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Sites of resection
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in mesosalpinx
Management of the Ectopic Pregnancy — 227
D
Interceed
E
Figure 9.4.6. (Continued )(D) The resected segments and mesosalpinx are seen. (E) Interceedis placed over the
coagulated surfaces.
228 — Bulent Berker, Ceana Nezhat, Farr Nezhat, and Camran Nezhat
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Atraumatic
grasping forceps
Fallopian
tube
Ectopic pregnancy,
hydrosalpinx or
hematosalpinx
Round
ligament
Bipolar electrocoagulation
forceps
Coagulation at
isthmus of
fallopian tube
Mesosalpinx
A
Figure 9.4.7. (A) Total salpingectomy is done by progressively coagulating and cutting the mesosalpinx, beginning with the isthmic segment. (Continued )
FOLLOW-UP
In 1 week, the patient returns for a serum hCG to ascertain
resolution of the ectopic gestation. The hCG level should be
undetectable or very low. If it is above 20 IU/L, a repeat blood
test is ordered 1 to 2 weeks later, when the hCG should be
undetectable.[71] If the levels persist, other treatment options
must be considered.
INTERSTITIAL PREGNANCY
Interstitial (cornual) pregnancies occur rarely; the prevalence
ranges from one in 2500 to one in 5000 live births. Because the
morbidity and mortality are high, the correct diagnosis must be
made and treatment must begin promptly. This type of EUP is
associated with an increased risk of traumatic rupture and hemorrhagic shock, with a mortality rate of 2% to 2.5%. Later diagnosis and the increased vascularity of this area account for these
increased risks. Two percent to 4% of ectopic gestations are interstitial. The anatomy favors the growing gestation, accounting for
the late onset of symptoms and occasional reports of term interstitial pregnancies. The traditional management for interstitial
(cornual) pregnancy is salpingectomy with or without cornual
resection and sometimes hysterectomy. In selected women, more
conservative and lessradical approaches are employed if thediagnosis is madeearlyand the patient isstable. Other options include
methotrexate (MTX) injections (local or systemic), potassium
chloride injections (local), and prostaglandin administration. In
a series of 15 patients, unruptured interstitial pregnancies were
managed with local MTXadministration of1 mg/kgbody weight
under transvaginal ultrasound or laparoscopy.[72]
Interstitial pregnancy is suspectedinwomenwith an enlarged
asymmetric uterus and an eccentrically placed gestational sac on
sonography. Differential diagnoses include ovarian and abdominal pregnancy and a pregnancy in one horn of a bicornuate
uterus. The diagnosis is confirmed by laparoscopy, and the treatment involvesimmediatelaparotomyoracombined laparoscopic
and hysteroscopic approach in certain patients.
At laparoscopy, the interstitial pregnancy is recognized as a
cornual bulge stretching the myometrium and serosal surface
(Figure 9.4.9). If the overlying myometrium is thick and intact,
removal of the pregnancy by hysteroscopy is preferable. Early
detection of an interstitial pregnancy can be managed by combining MTX and hysteroscopy.[73] A diagnostic laparoscopy is
done to identify the location and accessibility of the gestation. If
it is accessible by hysteroscopy, it is suctioned or resected using
Atraumatic
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grasping forceps
Management of the Ectopic Pregnancy — 229
Isthmus of
fallopian tube
Bipolar electrocoagulation
forceps
Mesosalpinx
B
Ectopic
pregnancy
Bipolar electrocoagulation
forceps
Ovary
Uterus
Tubo ovarian
C
ligament
Figure 9.4.7. (Continued )(B) The mesosalpinx is coagulated with bipolar forceps. (C) The procedure is con-
tinued. (Continued )
230 — Bulent Berker, Ceana Nezhat, Farr Nezhat, and Camran Nezhat
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CO2 laser
Scissors
D
Interceed
E
Figure 9.4.7. (Continued )(D) The tube is separated from the uterus by using bipolar coagulation and scissors
or the laser (inset). The isolated tubal segment is removed intact or in sections through the 10-mm sleeve.
(E) Interceed may be placed over the resected area to prevent postoperative adnexal adhesions.
Management of the Ectopic Pregnancy — 231
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Endopouch being pulled
through 10-mm sleeve
Figure 9.4.8. The resected tube containing the pregnancy is placed in an Endopouch. The inset shows removal
through a 10-mm trocar sleeve.
forceps, scissors, or electrosurgery under hysteroscopic control.
