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Management of the Ectopic Pregnancy — 217
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Table 9.4.2: Symptoms andSignsSuggestingTubal Pregnancy
Nausea, breast fullness, fatigue, interruption of menses
Lower abdominal pain, heavy cramping, shoulder pain
Uterine bleeding, spotting
Pelvic tenderness; enlarged, soft uterus
Adnexal mass, tenderness
Positive pregnancy test
Serum hCG levels ≤6000 IU/L at 6 weeks
Less than 66% increase in hCG titers in 48 hours
Positive culdocentesis (83%)
Absence of gestational sac in the uterus by TVS
Gestational sac outside the uterus by TVS
DIAGNOSIS
Symptoms
The usual pregnancy symptoms, including nausea, vomiting,
breast fullness, fatigue, and interruption of the normal menstrual
pattern, also occur with tubal pregnancies. Othersymptomsmore
typical of EUP include lower abdominal pain of varying intensity and abnormal uterine bleeding ranging from amenorrhea to
spotting or heavy bleeding. The presence of shoulder pain suggests possiblerupture, with intraperitoneal blood flowingtoward
the diaphragm causing phrenic nerve irritation.
Physical Findings
Fever of more than 101◦F is unusual. About one third of patients
with ruptured tubal pregnancies experience syncope because of
hypotension caused by hypovolemia. Signs of ectopic pregnancy,
including lower abdominal tenderness with or without rebound,
are more severe on the affected side. There may be tenderness
with cervical motion. The uterus usually is enlarged and soft. An
adnexal mass is present in 50% of these patients (Table 9.4.2).
Patients with abdominal peritoneal signs or definite cervical
motion tenderness constitute a high-risk group, whereas patients
with only midline menstrual-like cramping constitute a low-risk
group.[26] Abdominal pain, rebound tenderness on abdominal
examination, fluid in the pouch of Douglas at transvaginal ultrasound examination, and a low serum hemoglobin level are independent predictors of tubal rupture.[27] Another study discovered no constellation of physical examination findings that could
confirm or exclude the diagnosis reliably.[28] Rebound tenderness and muscular rigidity were associated with a high likelihood
of an EUP, whereas findings on speculum inspection and vaginal
examination contributed little toconfirmthediagnosis. Information provided byphysicalexamination for thediagnosis is limited
compared with that obtained fromtransvaginal sonogram (TVS)
and serum hCG measurements. A pelvic digital examination for
patients with a suspected EUP is of limited value.[29]
Laboratory Studies
The presence of a pregnancy can be discovered as early as 10 days
after ovulation with sensitive serum assays for β -hCG. Isolated
values of hCG can aid in the diagnosis only when used in combination with other diagnostic tests. It is the pattern of the rise and
fall thatis meaningful.Doubling ofthe hCG levels every 48 hours
in the fifth gestationalweekis an indication of anormallygrowing
IUP. However, using thiscriterion, 15% ofnormal IUPs could fall
in the EUP category and 13% of EUPs would be missed. Besides
having lower titers and slower increases in serum concentrations
of hCG compared with normal pregnancies, ectopic pregnancies have slower declines in the hCG titers than do spontaneous
abortions.
