Diagnosis _ treatment of ectopic pregnancy

							Diagnosis & Treatment
 of Ectopic Pregnancy

      新光吳火獅紀念醫院
         婦產科
                  Introduction
 Ectopic pregnancy is a major concern for women of
  reproductive age.
 Although the fallopian tube is the most common site, it
  can develop in cervix, ovary, and the peritoneal cavity.
  Each one of the atypical locations has unique diagnostic
  and therapeutic challenges.
 Hemodynamically stable patients are now usually
  diagnosed using a combination of transvaginal ultrasound
  and -hCG..
 The option to treat these patients medically or even by
  simple observation and monitoring has become available
Diagnosis of ectopic pregnancy
   Symptoms and signs
   Culdocentesis
   Sonography
   Serum ß-hCG
   Serum preogesteron
   Surgical diagnosis
    – Dilatation and curretage
    – Laparoscope
        Symptoms and signs
 Traditionally, the diagnosis of ectopic
  pregnancy was made based on the clinical
  pictures: symptoms and physical signs.
 The classical presentation of a woman with
  vaginal bleeding, unilateral lower
  abdominal pain, and ipsilateral adnexal
  tenderness mass still can be frequently
  seen.
              Culdocentesis
 The sensitivity and specificity in detecting
  hemoperitoneum was 85-90%.
 Hemoperitoneum in a women with a positive
  pregnancy test is ectopic pregnancy, ruptured
  ovarian cyst, spontaneous abortion.
 The use of ultrasound can quickly and painlessly
  confirm the presence of fluid in the abdominal
  cavity, thus eliminating the need for performing
  culdocentesis
    Transvaginal Ultrasound (I)
 Reliably detects intrauterine gestations as early as
  1 week after missed menses
 Frates et al (1995):
   – The detection of any non-cystic extraovarian adnexal
       mass, living ectopic pregnancy, complex cystic or
       solid masses
   –   Specific for ectopic pregnancy of 98.9%
   –   Positive predictive value of 96.3%
   –   Sensitivity of 84.4%
   –   Negative predictive value of 94.8%
   Transvaginal Ultrasound (II)
 Pitfall in Transvaginal Ultrasound
   – Tubal mass is small or obscured by bowel
   – Pseudogestational sac
   – Corpus luteum as tubal mass
  Transvaginal Ultrasound (III)
 Endometrial thickness
  – The thickness of the endometrial echo complex alone
      may be predictive of a pregnancy.
  –   Spandorfer et al (Fertil Steril, 1996)
  –    In ectopic pregnancy, the mean thickness of the
      endometrial echo complex was 5.95+/-0.35 mm, and
      none of these women was greater than 13 mm.
  –   An intrauterine pregnancy: 13.42 +/- 0.68 mm
  –   spontaneous abortion: 9.28 +/- 0.88 mm
  –   97% of pregnancies:endometrial thickness <= 8 mm
      were abnormal (EP or spontaneous abortion).
            Serum ß-hCG (I)
 Serum ß-hCG is correlated to trophoblastic
  activity.
 Normal increase of the ß-hCG level
   – > 66% in 48 hours
   – >114%~ 172% in 72 hours
 Approximately 15% of intrauterine pregnancies
  will have a <66% rise in ß-hCG level and 13% of
  ectopic pregnancies will have a >66% rise.
            (Kadar et al, Obstet Gynecol 58:162, 1981)
           Serum ß-hCG (II)
 Serum ß-hCG doubling time
  – Normal pregnancy: 1.5 day
  – Tubal pregnancy: 7.7 days
                       (Obstet Gynecol 75:421,1990)


