Ectopic Pregnancy
INTRODUCTION
Ectopic pregnancy presents a major
health problem for women of childbearing age. It is the result of a flaw
in human reproductive physiology that allows the conceptus to implant and
mature outside of the endometrial cavity, which ultimately ends in the
demise of the fetus. Without timely diagnosis and treatment, ectopic
pregnancy can become a life-threatening situation.
Ectopic pregnancy currently is the leading cause of pregnancy-related death during the first trimester in the United States, accounting for 9% of all pregnancy-related deaths. In addition to the immediate morbidity caused by ectopic pregnancy, the woman’s future ability to reproduce may be adversely affected as well.
History of the Procedure: Ectopic pregnancy was first described in the 11th century, and, until the middle of the 18th century, it was usually fatal. John Bard reported the first successful surgical intervention to treat an ectopic pregnancy in New York City in 1759.
The survival rate in the early 19th century was dismal. One report demonstrated only 5 patients out of 30 surviving the abdominal operation. Interestingly, the survival rate in patients who were left untreated was 1 of 3.
In the beginning of the 20th century, great improvements in anesthesia, antibiotics, and blood transfusion contributed to the decrease in the maternal mortality rate. In the early half of the 20th century, 200-400 deaths per 10,000 cases were attributed to ectopic pregnancy. In 1970, the Centers for Disease Control and Prevention (CDC) began to record the statistics regarding ectopic pregnancy, reporting 17,800 cases. By 1992, the number of ectopic pregnancies had increased to 108,800. Concurrently, however, the case-fatality rate decreased from 35.5 deaths per 10,000 cases in 1970 to 2.6 per 10,000 cases in 1992.
Problem: Ectopic pregnancy is derived from the Greek word ektopos, meaning out of place, and it refers to the implantation of a fertilized egg in a location outside of the uterine cavity, including the fallopian tubes, cervix, ovary, cornual region of the uterus, and the abdominal cavity. This abnormally implanted gestation grows and draws its blood supply from the site of abnormal implantation. As the gestation enlarges, it creates the potential for organ rupture because only the uterine cavity is designed to expand and accommodate fetal development. Ectopic pregnancy can lead to massive hemorrhage, infertility, or death.
Frequency: Since 1970, the frequency of ectopic pregnancy has increased 6-fold, and it now occurs in 2% of all pregnancies. An estimated 108,800 ectopic pregnancies in 1992 resulted in 58,200 hospitalizations with an estimated cost of $1.1 billion.
Etiology: Multiple factors contribute to the relative risk of ectopic pregnancy. In theory, anything that hampers the migration of the embryo to the endometrial cavity could predispose women to ectopic gestation. The most logical explanation for the increasing frequency of ectopic pregnancy is previous pelvic infection; however, most patients presenting with an ectopic pregnancy have no identifiable risk factor. The following risk factors have been linked with ectopic pregnancy:
Pelvic inflammatory disease
The most common cause is antecedent infection caused by Chlamydia trachomatis. Patients with chlamydial infection have a range of clinical presentations, from asymptomatic cervicitis to salpingitis and florid pelvic inflammatory disease (PID). More than 50% of women who have been infected are unaware of the exposure. Other organisms causing PID, such as Neisseria gonorrhoeae, increase the risk of ectopic pregnancy. A history of salpingitis increases the risk of ectopic pregnancy 4-fold. The incidence of tubal damage increases after successive episodes of PID (ie, 13% after 1 episode, 35% after 2 episodes, 75% after 3 episodes).
History of prior ectopic pregnancy
After one ectopic pregnancy, a patient incurs a 7- to 13-fold increase in the likelihood of another ectopic pregnancy. Overall, a patient with prior ectopic pregnancy has a 50-80% chance of having a subsequent intrauterine gestation, and a 10-25% chance of a future tubal pregnancy.
History of tubal surgery and conception after tubal ligation
Prior tubal surgery has been demonstrated to increase the risk of developing ectopic pregnancy. The increase depends on the degree of damage and the extent of anatomic alteration. Surgeries carrying higher risk of subsequent ectopic pregnancy include salpingostomy, neosalpingostomy, fimbrioplasty, tubal reanastomosis, and lysis of peritubal or periovarian adhesions.
Conception after previous tubal ligation increases a women’s risk of developing ectopic pregnancies. Thirty-five to 50% of patients who conceive after a tubal ligation are reported to experience an ectopic pregnancy. Failure after bipolar tubal cautery is more likely to result in ectopic pregnancy than occlusion using suture, rings, or clips. Failure is attributed to fistula formation that allows sperm passage. Ectopic pregnancies following tubal sterilizations usually occur 2 or more years after sterilization, rather than immediately after. In the first year, only about 6% of sterilization failures result in ectopic pregnancy.
