune cross-talk and its consequences for maternal and offspring's healthPetra C Arck & Kurt Hecher Nature Medicine 2013

N I t a b u c h’s F i b r I n o I d L a y e r

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• Propose that the extent of uterine wall ‘‘invasion’’ by placental villi (and resulting accreta vs. increta and percreta) may be dependent on the depth of the scar.

And that “placenta increta and percreta are not due to a further invasion of extravillous trophoblast in the uterine wall, rather they likely arise secondary to

dehiscence of a scar, leading to the presence of

chorionic villi deep within the uterine wall, and thus give extravillous trophoblast greater access to the deep myometrium”.

Is there an entity, such as placenta accreta/percreta in the

1st ∆ of the pregnancy?

• In the 1st trimester placental invasion can be identified if the sac is implanted in the anterior lower uterine segment*and suggests the possibility of placenta accreta.

*Comstock CH, Lee W, IM Vettraino , RiA Bronsteen; The Early SonographicAppearance of Placenta Accreta. Ultrasound Med 2003; 22:19–23

7w3d

Cx

Is there an entity, such as placenta accreta/percreta in the

2nd ∆ of the pregnancy?

*Comstock CH et al, Sonographic detection of placenta accreta in the second and third trimesters of pregnancy. AJOG 2004;190: 1135–40.**Timor-Trisch IE, Monteagudo A, Santos R, Tsymbal T, Pineda G, Arslan AA. The diagnosis, treatment and follow-up of cesarean scar pregnancy. AJO G 2012;207:44. e1–13.

Image at 14weeks.

Ruptured several weeks later.

Histology: Percreta

• In the early 2nd trimester US findings may be seen as early as 13-18 weeks**

In the second trimester there is high risk for complications

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Bl

Bl

15w2d

Bl

17w 2d 20 w

9w2d

6

Bl

Ilan Timor-Tritsch and Anthony Vintzileos MD Courtesy Dr Anthony Vintzileos

17 weeks. C/S x3. Placenta previa, placenta percreta, large fundal hematoma.

Courtesy Dr Mark Rebolo NYU Ob/Gyn Resident

Therefore the answer to the two questions is: YES! Placenta accreta and percreta can occur

in the 1st and early 2nd trimester

These observations are based upon:

• -- Reports of massive hemorrhage during D&C

• -- Histology of MAP in the involved uteri*

• -- Reports of proven 1st ∆ US and subsequent histology of MAP in the near term placenta

--Wolcot RJ et al 1987; Ecker JL et al 1992; Walter AJ et al 1999; Gherman RB et al 1999--Comstock CH et al . JUM 2003--Ballas J et al . JUM 2012--Timor-Trisch IE, Monteagudo A, Santos R, Tsymbal T, Pineda G, Arslan AA. The diagnosis, treatment and follow-up of cesarean scar pregnancy. AJO G 2012;207:44. --Timor-Tritsch & Monteagudo

• CSP is a precursor of MAP,

• There is now ample evidence that can be used to counsel patients with CSP, to enable them to make an informed choice between a 1st∆ TOP and continuation of the pregnancy, with its risk of premature delivery and loss of uterus and fertility.

• The question is: how accurate can we be?

The conclusion in the literature is that :

Timor-Tritsch, Monteagudo, Cali et al UOG 2014

Additional literature support for the fact that CSP is one of the precursors of placenta accreta

:46:367-375

Timor-Tritsch & Monteagudo

J Ultrasound Med 2016; 35:263–269 |

• Ten patient with CSP progressed to attempt delivery of a live neonat

• 9 succeeded

• All then had hysterectomies

• All ten had AIP

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Over the last several years it became obvious, that not all CSPs

resulted in MAP • Ten patients diagnosed with CSP

• All ten delivered live neonates

• Only 5 resulted in MAP leading to hysterectomy

The next question is: can we predict which CSPs will become MAP and

which will not

And if we can predict MAP, at what point (GA) can we diagnose

a placenta that will be pathologically adherent

First: the correct diagnosis has to be established

• Use mainly high frequency TVS!

• Transabdominal US may help

• Contrary to all the publications of using MRI, please disregard them and trust your transvaginal US!