 Falling serum ß-hCG  nonviable pregnancy.
  – If ß-hCG half life >7 days  86% were EP
  – If ß-hCG half life <1.5 days  only 7.6% were EP
                                     (Fertility & Sterility, 1988)
 Combined transvaginal ultrasound
     and Serum ß-hCG (I)
 Reliably detects intrauterine gestations as
  early as 1 week after missed menses
  (-hCG > 1,500; 5-6 weeks’ gestation)
 When the -hCG concentrations was 1500
  IU/L or higher, an empty uterus on
  ultrasonography identified ectopic
  pregnancy with 100% accuracy
        Barnhart and colleagues (Obstet Gynecol, 1994)
 Combined transvaginal ultrasound
     and Serum ß-hCG (II)
 Relationship of gestational age, ß-hCG level,
  and transvaginal ultrasound
 Combined transvaginal ultrasound
     and Serum ß-hCG (III)
 Diagnosing suspected ectopic pregnancy: ß-hCG
  monitoring and transvaginal ultrasound lead the way
 Early screening of high-risk, symptom-free can avert
  tubal rupture, hemorrhage, and the need for emergency
  care
 These benefits of aggressive diagnosis outweigh the
  disadvantages of a false-positive rate of 1.2%
          Serum progesterone
 A value exceeding 25 ng/ml excludes ectopic
  pregnancy with 97.5% sensitivity.
                      (Lipscomb et al, N Eng J M 1999 )
 Values less than 5 ng/ml suggest that the fetus-
  embryo is dead, but not its location.
 Values between 5 and 25 ng/ml –unfortunately
  common – are inconclusive.
                          (McCord et al, Fertil Steril, 1996)
          Surgical diagnosis
 Dilatation and Curretage
  – Differentiate between a non-viable intrauterine
    pregnancy and an ectopic pregnancy if other
    diagnostic findings are inconclusive.
 Laparoscopy
  – Gold standard in the diagnosis of ectopic
    pregnancy and it enables surgical treatment
Ectopic pregnancy diagnostic algorithm
Treatment of ectopic pregnancy
 Surgical treatment
   – Conservative surgery
   – Radical surgery
   – Laparotomy
 Medical treatment
   – Variable dose
   – Single dose
   – Local injection
 Expectant management
          Surgical treatment
 Indication
  – Rupture
  – Diameter > 4.0 cm
  – Pain persisting > 24 hours
  – Laparoscopy needed for diagnosis
  – Suspected heterotopic pregnancy
             Surgical treatment
 Conservative Procedure
   – Salpingostomy – ampulla
   – Segmental resection then anastomosis– isthmus
   – Fimbrial expression (milking) – aborting through
       fimbria
 Radical surgery (salpingectomy)
   –   Uncontrollable bleeding
   –   Extensive tubal damage
   –   Recurrent pregnancy in the same tube
   –   Sterilization
          Surgical treatment
 Laparotomy:
  – Hemodynamic instability
  – Inexperienced surgeon
  – Laparoscopy too difficult
Salpingectomy for tubal pregnancy




1. Electrodesiccation of the tubocornual junction
     Salpingectomy for tubal pregnancy




2. Electrodesiccation and division of the tubo-ovarian ligment
Salpingectomy for tubal pregnancy




3. The tube is excised by the division of the
intervening mesosalpinx
Salpingectomy for tubal pregnancy




4. The tube is removed through an 10 mm cannula
           Linear salpingostomy




1. Injection of dilute vasopressin solution under the
serosa of the mesosalpinx adjacent to the gestational sac
           Linear salpingostomy




2. An incision has been placed over the implantation site
 Linear salpingostomy




3. Gestational products are teased out
Linear salpingostomy




    4. Final inspection
 Persistent ectopic pregnancy of
 conservative surgical treatment
 The most common complication of laparosocpic
  salpingostomy: 5-20%
 Risk factor
   –   Small ectopic pregnancies ( <2 cm diameter)
   –   Early therapy (< 42 days from LMP)
   –   High concentration of ß-hCG ( > 3000 IU/L) pre-op
   –   Implantation medial to the salpingostomy site
 Prophylatic methotrexate       ( Obstet Gynecol 1997;89:118-22)

   – Lower the rate of persistent ectopic pregnancy from
     14.5 % to 1.9%
   – Shorter duration of postoperative monitoring
          Medical treatment
 Methotrexate
  – A folic-acid antagonist, inhibits synthesis of
    purines and pyrimidines, interfering with DNA
    synthesis and cell multiplication
  – Actively proliferating trophoblasts are highly
    vulnerable to methotrexate.
     Methotrexate treatment (I)
 Absolute indication
   – Hemodynamically stable without active bleeding or
     signs of hemoperitoneum
   – Nonlaparoscopic diagnosis
   – Patient can return of follow-up care
   – Patient has no contraindication to methotrexate
 Relative indication
   – Diameter < 3.5 cm in greatest dimension
   – No fetal cardiac motion detected
   – ß-hCG level < 15,000 mIU/ mL
   Methotrexate treatment (II)
 Contraindication
  – Hepatic dysfunciton, SGOT 2 x nl
  – Renal disease, Cr > 1.5 mg/dl
  – Active peptic ulcer disease
  – Blood dyscrasia , WBC < 3,000, PLT <
    100,000
Score for nonsurgical treatment
Score  12: Medical treatment
Score > 12: Surgical treatment