Use of fertility drugs or assisted reproductive technology
Ovulation induction with clomiphene citrate or injectable gonadotropin therapy has been linked with a 4-fold increase in the risk of ectopic pregnancy in a case-control study. This finding suggests that multiple eggs and high hormone levels may be significant factors.
One study has demonstrated that infertility patients with luteal phase defects have a statistically higher ectopic pregnancy rate than patients whose infertility is caused by anovulation. The risk of ectopic pregnancy and heterotopic pregnancy (ie, pregnancies occurring simultaneously in different body sites) dramatically increases when a patient has used assisted reproductive techniques to conceive, such as in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). In a study of 3000 clinical pregnancies achieved through in vitro fertilization, the ectopic pregnancy rate was 4.5%, which is more than double the background incidence. Furthermore, studies have demonstrated that up to 1% of pregnancies achieved through IVF or GIFT can result in a heterotopic gestation, compared to an incidence of 1 in 30,000 pregnancies for spontaneous conceptions.
Use of an intrauterine device
The presence of an inert copper-containing or progesterone intrauterine device (IUD) traditionally has been thought to be a risk factor for ectopic pregnancy. However, only the progesterone IUD has a rate of ectopic pregnancy higher than that for women not using any form of contraception. The modern copper IUD does not increase the risk of ectopic pregnancy. Nevertheless, if a woman ultimately conceives with an IUD in place, it is more likely to be an ectopic pregnancy. The actual incidence of ectopic pregnancies with IUD use is 3-4%.
Increasing age
The highest rate of ectopic pregnancy occurs in women aged 35-44 years. A 3- to 4-fold increase in the risk for developing an ectopic pregnancy exists compared to women aged 15-24 years. One proposed explanation involves the myoelectrical activity in the fallopian tube, which is responsible for tubal motility. Aging may result in a progressive loss of myoelectrical activity along the fallopian tube.
Smoking
Cigarette smoking has been shown to be a risk factor for developing an ectopic pregnancy. Studies have demonstrated elevated risk ranging from 1.6-3.5 times that of nonsmokers. A dose-response effect also has been suggested. On the basis of laboratory studies in humans and animals, researchers have postulated several mechanisms by which cigarette smoking might play a role in ectopic pregnancies. These mechanisms include one or more of the following: delayed ovulation, altered tubal and uterine motility, or altered immunity. To date, no study has supported a specific mechanism by which cigarette smoking affects the occurrence of ectopic pregnancy.
Salpingitis isthmica nodosum
Salpingitis isthmica nodosum is defined as the microscopic presence of tubal epithelium in the myosalpinx or beneath the tubal serosa. These pockets of epithelium protrude through the tube, similar to small diverticula. Studies of serial histopathological sections of the fallopian tube have revealed that approximately 50% of patients treated with salpingectomy for ectopic pregnancy have evidence of salpingitis isthmica nodosum. The etiology of salpingitis isthmica nodosum is unclear, but proposed mechanisms include postinflammatory and congenital as well as acquired tubal changes such as observed with endometriosis.
Other
Other risk factors associated with increased incidence of ectopic pregnancy include previous diethylstilbestrol (DES) exposure, a T-shaped uterus, prior abdominal surgery, failure with progestin-only contraception, and ruptured appendix.
Pathophysiology: Most ectopic pregnancies are located in the fallopian tube (see Image 1). The most common site is the ampullary portion of the tube, where over 80% occur. The next most common sites are the isthmic segment of the tube (12%), the fimbria (5%), and the cornual and interstitial region of the tube (2%). Nontubal sites of ectopic pregnancy are a rare occurrence, with abdominal pregnancies accounting for 1.4% of ectopic pregnancies and ovarian and cervical sites accounting for 0.2% each.
Clinical: The classic clinical triad of ectopic pregnancy is pain, amenorrhea, and vaginal bleeding. Unfortunately, only 50% of patients present typically. Patients may present with other symptoms common to early pregnancy, including nausea, breast fullness, fatigue, low abdominal pain, heavy cramping, shoulder pain, and recent dyspareunia. Astute clinicians should have a high index of suspicion for ectopic pregnancy in any woman who presents with these symptoms and who presents with physical findings of pelvic tenderness, enlarged uterus, adnexal mass, or tenderness.
