Ectopic PregnancyEctopic Pregnancy

Dr. Yasir KatibDr. Yasir KatibMBBS, FRCSC, MBBS, FRCSC, PerinatologistPerinatologist

Introduction Introduction

Ectopic pregnancy occurs when Ectopic pregnancy occurs when the developing blastocyst becomes the developing blastocyst becomes implanted at a site other than the implanted at a site other than the endometrium of the uterine cavityendometrium of the uterine cavity

The most common extra-uterine The most common extra-uterine location is the fallopian tube, which location is the fallopian tube, which accounts for 98%accounts for 98%

Types of EPTypes of EP

Sites of EPSites of EP

Fallopian tubeFallopian tube

AmpullaAmpulla 80%80%

IsthmusIsthmus 12%12%

Fimbrial endFimbrial end 5%5%

Cornual & interstitialCornual & interstitial 2%2%

AbdominalAbdominal 1.4%1.4%

OvarianOvarian 0.2%0.2%

CervicalCervical 0.2%0.2%

Heterotopic Pregnancies: 1 in 30 000

EpidemiologyEpidemiology 22ndnd leading cause of overall maternal mortality leading cause of overall maternal mortality

in USin US

Leading cause of pregnancy-related deaths Leading cause of pregnancy-related deaths during T-1during T-1

1-2% of all diagnosed pregnancies1-2% of all diagnosed pregnancies

EpidemiologyEpidemiology

Incidence is Incidence is incidence of salpingitis d/t chlamydia or incidence of salpingitis d/t chlamydia or

other STIother STI Improved diagnostic techniquesImproved diagnostic techniques ageage Blacks >non-whites>whitesBlacks >non-whites>whites

Most occur in multigravid women Most occur in multigravid women > 50% in women with > 50% in women with 3 pregnancies 3 pregnancies

10-15% in nulligravid women10-15% in nulligravid women

MortalityMortality

Causes 15% of maternal deathsCauses 15% of maternal deaths Overall risk of death 10X > the risk of Overall risk of death 10X > the risk of

childbirth; 50X > risk of legal abortionchildbirth; 50X > risk of legal abortion Cause of death dueCause of death due

blood loss (80%)Iblood loss (80%)I infection (3%)infection (3%) anesthesia (2%)anesthesia (2%)

Interstitial & abdominalInterstitial & abdominal 5X > risk of 5X > risk of death than other sitesdeath than other sites

Of Historical Note…….Of Historical Note…….

16931693 11stst documentation of unruptured ectopic documentation of unruptured ectopic

17521752 Infertility linked to EPInfertility linked to EP

mid 19mid 19thth century century Path reports stressed pelvic inflammation Path reports stressed pelvic inflammation

as cause of EPas cause of EP 1800s1800s

30 abd operations in (5 women survived)30 abd operations in (5 women survived) If not treated, 1 out of 3 survived (better!)If not treated, 1 out of 3 survived (better!)

Risk Factors for EPRisk Factors for EP

Definite (high risk)Definite (high risk) Previous EPPrevious EP Any tubal surgery or sterilization Any tubal surgery or sterilization

procedureprocedure In-utero DES exposure In-utero DES exposure 

Risk Factors for EPRisk Factors for EP

Probable (modrate risk)Probable (modrate risk) PIDPID InfertilityInfertility ““Superovulating agents” Superovulating agents”

Pergonal, Clomiphene citratePergonal, Clomiphene citrate Multiple sexual partners Multiple sexual partners  Smoking Smoking

Risk Factors for EPRisk Factors for EP

Uncertain Association (low risk)Uncertain Association (low risk) IUCDIUCD Vaginal douching Vaginal douching  Maternal age (extremes)Maternal age (extremes) Use of reproductive techniquesUse of reproductive techniques

In vitro fertilizationIn vitro fertilization Gamete intrafallopian transferGamete intrafallopian transfer Embryo transferEmbryo transfer

Classic TRIAD of EPClassic TRIAD of EP

1.1. Delayed mensesDelayed menses

2.2. Irregular vaginal bleedingIrregular vaginal bleeding

3.3. Abdominal painAbdominal pain

Most commonly Most commonly NOT NOT encountered encountered

Symptoms of Ectopic Symptoms of Ectopic PregnancyPregnancy

SYMPTOMSYMPTOM PTS WITH PTS WITH SYMPTOMSYMPTOM

Abdominal painAbdominal pain 90-100%90-100%

AmenorrheaAmenorrhea 75-95%75-95%

Vaginal bleedingVaginal bleeding 50-80%50-80%

Dizzininess, faintingDizzininess, fainting 20-35%20-35%

Pregnancy symptomsPregnancy symptoms 10-25%10-25%

Urge to defecateUrge to defecate 5-15%5-15%

Passage of tissuePassage of tissue 5-10%5-10%

Signs of EPSigns of EPSIGNSIGN PTS WITH SIGNPTS WITH SIGN

Adnexal tendernessAdnexal tenderness 75-90%75-90%

Abdominal tendernessAbdominal tenderness 80-95%80-95%

Adnexal mass*Adnexal mass* 50%50%

Uterine enlargementUterine enlargement 20-30%20-30%

Orthostatic changesOrthostatic changes 10-15%10-15%

FeverFever 5-10%5-10%

* 20% of masses occur on the side opposite the EP.

