Cesarean Scar Pregnancy

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Treatment Algorithm: Its Evolution & Our Experience

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Our Team

Stephen Contag scontag@umn.edu

Carrie Ann Terrell terre010@umn.edu

Sabrina Burn burn@umn.edu

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Disclosures

• No financial disclosures

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Outline

• Background, Management Options, & Early Algorithm
• Diagnostic Criteria
• UMMC Case Outcomes & Experience
• Management Review & Current Best Practice

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Background, Incidence, Early Algorithm

Carrie Ann Terrell

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CSP Incidence

• All Pregnancies: 1:1800 to 1:2656 pregnancies
• Among women with history of cesarean: 1 in 531
• Approximately half CSPs occur after 1 prior cesarean
• Delay in diagnosis or treatment results in significant maternal morbidity

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1. Fylstra DL. Ectopic pregnancy within a cesarean scar: a review. Obstet Gynecol Surv. 2002 Aug;57(8):537-43
2. Jurkovic D, Hillaby K, Woelfer B, Lawrence A, Salim R, Elson CJ. Cesarean scar pregnancy. Ultrasound Obstet Gynecol. 2003 Mar;21(3):310.
3. Seow KM, Huang LW, Lin YH, Lin MY, Tsai YL, Hwang JL. Cesarean scar pregnancy: issues in management. Ultrasound Obstet Gynecol. 2004 Mar;23(3):247-53.
4. McKenna DA, Poder L, Goldman M, Goldstein RB. Role of sonography in the recognition, assessment, and treatment of cesarean scar ectopic pregnancies. J Ultrasound Med. 2008 May;27(5):779-83

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CSP Proposed Mechanism

• Occurs when a blastocyst implants within a microscopic dehiscence tract in the scar from a prior cesarean delivery
• Implantation site is made of fibrous scar tissue with inherent deficiencies
• Increases risk for:
• Uterine dehiscence
• PAS (Placenta Accreta Spectrum aka Malplacentation)
• Exists along a common disease continuum
• Hemorrhage

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1. Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org, Miller R, Timor-Tritsch IE, Gyamfi-Bannerman C. Society for Maternal-Fetal Medicine (SMFM) Consult Series #49: Cesarean scar pregnancy. Am J Obstet Gynecol. 2020 May;222(5):B2-B14. doi: 10.1016/j.ajog.2020.01.030. Epub 2020 Jan 21. Erratum in: Am J Obstet Gynecol. 2020 Oct 6;: PMID: 31972162.

CSP Risk Factors

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CSP Presentation

• 35% Asymptomatic and incidentally identified by ultrasound
• 35% Painless vaginal bleeding prompting ultrasound
• 25% Pain prompting ultrasound

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*But can be more severe, especially if early diagnosis missed (ex: uterine rupture/hemoperitoneum)

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1. Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org, Miller R, Timor-Tritsch IE, Gyamfi-Bannerman C. Society for Maternal-Fetal Medicine (SMFM) Consult Series #49: Cesarean scar pregnancy. Am J Obstet Gynecol. 2020 May;222(5):B2-B14. doi: 10.1016/j.ajog.2020.01.030. Epub 2020 Jan 21. Erratum in: Am J Obstet Gynecol. 2020 Oct 6;: PMID: 31972162.

CSP Differential Diagnoses

• Literature review by Timor-Tritsch and Monteagudo in 2012 identified 751 CSP cases

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• 107 cases (13.6%) were originally misdiagnosed as
• Cervical ectopic pregnancies
• Spontaneous abortions in transit
• Low implantation of an intrauterine pregnancy

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CSP Treatment Modalities:

Natural history of expectant management

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Calì G, Timor-Tritsch IE, Palacios-Jaraquemada J, Monteaugudo A, Buca D, Forlani F, Familiari A, Scambia G, Acharya G, D'Antonio F. Outcome of Cesarean scar pregnancy managed expectantly: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018 Feb;51(2):169-175.