For larger pregnancies, it is better and faster to do a gentle curettage of the dilated interstitial–cornual area under laparoscopic
control. To verify complete removal of the products of conception, hysteroscopic observation of the curetted cornu and the
interstitial area is done.
Cornual
(interstitial)
If the pregnancy has eroded through the cornual
myometrium, it is prudent to do a laparotomy to remove the
pregnancy. In some patients, a laparoscopic approach is considered after the patient is counseled concerning the possibility of a
laparotomy.[74–76] The cornu is vascular, and profuse bleeding
may occur quickly..
Figure 9.4.9. An interstitial pregnancy is recognized as a cornual bulge in the myometrium and serosal surface.
232 — Bulent Berker, Ceana Nezhat, Farr Nezhat, and Camran Nezhat
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NONSURGICAL MANAGEMENT
Expectant Management
Other approaches to tubal pregnancy include expectant management and MTX. Because some tubal pregnancies end in tubal
abortions orcomplete reabsorption, particular patients aremonitored with repeated levels of hCG until tubal abortion or reabsorption occursas suggested by fallinghormonal levels.[77] With
declining values and a starting hCGabove2000IU/L,93.3%failed
on expectant management, whereas below 2000 IU/L, 60.0%
succeeded.[78] This choice preserves tubal function and fertility, but tubal occlusion can result from retained products of
conception.[79] Shalev and coworkers [78] found no difference
in the resultant ipsilateral tubal patency or 1-year fertility rates of
women succeeding or failing on expectant management. Rantala
and Makinen [80] reported a pregnancy rate of 88% and a rate
of repeat ectopic pregnancy of 4.2%. Patients who were treated
expectantly had agoodfertility outcome. Spontaneous regression
of the EUP did not lead to increased tubal damage because of the
risk for a repeat EUP.
Although ectopic pregnancy may resolve spontaneously
through regression or tubal abortion, about 90% of women with
ectopic pregnancy and serum β-hCG levels greater than 2000
IU/L require operative intervention owing to increasing symptoms or tubal rupture.[1] Tubal rupture also may occur when
serum β-hCGlevelsarelowordeclining,orboth. Expectant management should be offered only when transvaginal ultrasonography fails to show the location of the gestational sac and the
serum levels of β-hCG and progesterone are low and declining.
Because of the possibility of tubal rupture, these patients must be
carefully monitored until the serum β -hCG concentration falls
below 15 IU/L; at thispoint,almostallectopic pregnancies resolve
spontaneously, without rupture.
The overallefficacyofexpectantmanagementwas69.2%in10
prospective studies.[2] Banerjee et al. [81] followed 135 women
with an unknown location of their pregnancy. Complete data
sets were obtained in 127 cases. These included 34 (27%) normal IUPs, 11 (9%) miscarriages, and 18 (14%) EUPs. A total of
64 pregnancies (50%) resolved spontaneously. These data show
that most pregnancies of unknown location are abnormal and
many resolve spontaneously. The role of expectant management
in those with known EUP is limited because of its risks compared with the high efficacy and accessibility of MTX or surgical
treatment.[2] The difficulty with such management lies in the
selection of the proper patients. A patient with low or falling
titers must understand the risks involved and have the ability to
comply with instructions concerning follow-up.
Medical Treatment
Treatment with MTX is an alternative to surgery in up to a
quarter of women with unruptured ectopic pregnancy. MTX has
been recommended for women with a cornual pregnancy or an
incomplete resolution of surgically treated ectopic gestation and
for residual trophoblastic tissue. MTX, a folic acid antagonist,
inhibits DNA synthesis in actively dividing cells, including trophoblasts. Patients who are poor risks because of induced ovarian hyperstimulation syndrome and those suspected of having
extensive intraperitoneal abdominal adhesions may be treated
medically if they are hemodynamically stable.