If a low serum hCG level (≤1000 IU/L) is associated with a
higher relative risk of ectopic pregnancy, then can very low levels
predict a benign clinical course? In general, no. Although a single
very low serum level (≤100 IU/L) has been felt to be reassuring,
in a review of 716 admitted patients with ectopic pregnancy, 29%
of those with such a level were found to have tubal rupture at
laparoscopy.[30] The risk of tubal rupture was similar across a
wide range of hCG values. Another study identified 38 instances
of rupture among women with serum levels ranging from 10 to
189,720 IU/L.[31]
Ultrasonographic identification of an intrauterine pregnancy
(gestational sac plus yolk sac or other embryonic sign) rules
out ectopic pregnancy in most patients.[32] The exception is
in patients with ovulation induction and assisted conception,
who are at risk of heterotopic pregnancy (dizygotic twins, one
intrauterine andoneextrauterine).Although this phenomenon is
exceedingly rare in the general population (estimated frequency,
one per 3889to 30,000 pregnancies) [33],in the setting ofassisted
reproduction, it may occur in one in 100 pregnancies.[34] Kadar
and colleagues [35] noted that the absence of an intrauterine
gestational sac on abdominal ultrasound and serum β-hCG lev-
els of 6000 to 6500 IU/L suggest an EUP. The presence of an
apparent intrauterine gestational sac with levels below 6500 IU/L
implies anEUP or a missed or spontaneous abortion. More accurate diagnostic studies are obtained with high-frequency vaginal
transducers that can discover a normal gestational sac in 98% of
women after the fifth week of pregnancy, when the hCG levels
are between 1000 IU/L and 1500 IU/L, the so-called discriminatory zone.[36] In one study, the sensitivity of TVS for the
prediction of EUP was 87% and the specificity was 94%.[37]
The positive and negative predictive values were 92.5% and 90%,
respectively. In the absence of an intrauterine sac, ectopic pregnancy is likely when a level of 1500 IU/L is associated with an
adnexal mass or fluid in the pouch of Douglas or in patients
without these clinical findings, with a level of at least 2000
IU/L.[38]
A single progesterone assay is predictive of an abnormal
pregnancy but not specific for an extrauterine one. A value of
25 ng/mL or more suggests a normal IUP. Serum progesterone
values of 15 ng/mL or less imply an abnormal pregnancy, ectopic
pregnancy, or threatened abortion. A meta-analysis incorporating 26 studies evaluating one serum progesterone measurement
for the diagnosis of EUP showed a good discriminative capacity
for the diagnosis of pregnancy failure and that of a viable IUP.
However, one measurement could not discriminate between an
EUP and an IUP.[39]
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Table 9.4.3: Comparative Resultsof Conservative Operations
for Tubal Pregnancy by Laparotomy and Laparoscopy
Cases,
Author(s)
Laparotomy
Vermesh et al. [41]
DeCherney and
Kase [44]
Stromme [47] 45 71 15
Timonen and
Nieminen [48]
Total 364 47.75 14.75
Laparoscopy
DeCherney and
Diamond [43]
Pouly et al. [45] 118 64 22
Vermesh et al. [46]
Total 227 58.67 14.67
∗
Controlled and prospectively randomized to laparotomy and
laparoscopy.
no.
∗
30 42 16
49 40 12
240 38 16
79 62 16
∗
30 50 6
Intrauterine
Pregnancy, %
Tu b al
Pregnancy, %
The ideal marker for ectopic pregnancy would be specific
for tubal damage or present only after endometrial implantation.
Variousmarkershave been assessed,including creatinekinaseand
fetal fibronectin, but none is sufficiently sensitive or specific for
the diagnosis of ectopic pregnancy.[40] Culdocentesis revealing
nonclotting blood is found inmorethan50%ofunrupturedtubal
pregnancies.[41] When it is used in combination with a positive
pregnancy test, positiveculdocentesisresults suggest thepresence
of an EUP.
TREATMENT
Once the diagnosis is made, treatment choices include laparotomy, laparoscopy, chemotherapy, and expectant management.
Hemodynamic instability previously was considered an indication for immediate laparotomy. The availability of optimal anesthesia and advanced cardiovascular monitoring and the ability
to convert rapidly to laparotomy if required enable the safe performance of operative laparoscopy in most women with hypovolemic shock.[42] The superior exposure with laparoscopy
provides the possibility of a rapid diagnosis and control of the
bleeding, making laparoscopy a good choice.
Since 1970, a conservative approach to unruptured EUP has
been advocated to preserve tubal function (Table 9.4.3). Several types of tubal operations have been done successfully.[43]
These operations include linear salpingostomy, “milking” the
pregnancy from the distal ampulla (Figure 9.4.2), and partial salpingectomy followed by anastomosis. Postoperative viable births
or repeat EUPs are similar after salpingectomy with or without ipsilateral oophorectomy and salpingostomy.[44] In 321
tubal pregnancies treated conservatively by laparoscopy, it was
reported that 15 (4.8%) required subsequent laparotomy or a
second laparoscopic procedure as hCG levels failed to return to
normal.[45]
The preferred operative approach is by laparoscopy.[46]
This technique yields pregnancy rates comparable to those
reported after laparotomy.[44–49] This laparoscopic procedure
was proven in prospective randomized trials to be superior to
laparotomy.[50] Vermesh and associates [46] prospectively randomized patients with unruptured EUP to either laparoscopy
or laparotomy. Those authors analyzed postoperative morbidity, length of hospital stay, duration of convalescence, hospital
cost, postoperative tubal patency by hysterosalpingography, and
pregnancy rates. The two proceduresweresimilarlysafeand effective, but the laparoscopic approach was more cost-effective and
required a shorter recovery period. The laparoscopic approach
results in improved fertility rates because of reduced formation
of postoperative adhesions.[51]
A systematic review [52] ofthreerandomizedcontrolledtrials
[53–55] showed that open salpingostomy when compared with
laparoscopic salpingostomy increased rates of elimination of the
tubal pregnancy (2.4% vs. 12.5%), mainly because of the higher
persistent trophoblast rate with laparoscopic surgery. There was
no difference in the subsequent tubal patency or in subsequent
rate of intrauterine pregnancy or repeat ectopic pregnancy, but
perioperative blood loss was higher with open surgery. Further
studies areneeded to establish whether the persistent trophoblast
rate is as high as in the original studies.