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CSP Treatment Modalities:

Suction curettage

• Was initially reported to be very rare…
• Most reports using suction curettage were unsuccessful or complicated
• The first published case report describing the successful management of a CSP with suction curettage was published in 2005
• 5 weeks gestation at time of procedure
• Performed with US guidance
• Complicated by vaginal bleeding requiring bimanual compression

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Arslan M, Pata O, Dilek TU, Aktas A, Aban M, Dilek S. Treatment of viable cesarean scar ectopic pregnancy with suction curettage. Int J Gynaecol Obstet. 2005 May;89(2):163-6. doi: 10.1016/j.ijgo.2004.12.038. PMID: 15847889.

CSP Treatment Modalities:

Suction curettage

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Jurkovic D, Knez J, Appiah A, Farahani L, Mavrelos D, Ross JA. Surgical treatment of Cesarean scar ectopic pregnancy: efficacy and safety of ultrasound-guided suction curettage. Ultrasound Obstet Gynecol. 2016 Apr;47(4):511-7.

CSP Treatment Modalities: �Single dose Systemic Methotrexate

• Dosing
• MTX 50 mg IM with repeat dose PRN and citrovorum rescue

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• Requirements
• Stable
• Asymptomatic/No pain
• <8 wk GA
• Myometrial thickness <2 mm
• β hCG <5000
• GS 2.5 cm and/or no embryo and/or or no CA

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CSP Treatment Modalities:�Multi-dose methotrexate

• Cycle 1:
• Day 1: methotrexate 1 mg/kg IM
• Day 2: leucovorin 0.1 mg/kg PO (the smallest size for leucovorin tablets is 5 mg tablets; thus, round up to the nearest 5 mg dose)
• Send patient home after methotrexate injection on day 1 with prescription (available at Fairview Riverside Outpatient Pharmacy) for leucovorin dose for day 2, 4, 6, 8 and 10 and MTX appointment for day 3
• Cycle 2:
• Before treatment: check quantitative β-hCG, AST/ALT and creatinine. Withhold repeat MTX dose if β-hCG has decreased (~50%) or significant elevation in AST or creatinine.
• Day 3: methotrexate 1 mg/kg IM
• Day 4: leucovorin 0.1 mg/kg PO
• Send patient home after methotrexate injection day 3 with MTX appointment for day 5
• Cycle 3: follow same directions for cycle 2
• Cycle 4: follow same directions for cycle 2
• Cycle 5: follow same directions for cycle 2

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CSP Treatment Modalities:

Hysteroscopy

• Concurrent systemic MTX and Hysteroscopic resection

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CSP Treatment Modalities:

Hysteroscopy

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PRE-PROCEDURE

POST-PROCEDURE

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Wang G, Liu X, Bi F, Yin L, Sa R, Wang D, Yang Q. Evaluation of the efficacy of laparoscopic resection for the management of exogenous cesarean scar pregnancy.

Fertil Steril. 2014 May;101(5):1501-7.

CSP Treatment Modalities: �Laparoscopy

* Of note, subjectively this has been felt to be the best approach by our WHS Providers.

• Allows for removal of thin attenuated tissue
• Re-approximates healthy tissue

• Forty cases in one series
• Through the anterior fornix
• Transverse incision uterus
• Suction curettage
• Closure

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Huanxiao Z, Shuqin C, Hongye J, Hongzhe X, Gang N, Chengkang X, Xiaoming G, Shuzhong Y. Transvaginal hysterotomy for cesarean scar pregnancy in 40 consecutive cases. Gynecol Surg. 2015;12(1):45-51.

CSP Treatment Modalities: �CSP resection, transvaginal approach

CSP Treatment Modalities:

Hysterectomy

• Definitive management of CSP with hysterectomy or removal of uterus with in situ CSP is an alternative surgical option

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• Particularly appropriate for:
• Early second-trimester CSP presentations
• Women who do not desire future fertility.

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Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org, Miller R, Timor-Tritsch IE, Gyamfi-Bannerman C. Society for Maternal-Fetal Medicine (SMFM) Consult Series #49: Cesarean scar pregnancy. Am J Obstet Gynecol. 2020 May;222(5):B2-B14.

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CSP Treatment Modalities:

Uterine Artery Embolization (UAE)

• UAE with surgery is more effective that UAE with MTX alone
• Limited evidence using UAE and curettage with adequate results
• Most studies using UAE report sequence of methotrexate, UAE, and curettage.