“3. Triangular” shaped gestational sac*

1. No fetal parts in the uterine cavity or cervix 2. Thin myometrial layer between the bladder and & gestational sac

4. Gestational sac close to the bladder and anterior uterine wall

5. Rarely: A-V malformation at the site of a CS

Step 1A: For the correct diagnosis apply the sonodefinition of scar pregnancy

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Step 1B. For the correct diagnosis determine the location of the gestational

sac in the uterus

If the gestational sac is below it: suspect a CSP or a cervical

pregnancy. Counsel accordingly

If the gestational sac is above it: it is mostly a normal implantation

Sensitivity = 93.0%,

Specificity = 98.9%,

PPV = 96.4%,

NPV = 97.9%.

On a panoramic, longitudinal, sagittal scan determine the locationof the gestational sac. Divide the uterus in half by an imaginary line

Am J Obstet Gynecol 2016;215:225

UOG 2017

CSO2+

CSO2-

CSO1

If you combine the two methods to diagnose CSP…….

• Antero-Inferior Uterine ‘CSP risk’ Triangle

‘Timor line’ ‘Cali line’

Not published!

Step #2 : measure bladder-to-sac distance

Measure bladder-to-sac distance

• Rarely is there information about bladder-to-sac distance or overlying myometrial thickness

• The literature is not only confusing as to the sac location, but…..

• Furthermore , usually there is no distinction between “gestational sac” and “placenta”

• Lastly, there is rarely any mention about location of placental vascularization

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To correctly measure the sac-to-bladder distance, we need a precise

definition of implantation, since it may determine outcome

Sporadically, but increasingly, we hear and read that there may be a

distinction between implantation “on the scar tissue” and “in the niche

(dehiscence)”

On the scar or in the “niche”….??• The literature is confusing as to location of the sac:

– ON the scar with a chance to proceed to 3rd ∆ (so called “low lying sacs”)

– IN the niche, SURROUNDED by myometrium, seldomproceeds to term (so called “true” CSPs)

• Confusing??……….TRUE: Differentiation at time is very hard

• Recent reviews of ‘scar pregnancies’ include both types because both were managed by injection & D&C.

--Surapanini K, Silberzweig JE. Cesarean section scar diverticulum: appearance on hysterosalpingography. Am J Roentgenol 2008;190:870–4.--Jurkovic D, Hillaby K, Woelfer B, Lawrence A, Salim R, Elson CJ. First-trimester diagnosis and management of pregnancies implanted into the lower uterine segment Cesarean section scar. UOG 2003;21:220–7.-- Comstock CH, Bronsteen RA. The antenatal diagnosis of placenta accreta. BJOG 2014;121:171–182--Timor-Trisch IE, Monteagudo A, Santos R, Tsymbal T, Pineda G, Arslan AA. The diagnosis, treatment and

follow-up of cesarean scar pregnancy. AJOG 2012;207:44. e1–13.

Hard to detect any organization • Comstock: “Low lying: versus--surrounded

by myometrium”

-- Comstock CH, Bronsteen RA. The antenatal diagnosis of placenta accreta. BJOG 2014;121:171–182-- Twickler DM, Lucas MJ, Balis AB, et al. Color flow mapping for myometrial invasion in women with a prior cesarean delivery. J Matern Fetal Med2000; 9:330–335.Does the presence of a Caesarean section scar affect implantation site and early pregnancy outcome in women attending an early pregnancy assessment unit?--Naji O, Wynants L, Smith A, Abdallah Y, Saso S, Stalder C, Van Huffel S, Ghaem-Maghami S, Van Calster B, Timmerman D, Bourne T.Hum Reprod. 2013 Jun;28(6):1489-96.Sonographic Findings of Morbidly Adherent Placenta in the First Trimester--Rac MW, Moschos E, Wells CE, McIntire DD, Dashe JS, Twickler DM.J Ultrasound Med. 2016 Feb;35(2):263-9

• Twickler: < 1mm predicted MAP

• Naji: away from scar, close to scar, crossing the scar, inside the scar (CSP)

• Rac: smallest anterior myometrial thickness

on 1st ∆ sonography significantly improved detection of morbidly adherent placenta.