Two regimens are commonly used for the systemic administration of MTX. The first involves administration of MTX and
leucovorin on alternate days until β -hCG concentrations begin
to drop. This regimen has a success rate (defined as avoidance
of surgery) of 93%.[82–84] The second regimen involves administration of a single dose of MTX, followed by repeated doses a
week apart if β-hCG concentrations do not fall by 15% between
days 4 and 7. As reported by Lipscomb et. al., more than 90% of
women treated with the second regimen avoided surgery.[85]The
criteria for MTX treatment of ectopic pregnancy are as follows:
hemodynamic stability, ability and willingness of the patient to
comply with posttreatment monitoring, pretreatment serum β-
hCG concentration less than 5000 IU/L, and absence of ultrasound evidence of fetal cardiac activity.[1] In one study, patients
were treated with MTX 1 mg/kg intravenously and leucovorin
0.1 mg/kg intramuscularly every other day for 4 days. These
patients were admitted to the hospital and monitored during
therapy with serum levels of aspartate aminotransferase, lactate
dehydrogenase, hCG, and progesterone and with complete blood
counts and platelet counts.[86] A single intramuscular injection
of MTX (50 mg/m
2
) without citrovorum rescue was used in 29
of 30 consecutive patients with unruptured ectopic pregnancies.
Six patients experienced an increase in abdominal pain, and two
were hospitalized for overnight observation.[87] Thissingle-dose
plan administered on an outpatient basis decreases the expense
and lessens the side effects associated with the treatment of EUPs
3 to 5 cm or less in diameter.
One randomized controlled trial has been done to compare single-dose and multiple-dose regimens of MTX.[88] Fiftyone women with a presumed ectopic pregnancy were randomly
assigned single-dose or multiple-doseMTX. The β-hCG concentration for inclusion was less than 10,000 IU/L. Single-dose MTX
was successful in 90%andmultiple-dosein 86% of women.There
was no evidence of a difference in median time to resolution and
no difference in adverse events between regimens. The efficacies of single- and multiple-dose regimens were recently compared in a meta-analysis of all available studies.[82] This metaanalysis of 26 studies included 267 women receiving a multipledose treatment and 1067 treated with single-dose therapy. The
success rates (defined as not requiring surgery) were 88.1% for
single-dose therapy and 92.7% for multiple-dosetherapy, butthe
chances of failure were greater with single-dose therapy. Importantly, this difference was much more marked when results were
adjusted for serum hCG values and the presence of fetal cardiac activity. Side effects were lower with single-dose therapy.
Among women who were due to receive a single dose, 13.6%
required two or more doses. These results suggest that it may be
time to reevaluate the role of multiple-dose therapy in selected
women.
Patients treated with MTX should be followed closely. The
serum β-hCG concentration should be measured weekly. It is
not unusual to see an increase in serum hCG levels in the following 3 days and mild abdominal pain of short duration (1 to
2 days). However, the pain may also be severe, perhaps as a result
of tubal abortion or the formation of hematoma with tubal distention. Severe abdominal pain, however, may be a sign of actual
or impending tubal rupture. If the serum β-hCG concentration
has not declined by at least 25% 1 week after MTX administration, a second dose should be given. In general, a second dose is
needed in 15% to 20% of patients.[82,89]
Management of the Ectopic Pregnancy — 233
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Use of mifepristone as an adjunctive treatment to MTX for
ectopic pregnancy has been assessed in two randomized controlled trials. Although results of initial pilot studies seemed
promising [90], those of a subsequent multicenter randomized trial noted no benefit of the combined regimen over MTX
alone.[91] In the second trial [92], involving 50 women, both
treatment approaches were successful, but only one of 25 women
in the mifepristone and MTX group needed a second dose of
MTX, whereas in the MTX-only group, four of 25 needed a second dose. The time to resolve the unruptured ectopic pregnancy
was also significantly faster in the group who received combination mifepristone and MTX.[92] Further studies are needed to
consider the role and cost of mifepristone in combination with
MTX.
Injection of MTX into the gestational sac under ultrasound
guidance or at laparoscopy is feasible, and 17 of 24 patients
were treated successfully with this technique.[93] Seven of those
patients required additional systemic injections, and one patient
experienced tubal rupture 3 days after the initial injection. The
tubal injection consisted of 10 to 20 mL of adrenaline 1:80,000
dilution injected into the mesosalpinx with a 22-gauge needle,
followed by 100 mg MTX injected into the tubal gestation. Leucovorin 15 mg was given orally 30 hours after the administration
of MTX. Subsequent systemic MTX injections were given intramuscularly,50 mgevery2to4days,according to the level of serum
hCG. The relative efficacies of MTX and prostaglandin sulprostone (Nalador, Schering Laboratory, Lys-Lez-Lannoy, France)
have been compared.[94] The medication was administered into
the gestational sac and intramuscularly on days 3, 5, and 7 after
the day ofdiagnosis in 21patients with anunruptured tubal pregnancy. Both therapies were effective. However, 34% of patients
underwent either laparotomy or laparoscopy for a ruptured tubal
pregnancy ora persistent risein hCG levels despite the treatment.