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• More effective in reducing intra-procedural blood loss:
• in larger pregnancies
• those with evidence of large AVM

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CSP Treatment Modalities:

Uterine Artery Embolization (UAE)

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Tang Y, Zhang Y, Tang H, Che J, Feng H, Yao X, Chen Q. A Comparison of Ultrasound Guided Curettage With and Without Uterine Artery Embolization on Controlling Intraoperative Blood Loss for a Cesarean Scar Pregnancy Treatment: Study Protocol for a Randomized Clinical Trial. Front Endocrinol (Lausanne). 2021 Jun 7;12:651273

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**Criteria Not Met for UAE

**Criteria Met for UAE

Referral to MFM

Scan & Diagnose Endogenic (Type I) vs. Exogenic (Type II)

Referral to WHS

Review woman’s intent regarding pregnancy, future childbearing

1. Counsel on Medical management
2. Counsel on Surgical management
3. Counsel on Combination management
4. Counsel on Expectant management (if endogenic and no FCA)

Medical Management with MTX Multiple ("High") Dose Regimen*

1. Labs: Rh, β hCG, Hgb, AST/ALT, Cr
2. MTX 1 mg/kg IM Day 1, 3, 5, 7, 9
3. Folinic acid (Leucovorin) 0.1 mg/kg PO Day 2, 4, 6, 8, 10

MFM Ultrasound 7-14 days after medical management for:

1. Sac diameter
2. Myometrial thickness
3. Vascularity

EPIC

1. Snapshot
2. Registry (as QI)

INTERDIVISIONAL C/S SCAR PREGNANCY PROTOCOL

Last updated 7/29/2020 – Christy Boraas, MD, MPH

Medical Therapy

IR Consult for UAE

**Criteria for UAE

1.Ongoing FCA

2.β hCG does not decrease by 50%

3.Gestational Sac size increases

4.MSD > 5 cm

5.Myometrial thickness < 2 mm

6.Significant vascularity at LUS

a)

d)

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Resolution

Surgical Management

Woman desires definitive management, childbearing complete

Surgical Management

*See SOP on Multidose Regimen.

Consider Expectant Management with serial β-hCG

Patient declines

CSP Treatment Modalities: �Needle aspiration and local MTX

• Transvaginal approach
• Aspiration of sac prior to methotrexate
• General anesthesia if using large needle (16-18 g)

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• Requirements:
• Stable
• Asymptomatic/No pain
• B-hCG > 10,000 IU/L
• GS >2.5 cm and/or presence of cardiac activity

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CSP Treatment Modalities: �Systemic and Local Methotrexate

• Dosing
• Systemic: MTX 50 mg IM with repeat dose PRN and citrovorum rescue
• Local: Intra-gestational sac injection with MTX 50 mg (20-22 g needle)

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• Requirements
• Stable
• Asymptomatic/No pain
• B-hCG > 10,000 IU/
• GS >2.5 cm and/or presence of cardiac activity

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• Advantages
• Higher MTX concentration at the CSP
• More rapid termination of the pregnancy

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Timor-Tritsch IE, Khatib N, Monteagudo A, Ramos J, Berg R, Kovács S. Cesarean scar pregnancies: experience of 60 cases. J Ultrasound Med. 2015 Apr;34(4):601-10

Timor-Tritsch & Monteagudo:

2012 Review of Literature

• 751 cases of CSP

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• Highest complication rates (n;%):
• Intramuscular methotrexate alone (54/87 cases; 62.1%)
• Curettage alone or in combination with other modalities (189/305 cases; 61.9%)
• UAE alone or in combination with other modalities (30/64 cases; 46.9%).

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• Lowest complication rates:
• Local intragestational injection of methotrexate or KCl (8/81 cases; 9.6%)
• Hysteroscopy alone or in combination (22/119 cases; 18.4%)

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Timor-Tritsch IE, Monteagudo A. Unforeseen consequences of the increasing rate of cesarean deliveries: early placenta accreta and cesarean scar pregnancy. A review. Am J Obstet Gynecol. 2012 Jul;207(1):14-29.

Birch Petersen, Hoffmann et al:

2016 Systematic Review

• 2037 cases of CSP

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• Highest complication rates:
• Expectant management (41.5% success, 53.7% complications)
• Curettage (n=243; 48.1% success, 21% complications)
• UAE and methotrexate (n=427; 68.6% success, 2.8% complications)
• Systemic methotrexate (n=339; 75.2% success, 13% complications),
• Combined local and systemic methotrexate (n=34; 76.5% success, 2.3% complications).