Here is my understanding of the issue of implantation after years of observations

of adherence disorders and cesarean scar pregnancies:

It is clear that there is no uniform and agreed upon definition of the type

and depth of implantation placental and its correlation to outcome

My definition of EARLY sonographic appearance: Placenta implanted …”on the scar”…

7w4d

} Scar CxCavity

Gest sac

The relevant thickness has yet to be determined

8w2d

My definition of EARLY sonographic appearance: Placenta implanted ..…”in the niche”…

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ALWAYSstay focused upon the proximity of theplacenta to the anterior uterine surface

or the bladder

Have you ever looked at the location of the SAC in CSPs mainly after 7-8 weeks being half-way

in the uterine cavity?

7w4d 8w2d

Rely on the patient’s Hx, location of the placentaand its vascular supply!!

At times (mostly after 7 weeks) the location of the sac may be misleading.

It is still a scar pregnancy!!

Pregnancy with placenta implanted in the niche of the previous C/S

Bladder

6 weeks7 weeks9 weeks

Cervix

Pregnancy growing with sac moving towards the uterine cavity

Pregnancy growing fully into uterine cavity. Placenta with vessels stays anchored within the niche

We tried to learn if there is a difference in pregnancy outcome as a function of the distance between the

gestational sac and the anterior uterine surface/bladder

Prognostic signs based upon the depth of implantation

It is suspected that CSPs implanted within a dehiscent scar (“niche”) behave differently compared to CSPs implanted on top of a thick fibrous scar.

No such studies are available

We assessed the natural development and pregnancy outcomes of CSP implanted either “on the scar” or “in the niche”.

Am J Obstet Gynecol 2017;215:510

• Retrospective, multi-center study of 17 CSP patients between 5-9 wks

• Group A: “on the scar” = 6 patients

• Group B: “in the niche” = 11 patients

• Measured: Myometrial thickness overlying the placenta

• Compared: gestational age and mode of delivery, blood loss at delivery, neonate weight and

placental histopathology.

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Cesarean scar pregnancy implanted “on the scar”

KAELIN AGTEN A., CALI G., MONTEAGUDO A., OVIEDO J. TIMOR-TRITSCH I.E. he clinical outcome of cesarean scar pregnancies implanted “on the scar” versus “in the niche. AJOG 2016

Cesarean scar pregnancies implanted “in the niche”.

KAELIN AGTEN A., CALI G., MONTEAGUDO A., OVIEDO J. TIMOR-TITSCH I.E. he clinical outcome of cesarean scar pregnancies implanted “on the scar” versus “in the niche. AJOG 2016

Example of a patient with CSP implanted “on the scar” with a normal placenta at delivery.

10 weeks 14 weeks

22 weeks 28 weeks 32 weeks

Example of a patient with CSP implanted “in the niche” with placenta percreta at delivery.

9 weeks 22 weeks

28 weeks

Parameter

Group A‘On scar’

Group B‘In niche’

P value

n 6 11

GA @ delivery (wks) 38 34 0.001

Mode of delivery 6 CD 1 with

MAP

10 CD all with

MAP

Cesarean hysterectomy

1 C-Hyst for

Morbidly Adhrent Plac

10 C-Hyst MAP

1 gravid hyst @ 20 weeks for bleeding

Est blood loss (ML) 700 1200 NS

Myometrial thickness @ the scar

5mm (range 4-9) 1mm (0-2) 0.001

MAP=Morbidly adherent placenta

Results

17 CSPs

KAELIN AGTEN A., CALI G., MONTEAGUDO A., OVIEDO J. TIMOR-TrITSCH I.E. he clinical outcome of cesarean scar pregnancies implanted “on the scar” versus “in the niche. AJOG 2016

What did we learn?

• Patients with CSP implanted “on the scar” had a substantial better outcome compared to patients with CSP “in the niche”.

• Myometrial thickness below 2mm in the 1st trimester US was associated with Morbidly Adherent Placenta at delivery.

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We tried to learn if there is a difference in pregnancy outcome as a

function of presence or absence detecting known and “classical”

sonographic characteristics of AIP

Prognostic ultrasound features based upon the “classical” US signs

of AIP

Are there classical US signs of AIP present already in the 1st trimester?

• First-- What are the “classical” signs of MAP/AIP in the 2nd and 3rd trimesters?:

– Low* anterior** implantation

– Lacunae

–No clear anechoic space

– Increased vascularity

–Altered bladder line

*Timor-Tritsch IE, Monteagudo A, Cali G, El Refaey H, Kaelin Agten A, Arslan AA.Easy sonographic differential diagnosis between intrauterine pregnancy and cesarean delivery scar pregnancy in the early first trimesterAm J Obstet Gynecol. 2016;215:225**Cali G, Forlani F, Timor-Tritsch IE, Palacios-Jaraquemada J, Minneci G, D'Antonio F.Natural history of Cesarean scar pregnancy on prenatal ultrasound: the crossover sign.Ultrasound Obstet Gynecol. 2017;50:100-104.