Remember, however, that only 40-50% of patients with an ectopic pregnancy present with vaginal bleeding, 50% have a palpable adnexal mass, and 75% may have abdominal tenderness. Approximately 20% of patients with ectopic pregnancies are hemodynamically compromised at initial presentation, which is highly suggestive of rupture. Fortunately, using modern diagnostic techniques, most ectopic pregnancies may be diagnosed prior to rupturing.
Numerous conditions may have a presentation similar to an extrauterine pregnancy. The most common of these are appendicitis, salpingitis, ruptured corpus luteum cyst or ovarian follicle, spontaneous abortion or threatened abortion, ovarian torsion, and urinary tract disease. Intrauterine pregnancies with other abdominal or pelvic problems such as degenerating fibroids must also be included in the differential diagnosis.
INDICATIONSMedical therapy
Medical therapy involving methotrexate may be indicated in certain patients. A number of factors must be considered. The patient must be hemodynamically stable, with no signs or symptoms of active bleeding or hemoperitoneum. Furthermore, she must be reliable, compliant, and able to return for follow-up. Another factor is size of the gestation, which should not exceed 3.5 cm at its greatest dimension on ultrasound (US) measurement. She should not have any contraindications to the use of methotrexate.
Surgical therapy
Within the last 2 decades, a more conservative surgical approach to unruptured ectopic pregnancy using minimally invasive surgery has been advocated to preserve tubal function (see Surgical therapy). Laparoscopy has become the recommended approach in most cases. Laparotomy is usually reserved for patients who are hemodynamically unstable or patients with cornual ectopic pregnancies. It also is a preferred method for surgeons inexperienced in laparoscopy and in patients where laparoscopic approach is difficult (eg, secondary to the presence of multiple dense adhesions, obesity or massive hemoperitoneum). In a patient who has completed childbearing and no longer desires fertility, in a patient with a history of an ectopic pregnancy in the same tube, or in a patient with severely damaged tubes, total salpingectomy is the procedure of choice.
Expectant management
Candidates for successful expectant management are asymptomatic and have no evidence of rupture or hemodynamic instability. Furthermore, they should portray objective evidence of resolution, such as declining bhCG levels. They must be fully compliant and must be willing to accept the potential risks of tubal rupture.
RELEVANT ANATOMY AND
CONTRAINDICATIONS
Contraindications: A bhCG level of greater than 15,000 IU/L, fetal cardiac activity, and
free fluid in the cul-de-sac on US (presumably representing tubal rupture)
are contraindications to medical therapy with methotrexate. Other
contraindications to the use of methotrexate include documented
hypersensitivity to methotrexate; breastfeeding; immunodeficiency;
alcoholism; alcoholic liver disease or any liver disease; blood
dyscrasias; leukopenia; thrombocytopenia; anemia; active pulmonary
disease; peptic ulcer disease; and renal, hepatic, or hematologic
dysfunction.
Surgical therapy
Surgical treatment in cases in which the pregnancy is located on the
cervix, ovary, or in the interstitial or the cornual portion of the tube
is often associated with increased risk of hemorrhage, often resulting in
hysterectomy or oophorectomy. In these cases, treatment with methotrexate
is an especially attractive option.
In cases involving uncontrolled bleeding and hemodynamic instability,
conservative treatment methods are avoided in favor of radical surgery.
Lab Studies: Imaging Studies:
Diagnostic Procedures: Methotrexate is an antimetabolite chemotherapeutic agent that binds to
the enzyme dihydrofolate reductase, which is involved in the synthesis of
purine nucleotides. This interferes with DNA synthesis and disrupts cell
multiplication. Methotrexate has long been known to be effective in the
treatment of leukemias, lymphomas, and carcinomas of the head, neck,
breast, ovary, and bladder. It has also been used as an immunosuppressive
agent in the prevention of graft versus host disease and in the treatment
of severe psoriasis and rheumatoid arthritis. Its effectiveness on
trophoblastic tissue has been well established and is derived from
experience gained in using methotrexate in the treatment of hydatiform
moles and choriocarcinomas. Methotrexate is used in the treatment of
ectopic pregnancy as single or multiple intramuscular injections.
Adverse effects associated with the use of methotrexate can be divided
into drug adverse effects and treatment effects. Drug adverse effects
include nausea, vomiting, stomatitis, diarrhea, gastric distress, and
dizziness. Transient elevation in liver enzymes is also known to occur.