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• Lowest complication rates:
• Transvaginal CSP resection (n=118; 99.2% success, 0.9% complications),
• Laparoscopy (n=69; 97.1% success, 0% complications)
• UAE with curettage, hysteroscopy, or both (n=85; 95.4% success, 1.2% complications)
• UAE alone (n=295; 93.6% success, 3.4% complications).

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Birch Petersen K, Hoffmann E, Rifbjerg Larsen C, Svarre Nielsen H. Cesarean scar pregnancy: a systematic review of treatment studies. Fertil Steril. 2016 Apr;105(4):958-67.

Summary of Data

1. Combined therapy is better than medical or surgical alone
2. Surgical therapy with excision is safe but costlier and not universally available
3. Local MTX is better than systemic MTX alone
4. Combined MTX is better than either alone
5. UAE is as effective as MTX in preventing procedural blood loss
6. UAE after MTX is better than UAE without MTX, especially with more vascular or larger pregnancies
7. Suction curettage is safer than sharp curettage
8. Medical therapy prior to surgical therapy can be effective in 4/5 cases and easier to access
9. Procedural blood loss can be controlled with balloon tamponade

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Diagnostic Criteria

Stephen Contag

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Diagnostic Criteria:

Pre 2020

• First formal US criteria (Vial, Petignat et al. 2000)
• Trophoblast between bladder and anterior uterine wall
• No visible fetal parts in the uterus
• Discontinuity of the anterior uterine wall on sagittal view
• Contemporary criteria (Timor-Tritsch, Monteagudo et al. 2012)

(1) an empty uterine cavity and endocervix

(2) placenta, gestational sac, or both embedded in the hysterotomy scar

(3) a triangular (< 8w) or rounded or oval (>8w) gestational sac that fills the scar “niche” (the shallow area representing a healed hysterotomy site)

(4) a thin (1 to 3 mm) or absent myometrial layer between the gestational sac and bladder

(5) a prominent or rich vascular pattern in the cesarean scar

(6) an embryonic or fetal pole, yolk sac, or both with or without fetal cardiac activity

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Diagnostic Criteria:

2020

• Ultrasound is the primary method
• Greyscale
• Color Doppler
• Full bladder
• Sensitivity 85% (Rotas, Haberman et al. 2006)
• Earlier diagnosis with improvements in US
• Average age at diagnosis is 7.5 +/- 2.5 weeks
• TVUS has highest resolution
• Clinical suspicion has improved detection rates
• No benefit using 3D US
• No added benefit with MRI unless US inconclusive

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Birch Petersen K, Hoffmann E, Rifbjerg Larsen C, Svarre Nielsen H. Cesarean scar pregnancy: a systematic review of treatment studies. Fertil Steril. 2016 Apr;105(4):958-67.

Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org, Miller R, Timor-Tritsch IE, Gyamfi-Bannerman C. Society for Maternal-Fetal Medicine (SMFM) Consult Series #49: Cesarean scar pregnancy. Am J Obstet Gynecol. 2020 May;222(5):B2-B14.

CSP Categorization

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Endogenic or “on the scar”

Exogenic or “in-the-niche”

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IMAGES

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Al Naimi A, Mouzakiti N, Hondrich M, Louwen F, Bahlmann F. The B-mode sonographic evaluation of the post-caesarean uterine wall and its methodology: A study protocol. J Obstet Gynaecol Res. 2020 Oct 22.

Hysterosonogram:

Non-pregnant uterus

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Hysterosonogram:

Pregnant uterus

Al Naimi A, Mouzakiti N, Hondrich M, Louwen F, Bahlmann F. The B-mode sonographic evaluation of the post-caesarean uterine wall and its methodology: A study protocol. J Obstet Gynaecol Res. 2020 Oct 22.

Pre and post conception assessment of lower uterine isthmus/segment

• Median scar thickness prior to and at 11-14 weeks was 6.1 mm (3.7 to 8.6 mm)

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Baranov A, Salvesen KÅ, Vikhareva O. Assessment of Cesarean hysterotomy scar before pregnancy and at 11-14 weeks of gestation: a prospective cohort study. Ultrasound Obstet Gynecol. 2017 Jul;50(1):105-109.