                        (Fernandez et al, Hum Reprod 1991; 6: 995-998)
    Methotrexate-variable dose

 Methotrexate 1 mg/kg intramuscularly, alternate
  days ( days 1,3,5,7)
 Leucovorin 0.1 mg/kg intramuscularly, alternate
  days (days 2,4,6,8)
 Continue until ß-hCG falls > 15% in 48 hours or
  four doses methotrexate given
     Methotrexate-single dose
 Methotrexate 50 mg/m2 intramuscularly
 If < 15% decline in ß-hCG titer between day 4
  and 7, give a second dose of methotrexate
 If > 15 % decline in ß-hCG titer between day 4
  and 7, follow ß-hCG titer weekly until < 10 mIU/
  mL
  Methotrexate-direct injection
 Smaller systemic distribution of the drug
  decreases toxic effects
 Laparoscopic or ultrasound needle guidance is
  needed.
 Rates of successful treatment are lower than with
  systemic methotrexate
 This approach thus offers no advantage over
  systemic methotrexate
   Side effects of methotrexate
 Drug side effect
  – Nausea, vomiting, diarrhea
  – Stomatitis, gastric distress
  – Dizziness
  – Severe neutropenia (rare, even 50 mg)
  – Reversible alopecia (rare)
  – Pneumonitis
   Side effects of methotrexate
 Treatment effects
  – Increase in abdominal pain
     • Transient pelvic pain, occurring in 3-7 days, lasting
       4-12h, presumably due to tubal abortion
     • Differential of transient abdominal pain and
       rupture of ectopic is difficult, surgical intervention
       when there is orthostatic hypotension
  – Increase in ß-hCG levels during first 1-3 days
  – Vaginal bleeding or spotting
       Expectant management
 Many ectopic pregnancies resolve spontaneously.
 Fourteen studies have reported on expectant
  management of ectopic pregnancy. 425 (68%) of
  the 628 ectopic pregnancies resolved without
  surgery.
 ß-hCG concentrations
   – < 1000 IU/L, 88% resolve spontaneously
   – < 2000 IU/L, expectant management resulted in only a
     60% success rate.
    Outcome of conservative
treatment for ectopic pregnancy

                         Successful     Tubal       Intrauterine   Recurrent
                         resolution   patent rate    pregnancy      ectopic
      Method                                                       pregnancy
   Conservative LSC        93%          76%            57%           13%
  Variable-dose MTX        93%          75%            58%           7%
   Single-dose MTX         87%          81%            61%           8%

  Direct injection MTX     76%          80%            57%           6%

 Expectant management      68%          76%            86%           7%



                                                     Lancet Vol 351 April 1998
Fertility after organ-preserving surgery
         of ectopic pregnancy(I)
 Objective:
   – To evaluate the postoperative fertility rate after
     ectopic pregnancy and compare the impact of different
     surgical techniques
 Prospective, 1025 ectopic pregnancies enrolled
   – Both tubes patent (ipsilateral salpingostomy or milk-
     out)
   – Only contralateral tube patent ( ipsilateral wedge
     resection)
   – Only ipsilateral tube patent ( ipsilateral salpingostomy
     or milk-out and contralateral lacking or blocks)
                                        Fertility and sterility 1997
Fertility after organ-preserving surgery
        of ectopic pregnancy(II)
 The pregnancy rate (PR)was similar after wedge
  resection (45.9%) and salpingostomy (42%). The
  recurrence rates did not differ between both
  groups (7.5% vs. 8.2%)
 In blocked or absent group contralateral tube , the
  PR was poor (31.2%) and recurrent EP was high
  ( 16.0%), indicating that most pregnancies are
  achieved through the contralateral tube.
                                  Fertility and sterility 1997
Fertility after organ-preserving surgery
        of ectopic pregnancy(III)