Animal [56] and clinical [57] studies confirmed the impression that laparoscopic procedures were associated with reductions of newadhesionsandre-formationofpreexistingadhesions.
Tubal healing and the extent of pelvic adhesions were assessed at
repeat laparoscopy within 15 weeks of the initial operation.[58]
Although tubal patency did not differ between the two groups,
patients who were treated by laparotomy developed more adhesions. Brumsted and coworkers [59] reported a shorter convalescence of 8.7 ± 7.8 days in the laparoscopy group compared with
25.7 ± 16.2 days among the laparotomy patients (P ≤ 0.01) and
reduced postoperative analgesia requirements in the laparoscopy
patients of 0.84 ± 2.3 doses compared with 4.64 ± 2.9 doses
(P ≤ 0.01) in the laparotomy group.
With adequate experience in operative endoscopy and with
proper instruments, most patients with ectopic pregnancies can
be treated successfully by laparoscopy, regardless of the gestation’s
size or location,the number ofgestations, or thepresence of tubal
rupture.[60] At the initial exploratory procedure, both fallopian
tubes are examined to avoid missing multiple ectopic pregnancies. Because of delayed childbearing and the expanded use of
assisted reproductive technology, multiple EUPs may become
more prevalent. After a nonstimulated menstrual cycle, three
separate gestational sacs were identified in one woman at initial operative laparoscopy, one in the right tube and two in the
left tube.[61]
Persistent ectopic pregnancy after laparoscopic salpingostomy arises in 4% to 15% of women.[40] Therefore, β-hCG con-
centrations should be followed until they are undetectable. Risk
factors for persistent ectopic pregnancy are small ectopic pregnancies (≤2 cm), early surgical intervention (≤42 days from last
menstrual period), and β-hCG values of 3000 IU/L or more.
The rate of persistent ectopic pregnancy was reduced in one
study from 14% to 2% with the useof prophylactic methotrexate,
which also reduced the period of postoperative monitoring.[62]
Management of the Ectopic Pregnancy — 219
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Infundibular
(ostial/ fimbrial)
Figure 9.4.2. This infundibular pregnancy is about to be extruded. At laparoscopy, such conditions can be
managed by grasping the tissue and completing the process. Bleeding usually is minimal.[110]
However, to avoid one additional case of persistent trophoblast
after conservative surgery, eight women would need to betreated
with methotrexate. Monitoring of the β -hCG concentrations
would, therefore, seem to be a better option, provided that the
woman is amenable to monitoring.
In the management of a tubalgestation,thegynecologist must
consider the patient’s desire for further childbearing. The patient
is informed of the possibility of laparotomywith salpingectomyor
more extirpative procedures because of uncontrollable bleeding
or unexpected findings. If neither tube is salvageable, the uterus
and at least one ovary is preserved to retain the possibility of in
vitro fertilization.[63]
Laparoscopic Techniques
The location, size, and nature of the tubal pregnancy are established. Ruptured tubal pregnancies are treated successfully endoscopicallyifthebleedinghasceasedorisstoppedadequately. Once
bleeding is controlled, the productsofconceptionand blood clots
are removed. A 10-mm suction instrument cleanses the abdominal cavity quickly. Forced irrigation with lactated Ringer’s solution dislodges clots and trophoblastic tissue from the serosa of
the peritoneal organs with minimal trauma to those structures.