Pre and post conception assessment of lower uterine isthmus/segment

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Baranov A, Salvesen KÅ, Vikhareva O. Assessment of Cesarean hysterotomy scar before pregnancy and at 11-14 weeks of gestation: a prospective cohort study. Ultrasound Obstet Gynecol. 2017 Jul;50(1):105-109.

Diagnostic modalities:

Crossover sign

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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 Jul;50(1):100-104.

Diagnostic modalities:

Crossover sign

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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 Jul;50(1):100-104.

Diagnostic modalities:

Crossover sign

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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 Jul;50(1):100-104.

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UMMC CSP Images

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UMMC CSP Images

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UMMC Case Outcomes & Experience

Sabrina Burn

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UMMC Cases (n=23)

2016-2020

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UMMC Cases

2016-2020

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UMMC Cases

2016-2020

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UMMC Cases

2016-2020

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Management Review & Current Best Practice

Sabrina Burn

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Society for Maternal-Fetal Medicine (SMFM)�Consult Series #49: Cesarean scar pregnancy

• We recommend against expectant management of CSP (GRADE 1B).

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• Exception
• Early CSP characterized by fetal death
• Evidence of pregnancy failure
• CSP may take several months for a nonviable CSP to resolve
• Can be associated with development of arteriovenous malformation (AVM)

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1. Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org, Miller R, Timor-Tritsch IE, Gyamfi-Bannerman C. Society for Maternal-Fetal Medicine (SMFM) Consult Series #49: Cesarean scar pregnancy. Am J Obstet Gynecol. 2020 May;222(5):B2-B14. doi: 10.1016/j.ajog.2020.01.030. Epub 2020 Jan 21. Erratum in: Am J Obstet Gynecol. 2020 Oct 6;: PMID: 31972162.
2. Timor-Tritsch IE, Haynes MC, Monteagudo A, Khatib N, Kovács S. Ultrasound diagnosis and management of acquired uterine enhanced myometrial vascularity/arteriovenous malformations. Am J Obstet Gynecol. 2016 Jun;214(6):731.e1-731.e10.

Expectant management counseling

• Women who decline treatment
• Should be counseled on risk of
• PAS
• Massive hemorrhage
• Uterine rupture
• Severe maternal morbidity & even mortality

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• Delivery
• Repeat cesarean delivery between 34 0/7 and 35 6/7 weeks (GRADE 1C)
• Antenatal corticosteroids
• Preparation for massive transfusion protocol

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Society for Maternal-Fetal Medicine (SMFM)�Consult Series #49: Cesarean scar pregnancy

• We suggest operative resection (with transvaginal or laparoscopic approaches when possible) or ultrasound guided vacuum aspiration be considered for surgical management of CSP and that sharp curettage alone be avoided (GRADE 2C)

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• Remember uterine curettage alone has low success
• Difficulty in removing all tissue
• Risk for perforation
• Scar has poor contractility
• Risk of hemorrhage
• High intervention rates (52%)

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Society for Maternal-Fetal Medicine (SMFM)�Consult Series #49: Cesarean scar pregnancy

• We suggest intragestational methotrexate for medical treatment of CSP, with or without other treatment modalities (GRADE 2C). We recommend that systemic methotrexate alone not be used to treat CSP (GRADE 1C).

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• Efficacy:
• Single local methotrexate success rate: 73.9%
• After additional local or intramuscular success rate: 88.5%

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• Failed methotrexate treatment required surgery: 11.5%
• Other reviews report failure rates 5 to ≥15% after using local MTX alone or in combination with systemic
• Serum human chorionic gonadotropin levels higher than 100,000 IU/L

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Future Fertility Counseling

• We recommend that women with a CSP be advised of the risks of another pregnancy and counseled regarding effective contraceptive methods, including long-acting reversible contraception and permanent contraception (GRADE 1C).

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• Considerations:
• Increased risk for recurrence of CSP: 5-40%
• Recommend waiting 12 to 24 months before pregnancy
• Ultrasound surveillance required

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http://csp-registry.com

Questions?

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