Local injection of MTX requires a sonographically visible
EUP as well as technical skills and has less consistent success rates
than does systemic MTX therapy.[95] Although local administration of MTX may be associated with a lower incidence of side
effects, its administration is associated with more inconvenience
to the patient and the medical staff.[96]
The route of MTX administration has also been recently
revisited. Most recent case series have reported on intramuscular
rather than local ultrasound-guided MTX administration, and
there is a wide variation in reported success rates.[66,97] No
randomized trial comparing route of administration has been
undertaken, but in a review of 137 women treated by either
intramuscular (50 mg/m
2
) or local ultrasound-guided administration (1 mg/kg), the overall success rate was 67.1% and 92.5%
in the two groups.[98] Multivariate analysis confirmed a higher
success rate with locally administered MTX. The practicality of
local treatment by laparoscopy is questionable. Local injection
under laparoscopic guidance offers no advantageoverultrasound
guidance because the women must undergo a laparoscopy if the
medical treatment fails. It is more invasive than systemic MTX
treatment, and the ectopic gestation can be removed easily during the laparoscopy.[65] Laparoscopy should now be performed
to provide definitive treatment, which is removal of the ectopic
pregnancy.
Outcomes of systemic MTX treatment have been similar to
those of laparoscopic salpingotomy with respect to success rate,
tubal patency, and the reproductive outcome. In a prospective
randomized study of systemic MTX versus laparoscopic salpingostomy, Hajenius et al. [83] found a success rate of 82% after
MTX treatment and 72% after salpingostomy. Unilateral tubal
patency was 55% and 59%, respectively. It is important to note
that the surgical approach can be done universally for all patients
with ectopic pregnancy,whereasMTX treatment is given only to a
selected group of patients. The two treatments can complement
each other. The advantages of single systemic MTX compared
with laparoscopic salpingostomy are noninvasiveness, avoidance
of therisk of general anesthesia and surgery, shorter hospital stay,
and lower cost.
Medical treatment of EUP with MTX has become the standard of care in manyareas of the United States. However, patients
with an EUP treated withMTX may require anemergency operation for rupture.[99] Systemic MTX therapy had a more negative
impact on patients’ health-related quality of life than did laparoscopic salpingostomy.[100] This negative impact on patients’
health-related quality of life of systemic MTX therapy should
be taken into account in deciding on the appropriate therapy for
a tubal pregnancy. Systemic MTX therapy would be preferred by
most patients as part of a completely nonsurgical management
strategy.[95]
Laparoscopy was as effective as laparotomy in the treatment
of tubal pregnancy and reduced the cost considerably.[101,102]
Amongstablepatients,laparoscopicexcisionofEUPssavednearly
25% of hospital cost per case compared with laparotomy.[103]
Hemodynamic instability increased the cost of management
because of the longer length of stay and higher laboratory costs.
The cost savings may be lost if patients undergoing laparotomy
are dischargedon or before postoperative day 2 or if laparoscopic
treatment of the EUP is not associated with rapid postoperative
discharge.[104]
Medical treatment with MTXis supposed to offer costsavings
by minimizing hospitalization.[105,106] Follow-up of patients
receiving MTX often is prolonged, necessitatingadditional blood
tests, repeat sonographic evaluations, and loss of days from work.
However, afinancialanalysisofEUP management at a large health
plan revealed that total charges were similar for laparotomy and
laparoscopy($6720and$6840),whereasoutpatientMTXtherapy
cost less than the two surgical procedures (average of $818 per
case, P ≤ 0.001).[107] Another economic analysis described the
possible cost benefits of conservative tubal operations for EUP
over salpingectomy.[108] In another study, Mol et al. [109] also
found that systemic MTX was less costly than laparoscopy in
women with initial serum hCG levels of less than 1500 IU/L.
However, in women whose initial hCG levels were greater than
3000 IU/L, methotrexate treatment was more expensive.
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