Are there classical US signs of AIP present already in the 1st trimester?

• Look at the “classical” signs of MAP/AIP!:

*Timor-Tritsch IE, Monteagudo A, Cali G, El Refaey H, Kaelin Agten A, Arslan AA.Am J Obstet Gynecol. 2016;215:225**Cali G, Forlani F, Timor-TritschIE, Palacios-Jaraquemada J, Minneci G, D'Antonio F. UO G. 2017;50:100-104.

Low* anterior** implantation

Lacunae

Altered bladder line

No clear anechoic space

Increased vascularity

10 weeks 1 day

Disappearance of the clear myometrial line

Large number of Lacunae

Unusually increased vascularity at the

placental insertion

Are there classical US signs of AIP present already in the 1st trimester?

Answer: Yes they are:

First trimester diagnosis of abnormally invasive placenta:a systematic review and meta-analysis• Objectives: to ascertain whether US signs suggestive of MAP

are present in the 1st Δ and they predict MAP

• Results: Nine studies (578 pregnancies at risk for MAP)

• At least one US sign suggestive of MAP was detected in 83.7% (95% CI 61.3-97.5) of cases with confirmed MAP

• Conclusions: US signs of MAP are already present during the 1st Δ, especially before 11 weeks of gestation and are those typical of a caesarean scar pregnancy (CPS).

• Low implantation of the sac was the most common US sign associated with MAP in the 1st Δ of pregnancy

D’Antonio1, Timor-Tritsch, Palacios-Jaraquemada, Monteagudo, Buca, Forlani, Minneci, Foti, Manzoli, Acharya, Calì. Ultrasound in Obstetrics and Gynecology 2017 In Press

Are the classical US signs of AIP present already in the 1st trimester?

• In the first trimester :

Cali G, Forlani F, Timor-Tritsch IE, Palacios-Jaraquemada J, Minneci G, D'Antonio F.: Accepted UOG 2017.

Seen in 75-85%at 11-14w:

No clear anechoic space

Increased vascularity

Altered bladder line

Lacunae

Low, anterior implantation: seen in 100% at ≤10w

Cx

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Gray scale and color Doppler. Evolution of the placenta from CSP to MAP

10w 1d

16w 5d

23w 5d 24w 5d 36w 3d

Lacunae Vascularity

Conclusion

Over the last several years an increasing number of authors gathered significant experience that allows to provide evidence based counseling to patients presenting with a CSP

We are not yet at a point where we can translate the gained experience into reliable risk assessment

More research & clinical observations are needed in the form of an international CSP registry

We need to introduce routine US scanning at 6-8 weeks for all patients with a history of previous CS

Suggested management of CSPCSP

No FHFH +

Recheck q 3 days

No FH after 3 scans or at 7

wks by reliable dating

Follow by US and by hCGuntil zero!

Select aproprate Rx Stop heart without

delay: Inject; Double balloon:Hysterotomy or

Gravid hysterectomy?

Monitor hCG& US weekly. Watch for

possible EMV

Determine if placenta/ gestational sac is on the scar or in

the niche. MEASURE MYOMETRIAL THICKESS

Patientrequests

TOP

Patient interested in continuing pregnancy

Available evidence based counseling

“on the scar” or ≥ 5mm: low risk for MAP (accreta) and

cesarean hysterectomy

“in the niche” or ≤ 5mm: high risk for

MAP (increta, percreta) and

cesarean hysterectomy

Last Suggestion:

Early recognition of CSP starts with Patient and Physician education:

When discharging patients from the hospital after a C/D make sure to tell

her to present to the Ob/Gyn the day after the first positive pregnancy

test for an US scan between 6-7 weeks.