                           Fertility and sterility 1997
Fertility after organ-preserving surgery
        of ectopic pregnancy(IV)
 Conclusion
  – The postoperative fertility rate after an EP is
    reduced.
  – The type of surgery usually has no significant
    impact.
  – In the case of a blocked or absent contralateral
    tube, the patient must be informed about the
    significantly reduced fertility rate and the
    elevated risk for EP recurrence.
                                 Fertility and sterility 1997
  Current status of surgical and
  nonsurgical management (I)
 There is no difference in the reproductive
  outcome after treatment of EP by laparotomy and
  by laparoscopy.
 The rate of persistent EP after conservative
  surgery ranges from 3% to 20 %
 Salpingostomy
   – IUP( 61%), recurrent EP(15.5%)
 Salpingectomy
   – IUP ( 38.1 %), recurrent EP ( 9.8%)

                            Mylene et al. Fertil & Steril, 1997
  Current status of surgical and
  nonsurgical management (II)
 Single-dose methotrexate
   – 84% did not further treatment
   – 54% had subsequent IUP
   – 8% recurrent EP
 Salpingostomy is associated with higher
  subsequent intrauterine pregnancy and recurrent
  EP rates compared with salpingectomy.
 Methotrexate is a viable alternative to
  laparoscopic salpingostomy for a selected group
  of patients.
                            Mylene et al. Fertil & Steril, 1997
  Fertility analysis after ectopic
           pregnancy (I)
 Patients: 328 ectopic pregnancies and then try to
  become pregnant
 Results:
   – 215 (65.5%) became pregnant after a mean of 5
     months
   – 182 ( 84.7%): intrauterine pregnancy
   – 22(10.2%): recurrent pregnancy
   – Cumulative intrauterine pregnancy rate
      • 56 % at one year and 67 % at 2 year


                                   • Anne et al. Fertil & Steril, 2001
  Fertility analysis after ectopic
           pregnancy(II)

 Fertility depends on preexisting maternal
  characteristics of the women (age, tubal damage,
  and infertility) rather than type of treatment of EP.
 However, conservative treatment seems to be
  slightly but not significantly more effective than
  radical treatment.

                             • Anne et al. Fertil & Steril, 2001
              Conclusion (I)
 The combination of serum [beta]-hCG and
  transvaginal ultrasonography remain the best
  available resources for the diagnosis of ectopic
  pregnancy in hemodynamically stable patients.
 There is no consensus on which treatment is
  more effective, minimizing the risk of persistent
  ectopic pregnancy, while providing the optimum
  future fertility potential.
              Conclusion (II)

 Fertility rates are comparable in patients treated
  with salpingostomy and systemic methotrexate
 In carefully selected patients, methotrexate is a
  successful alternative to surgical treatment
  removes the surgeon’s skill as a variable to affect
  future fertility, and offers the potential
  considerable cost saving
 Early diagnosis has made ectopic pregnancy
  seems to be a medical disorder.
   Non tubal ectopic pregnancy
 Non tubal ectopic pregnancy is a rare event. Due
  to the infrequency of this condition,
  standardization in diagnosis and management is
  complex
 Interstitial pregnancy
 Cervical pregnancy
 Ovarian pregnancy
 Abdominal pregnancy
 Heterotopic pregnancy
        Interstitial pregnancy
 Sonographic image
  – A gestational sac located within the
    myometrium but detached from the
    endometrial echo complex
 Lau and Tulandi ( Fertil Steril 1999 )
  – Conservative surgically or with or local
    methotrexate injection
  – The success rate was 83%
       Cervical pregnancy(I)
 Sonographic image
  – Cystic structure with a central ring consistent
    with a yolk sac in the cervix
  – Color doppler imaging revealed an extensive
    blood supply to the sac
  – Low impedance of the peritrophoblastic flow
    on pulsed Doppler.
  – Hourglass uterine shape
       Cervical pregnancy(II)
Management





    From: Ushakov: Obstet Gynecol Surv, Volume 52(1).January 1997.45-59
        Cervical pregnancy(III)
 Outcome of post cervical pregnancy




 From: Ushakov: Obstet Gynecol Surv, Volume 52(1).January 1997.45-59
         Ovarian pregnancy
 Diagnosis
  – ultrasound scan report, that, together with the
    values of the ß-hCG , allowed us to formulate
    a diagnosis lately confirmed by the
    laparoscopy.
 Management
  – laparotomic ovariectomy,
  – laparoscopy
  – medical management
      Heterotopic pregnancy
 Rare in spontaneous pregnancies but 1-3 %
  following ART
 Difficult to diagnose after superovulatory
  drugs because of multiple ovum formation
 Ultrasonography detects only half of the
  heterotopic pregnancies
 Requires surgical treatment