Salpingotomy
For unruptured tubal pregnancies, the tube is identified and
mobilized. To reduce bleeding, a 5- to 7-mL diluted solution
containing 20 units of vasopressin (Pitressin, Monarch Pharmaceuticals) in 100 mL of normal saline is injected with a 20-gauge
spinal or laparoscopic needle in the mesosalpinx just below the
EUP and over the antimesenteric surface of the tubal segment
containing the gestational products (Figure 9.4.3). The needle
must not be within a blood vessel because intravascular injection of vasopressin solution cancauseacutearterial hypertension,
bradycardia, and death.[57]
Using a laser, microelectrode, or scissors, a linear incision is
made on the antimesenteric surface extending 1 to 2 cm over the
thinnest portion of the tube containing the pregnancy. The pregnancy usuallyprotrudes through the incision and slowly slips out
of the tube; it is removed by using hydrodissection or laparoscopic forceps (Figure 9.4.4). Forceful irrigation in the tube’s
opening can dislodge the gestation from its implantation. As
the pregnancy is pulled out or extrudes from the tube, some
products of conception may adhere to the implantation site by a
ligamentous structure containing blood vessels. Using the electrocoagulator, this structure is coagulated before the tissue is
removed. Oozing from the tube is common but usually ceases
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Ampullary
A
Incision site
Ampullary
Pitressin injected
into mesosalpinx
and top of ectopic
B
Figure 9.4.3. (A) An unruptured ampullary pregnancy. (B) Injection is done into the top of the tube (inset) and
into the mesosalpinx with 5 to 7 mL of diluted Pitressin.
CO2 laser
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opening
fallopian tube
Management of the Ectopic Pregnancy — 221
Knife electrode
opening fallopian
tube
A
Hydrodissection to
dislodge and remove
the products of
conception
B
Figure 9.4.4. (A) The pregnancy is revealed by either a CO2laser or knife electrode (inset) after a tubal incision
is made. (B) Products of conception are being separated from the tube. (Continued )
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Removal of ectopic pregnancy with
grasping forceps through 10-mm sleeve
The tubal incision is left open
to heal by secondary intention
C
Interceed
D
Figure 9.4.4. (Continued )(C) Depending on the size of the pregnancy, the products of conception can be
removed through a 5- or 10-mm trocar sleeve (inset). The tubal incision is not sutured and usually heals
spontaneously. (D) In some instances, the incision may be covered with Interceed.
Isthmic
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Management of the Ectopic Pregnancy — 223
A
Figure 9.4.5. (A) An isthmic pregnancy is illustrated. (Continued )
spontaneously.Occasionally,coagulationisnecessarywith a defocused laser beam or an electrocoagulator. Depending on the size,
the products of conception are removed through a 5- or 10-mm
trocar sleeve.
Tubal Resection
Resection of the tubal segment that contains the gestation is
preferabletosalpingotomyforan isthmicpregnancyora ruptured
tube or if hemostasis is difficult to obtain. Segmental resection is
done with bipolar electrosurgery, fiber lasers (potassium titanyl
phosphate, argon, or Nd:YAG), CO
laser, sutures, or stapling
2
devices.
Bloodless segmental resection is achieved by grasping the
proximal and distal boundaries of the tubal segment containing the gestation with a Kleppinger forceps and coagulating them
from the antimesenteric surface tothe mesosalpinx. The segment
is cut with laparoscopic scissors or alaser,with little risk of bleeding. The mesosalpinx under the pregnancy is coagulated, with
particular attention given to the arcuate anastomosing branches
of the ovarian and uterine vessels.[64] After coagulation, the
mesosalpinx is cut (Figures 9.4.5 and 9.4.6).
Salpingectomy
Guidelines for choosing salpingectomy include the presence of uncontrolled bleeding, tubal destruction by the EUP,
and a recurrent pregnancy in the same tube. Preoperative
counseling should include the desire of the patient for future
childbearing.
This operation is done by progressively coagulating and cutting the mesosalpinx, beginning with the proximal isthmic portion and progressing to the fimbriated end of the tube. It is separated from the uterus by using bipolar coagulation and scissors
or a laser (Figure 9.4.7). A multifire stapling device for salpingectomy requires a 12-mm trocar and is expensive. Alternatively, one or two Endoloops (Ethicon) can be applied around
the salpinx and then cut. The isolated segment containing the
EUP is removed intact or in sectioned parts through the 10-mm
trocar sleeve. Products of conception can be placed in a bag
(Endopouch, Ethicon) and removed (Figure 9.4.8). Adhesions
and other pathologic processes, such as endometriosis, aretreated
during removal of the EUP without prolonging the operation.