If I have time I would like to show you our new, minimally invasive

treatment method of CSP

The use of a double, cervical ripening balloon catheter as a single, minimally

invasive treatment of CSP and CxP

Timor-Tritsch & Monteagudo Am J Obstet Gynecol March 2016

Ilan E. Timor-Tritsch, Ana Monteagudo, Terri-Ann Bennett, Christine Foley, Joanne Ramos, Andrea Kaelin

AgtenAmerican Journal of Obstetrics and Gynecology, Volume 215, Issue 3, 2016, pp. 351.e1-351.e8

Am J Obstet Gynecol. 2016 Sep;215(3):351.

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Reasons for its use:

– Simultaneously terminates pregnancy and prevents bleeding

– Simplify treatment; Minimize patient discomfort

– Adapt a catheter familiar to Ob in the L&D to treat CSP

– Also effective for cervical pregnancies

The double balloon

catheter

The balloons inflated

Lately: New, minimally invasive treatment: Placing a double cervical ripening balloon

Timor-Tritsch, Monteagudo, Bennett, Foley, Kaelin Agten. A new minimally invasive

treatment for cesarean scar and cervical pregnancy. Article accepted for publication by AJOGTimor-Tritsch & Monteagudo Timor-Tritsch & MonteagudoTimor-Tritsch et al AJOG 2016

Anchor balloon

Pressure

balloon

Gestational sac of

CSP

Timor-Tritsch & Monteagudo Timor-Tritsch et al AJOG 2016

• 32 CSPs & 3 CxPs 35 patients were treated (6-8wks)

• Catheter placement & balloon inflation tolerated well.

• Oral pain medication and antibiotics. IM MTX were given

• Last 12 patients received paracervical block (1% Lidocaine)

• Balloons deflated, catheter removed 1-3 days

• Minimal, “old”, dark blood was seen after removal of the catheters from intra-cavitary accumulation of blood

• In all cases almost total resolution of the hCG, the sac site & its vascularity was seen within 20 -60 days

The NEW experience: 5 centers*

Timor-Tritsch & Monteagudo

• Nyu/Bellevue Medical centers: 21cases• Carnegie Imaging (Drs Rebarber and Monteagudo): 4 cases• Lenox Hill, MFH (Dr Bornstein) 3 case• Einstein Medical college 2 cases• Michigan Stae university 3 cases• Texas Medical center 1 case

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Extra slides

Reasons for its use:

– Simultaneously terminates pregnancy and prevents bleeding

– Simplify treatment; Minimize patient discomfort

– Adapt a catheter familiar to Ob in the L&D to treat CSP

– Also effective for cervical pregnancies

The double balloon

catheter

The balloons inflated

Lately: New, minimally invasive treatment: Placing a double cervical ripening balloon

Timor-Tritsch, Monteagudo, Bennett, Foley, Kaelin Agten. A new minimally invasive

treatment for cesarean scar and cervical pregnancy. Article accepted for publication by AJOGTimor-Tritsch & Monteagudo Timor-Tritsch & MonteagudoTimor-Tritsch et al AJOG 2016

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Results

• Pts discharged home within 2 hours

• Balloons remained in place mean 2 days

• hCG dropped in a mean 49 days

• No significant bleeding

• No further Rx needed

Timor-Tritsch, Monteagudo, Bennett, Foley,,Kaelin Agten. A new minimally invasive treatment for cesarean scar and cervical pregnancy. Article accepted for publication by the AJOG

Timor-Tritsch & Monteagudo

Timor-Tritsch et al AJOG 2016

Anchor balloon

Pressure

balloon

Gestational sac of

CSP

Timor-Tritsch & Monteagudo Timor-Tritsch et al AJOG 2016

• 32 CSPs & 3 CxPs 35 patients were treated (6-8wks)

• Catheter placement & balloon inflation tolerated well.

• Oral pain medication and antibiotics were given

• Last 12 patients received paracervical block (1% Lidocaine)

• Balloons deflated, catheter removed 1-3 days

• Minimal, “old”, dark blood was seen after removal of the catheters from intra-cavitary accumulation of blood

• In all cases almost total resolution of the hCG, the sac site & its vascularity was seen within 20 -60 days

• In the last 21 cases we used adjuvant systemic MTX

The New York experience: 6 centers*

Timor-Tritsch & Monteagudo

• *Nyu/Bellevue Medical centers: 25 cases• *Carnegie Imaging (Drs Rebarber and Monteagudo): 5 cases• *Lenox Hill, MFH (Dr Bornstein) 1 case• * Dr . M. (Michigan) 2 cases• * Einstein Dr, P. Dar 2 cases