Differential DiagnosisDifferential Diagnosis Complication of IUPComplication of IUP

AbortionAbortion Early pregnancy plus uterine fibroid or Early pregnancy plus uterine fibroid or

ovarian tumourovarian tumour Conditions causing acute abd painConditions causing acute abd pain

Torsion of ovarian tumour, FT, or subserous Torsion of ovarian tumour, FT, or subserous pedunculated fibroidpedunculated fibroid

Salpino-oophoritisSalpino-oophoritis Pelvic pain with an IUCD Pelvic pain with an IUCD in situin situ Appendicitis Appendicitis

Differential Dx – cont’dDifferential Dx – cont’d

Conditions causing Conditions causing hemoperitoneumhemoperitoneum Ruptured corpus luteumRuptured corpus luteum Ruptured follicular cystRuptured follicular cyst Ruptured endometriotic cystRuptured endometriotic cyst

Conditions simulating a pelvic Conditions simulating a pelvic hematocelehematocele Retroverted gravid uterusRetroverted gravid uterus Pelvic or tubo-ovarian abcessPelvic or tubo-ovarian abcess

Management of EPManagement of EP

Pre-operative diagnostic accuracy Pre-operative diagnostic accuracy of EP based on clinical features of EP based on clinical features alone is notoriously poor: ~50%alone is notoriously poor: ~50%

20% of EP occur as surgical 20% of EP occur as surgical emergenciesemergencies

Delay is justified only to correct Delay is justified only to correct shockshock

Acute Management of EPAcute Management of EP

Remember your ABCsRemember your ABCs OxygenOxygen Large bore IV(s) Large bore IV(s) crystalloids crystalloids Blood Blood

LabsLabs CBC, coagulation studies, T & CCBC, coagulation studies, T & C -hCG-hCG

Usefulness of Quantitaive Usefulness of Quantitaive -hCG-hCG

Assessment of pregnancy viabilityAssessment of pregnancy viability Serial rise usually indicates a normal Serial rise usually indicates a normal

pregnancypregnancy Correlation with ultrasonographyCorrelation with ultrasonography

With titers > 1500 IU/L, TVUS should ID an IUPWith titers > 1500 IU/L, TVUS should ID an IUP With multiple gestation, a gestational sac will With multiple gestation, a gestational sac will

not be apparent until titer rises a little highernot be apparent until titer rises a little higher Assessment of treatment resultsAssessment of treatment results

Declining levels are c/w effective medical or Declining levels are c/w effective medical or surgical Tx; if levels persistsurgical Tx; if levels persist think GTD think GTD

The Importance of TVUSThe Importance of TVUS

Documentation of an intrauterine Documentation of an intrauterine sacsac A viable IUP should be identified when A viable IUP should be identified when

-hCG > 1500 IU/ml-hCG > 1500 IU/ml Adnexal massAdnexal mass

An EP > 2 cm should be identified An EP > 2 cm should be identified Adnexal cardiac activityAdnexal cardiac activity

Detectable when Detectable when -hCG is -hCG is ~ 15 000 – 20 000 ~ 15 000 – 20 000

U/S – Is it EP or U/S – Is it EP or miscarriage?miscarriage?

Surgical Management of Surgical Management of EPEP

RadicalRadical Salpingectomy with/out oophorectomySalpingectomy with/out oophorectomy

ConservativeConservative Salpingotomy Salpingotomy Salpingostomy or segmental resection Salpingostomy or segmental resection

does not does not repeat EP rate repeat EP rate fimbrial evacuation (traumatizes the fimbrial evacuation (traumatizes the

endosalphinx & is assoc with endosalphinx & is assoc with rate of rate of recurrent EP (24%) compared with recurrent EP (24%) compared with salpingectomysalpingectomy

Medical Management of Medical Management of EPEP

Methotrexate (MTX)Methotrexate (MTX) 11stst used in Japan in 1982 used in Japan in 1982 Antimetabolite that interferes with Antimetabolite that interferes with

dihydrofolate reductasedihydrofolate reductase Considered for low Considered for low -hCG-hCG Success rate 67%-94%Success rate 67%-94% IndicationsIndications