Occasionally, a patient is admitted overnight to be observed for
postoperative bleeding and to receive emotional support from
the infertility team.
Salpingectomy or Salpingotomy
There has been considerable debate about whether salpingectomy or salpingostomy should be done at the time of surgery
for an ectopic pregnancy. The possible advantages of removing the tube completely include almost entirely eliminating the
risk of persistent trophoblast and that of a subsequent ectopic
pregnancy, whereas the possible advantage of conserving the
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Bipolar coagulation at
proximal end of ectopic
B
Bipolar coagulation
at distal end of ectopic
C
Figure 9.4.5. (Continued )(B) The bipolar forceps coagulates the proximal isthmic segment. (C) Electrocoagu-
lation of the tube distal to the ectopic pregnancy.
Scissors (or CO2 laser) transect
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the coagulated regions
Management of the Ectopic Pregnancy — 225
A
Figure 9.4.6. (A) Either a scissors or a CO2laser is employed to transect the areas. (Continued)
fallopian tube isthat future fertility is preserved.[40] Thereareno
randomized controlled trials published that specifically compare
laparoscopic or open salpingectomy and salpingotomy. Several
reviewers suggest that subsequent intrauterine pregnancy rates
are similar after both approaches. These data, however, must be
interpreted with caution as the included studies are subject to a
wide range of biases relating to patient selection, surgical procedures used, length of follow-up, and the proportion of patients
lost to follow-up.[65,66]
There are four cohort studies that specifically compare
laparoscopic tube-sparing and radical treatments of ectopic
pregnancy.[67–70] Silva et al. [67] examined reproductive outcomes prospectively in 143 women undergoing laparoscopic
salpingectomy or laparoscopic salpingotomy. The intrauterine
pregnancy rates were similar when comparing the two groups
(intrauterine pregnancy in 60% of subjects after salpingotomy
versus 54% after salpingectomy; relative risk 1.11). In a study of
155 women, Job-Spira et al. [68] reported subsequent intrauterine pregnancy rates with salpingotomy that were comparable to
those following salpingectomy (hazard ratio, 1.22). The cumulative pregnancy rates at 1 year were 72.4% after salpingotomy and
56.3% after salpingectomy.Ina study by Mol et al.[69]of a cohort
of 135 women, the fecundity rate ratio when comparing laparoscopic salpingotomy with salpingectomy during the 18-month
follow-up period was 1.4 for women with a healthy contralateral tube and 3.1 for women with contralateral tubal disease.
The 3-year cumulative pregnancy rate was 62% after salpingotomy and 38% after salpingectomy. In a study by Bangsgaard et
al. [70] reviewing a cohort of 276 women undergoing salpingotomy or salpingectomy, the subsequent cumulative pregnancy
rate at 7 years was 89% following salpingotomy and 66% following salpingectomy. The hazard ratio for intrauterine pregnancy
following salpingectomy was0.63 when compared with salpingotomy. Regardless of thetype ofsurgery, contralateral tubal abnormalities predispose the patient to recurrent ectopic pregnancy.
There was no significant difference in the risk of repeat ectopic
pregnancy (17% after conservative surgery and 16% after radical
surgery).[70]
In summary, in the absence of a randomized study, salpingotomy remains the definitive and universal treatment for EUP
in women who are hemodynamically stable and who wish to
preserve their fertility.[1,2] The reproductive performance after
salpingotomy appears to be equivalent to or better than that
after salpingectomy, but the recurrent EUP rate may be slightly
greater.Salpingectomy may be necessary for women with uncontrolled bleeding, recurrent ectopic pregnancy in the same tube,
a severely damaged tube, or a tubal gestational sac greater than
5 cm in diameter.[1]
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The mesosalpinx is exposed
and electrocoagulated
B
The mesosalpinx
is transected
C
Figure 9.4.6. (Continued )(B) The adjacent mesosalpinx is coagulated. (C) The isthmic ectopic pregnancy is
removed. (Continued )
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