Hemodynamically stable pt Hemodynamically stable pt good F/Ugood F/U Recurrent EP following Sx Recurrent EP following Sx

interventionintervention

Methotrexate – cont’dMethotrexate – cont’d ContraindicationsContraindications

Evidence of ruptureEvidence of rupture Serum Serum -hCG > 5 000 IU/L (varies)-hCG > 5 000 IU/L (varies) FH detected on U/SFH detected on U/S Adnexal mass> 3.5 cm on U/SAdnexal mass> 3.5 cm on U/S Unreliable ptUnreliable pt F/U unavailableF/U unavailable Laparoscopy required to make dxLaparoscopy required to make dx Solid adnexal masses (germ cell Solid adnexal masses (germ cell

tumour)tumour) Free fluid > 30mlFree fluid > 30ml

Methotrexate ProtocolMethotrexate Protocol

Exclude contraindications as well asExclude contraindications as well as No evidence of renal, liver, or hematopoietic No evidence of renal, liver, or hematopoietic

disease (Bilirubin, AST,ALT, urea, Cr, CBC)disease (Bilirubin, AST,ALT, urea, Cr, CBC) Informed consentInformed consent

5% risk of hematoperitoneum 25% risk of hematoperitoneum 2° to rupture of ° to rupture of EP following MTXEP following MTX

MTX 50mg/mMTX 50mg/m² body surface area ² body surface area (~1mg/kg) given IV or IM(~1mg/kg) given IV or IM

Methotrexate Protocol – Methotrexate Protocol – cont’dcont’d

Pt F/U Pt F/U repeat serum quantitative repeat serum quantitative -hCG in 3-4 -hCG in 3-4

days, 7days, then weekly until < 10 IU/Ldays, 7days, then weekly until < 10 IU/L If > day-4 level at day-7 If > day-4 level at day-7 repeat MTX repeat MTX If If -hCG fails to fall by at least 25%/week -hCG fails to fall by at least 25%/week

at any timeat any time repeat dose repeat dose U/S not required routinelyU/S not required routinely

Pt should avoidPt should avoid Alcohol use, sexual I/C, oral folic acid (until Alcohol use, sexual I/C, oral folic acid (until

HCG levels are neg)HCG levels are neg)

Methotrexate Protocol – Methotrexate Protocol – cont’dcont’d

What to expectWhat to expect Majority experience some degree of abd Majority experience some degree of abd

pain (occurs in ~ 50% at day-6)pain (occurs in ~ 50% at day-6) Shedding of a decidual castShedding of a decidual cast Moderate vaginal bleedingModerate vaginal bleeding

Side effects (usually at higher doses)Side effects (usually at higher doses) Impaired liver function, bone marrow Impaired liver function, bone marrow

suppression, neutropenia, stomatitis, suppression, neutropenia, stomatitis, hematosalpinxhematosalpinx

Expectant Mx of EPExpectant Mx of EP

Anticipates spontaneous regression of EPAnticipates spontaneous regression of EP Occurs in ~ 57%Occurs in ~ 57% Symptoms, HCG titers, & U/S findings Symptoms, HCG titers, & U/S findings

followedfollowed Risk of tubal rupture is 10% if HCG levels < Risk of tubal rupture is 10% if HCG levels <

10001000 Criteria includeCriteria include

Sonographic diameter < 3cmSonographic diameter < 3cm Initial Initial -hCG < 1 000 IU/ml, no -hCG < 1 000 IU/ml, no in 2-day in 2-day

period, subsequent levels period, subsequent levels asymptomaticasymptomatic

Future Fertility following Future Fertility following EPEP

Subsequent conception rate is ~ 60%Subsequent conception rate is ~ 60% Incidence of recurrent EP is 15%Incidence of recurrent EP is 15% Other factors influencing include:Other factors influencing include:

Age, parity, history of infertility, Age, parity, history of infertility, evidence of contralateral tubal disease, evidence of contralateral tubal disease, ruptured EP, IUCD use, salpingitisruptured EP, IUCD use, salpingitis

No difference b/t laparoscopy vs No difference b/t laparoscopy vs laparotomylaparotomy

Prevention of EPPrevention of EP

Treat salpingitis early & correctlyTreat salpingitis early & correctly MTX management lowers rate of MTX management lowers rate of

subsequent EPsubsequent EP Risk of EP is Risk of EP is with all methods of with all methods of

contraception, except progesterone contraception, except progesterone containing IUCDscontaining IUCDs

Remember Rh SensitizationRemember Rh Sensitization Rhogam for the Rh-neg womanRhogam for the Rh-neg woman