Serious reactions, such as bone marrow suppression, dermatitis, pleuritis,
pneumonitis, and alopecia, can occur with higher doses and are rare with
doses used in the treatment of ectopic pregnancy. Treatment effects of
methotrexate include an increase in abdominal pain (occurring in up to two
thirds of patients), an increase in bhCG levels during first 1-3 days of
treatment, and vaginal bleeding or spotting.
In determining whether a patient is a candidate for medical therapy, a
number of factors must be considered. She must be hemodynamically stable,
with no signs or symptoms of active bleeding or hemoperitoneum.
Furthermore, she must be reliable, compliant, and able to return for
follow-up. Another factor is size of the gestation, which should not
exceed 3.5 cm at its greatest dimension on US measurement. She should not
have any contraindications to the use of methotrexate.
A bhCG level of greater than 15,000 IU/L, fetal cardiac activity, and
free fluid in the cul-de-sac on US (presumably representing tubal rupture)
are contraindications. Although patients with bhCG levels above 15,000
IU/L and fetal cardiac activity have been treated successfully with
methotrexate these patients require much greater surveillance and carry a
higher risk of subsequent operative intervention. Contraindications to the
use of methotrexate include documented hypersensitivity to methotrexate;
breastfeeding; immunodeficiency; alcoholism; alcoholic liver disease or
any liver disease; blood dyscrasias; leukopenia; thrombocytopenia; anemia;
active pulmonary disease; peptic ulcer disease; and renal, hepatic, or
hematologic dysfunction. However, in each case, the risk of surgery must
be weighed against any relative contraindication.
A number of accepted protocols with injected methotrexate exist for the
treatment of ectopic pregnancy. Initial experience used multiple doses of
methotrexate with leucovorin to minimize adverse effects. Leucovorin is
folinic acid that is the end product of the reaction catalyzed by
dihydrofolate reductase, the same enzyme inhibited by methotrexate. Normal
dividing cells preferentially absorb leucovorin; hence, it decreases the
action of methotrexate, thereby decreasing its systemic adverse effects.
This regimen involves administration of methotrexate as 1 mg/kg IM on days
0, 2, 4, and 6, followed by 4 doses of leucovorin as 0.1 mg/kg on days 1,
3, 5, and 7. Because of higher incidence of adverse effects and the
increased need for patient motivation and compliance, the multiple dose
regimen has fallen out of favor in the United States.
The more popular regimen today is the single dose injection. It
involves injection of methotrexate as 50 mg/m2 IM in a single
injection or as a divided dose injected into each buttock. With smaller
dosing and fewer injections, fewer adverse effects are anticipated and the
use of leucovorin can be abandoned.
Prior to injection of methotrexate, the patient must be counseled
extensively on the risks, benefits, adverse effects, and the possibility
of failure of medical therapy, which would result in tubal rupture
necessitating surgery. Patients should be aware of the signs and symptoms
associated with tubal rupture and be advised to contact their physician
with significantly worsening abdominal pain or tenderness, heavy vaginal
bleeding, dizziness, tachycardia, palpitations, or syncope.
Most patients experience at least one episode of increased abdominal
pain, which usually occurs 2-3 days after the injection. Increased
abdominal pain is believed to be caused by the separation of the pregnancy
from the implanted site. It can be differentiated from tubal rupture in
that it is milder, of limited duration (lasting 24-48 h), and is not
associated with signs of acute abdomen or hemodynamic instability.
Advise patients to avoid alcoholic beverages, vitamins containing folic
acid, nonsteroidal anti-inflammatory drugs, and sexual intercourse until
advised otherwise. A signed written consent demonstrating the patient’s
comprehension of the course of treatment must be obtained. Provide an
information pamphlet to all patients receiving methotrexate; the pamphlet
should include a list of adverse effects, a schedule of follow-up visits,
and a method of contacting the physician or the hospital in case of
emergency.
Before initiating therapy, draw blood to determine baseline laboratory
values for renal, hepatic, and bone marrow function, as well as a baseline
bhCG level. Determine blood type, Rhesus (Rh) factor, and the presence of
antibodies. Patients who are Rh negative should receive Rh immune
globulin. Obtain repeat bhCG levels 4 days and 7 days after the
methotrexate injection. An initial increase in bhCG levels often occurs by
the third day and is not a cause for alarm. A decline in bhCG levels of at
least 15% from days 4-7 postinjection indicates a successful medical
response. Monitor the patient’s bhCG levels weekly until they become
undetectable.
Failure of medical treatment is defined when bhCG levels increase,
plateau, or fail to decrease adequately by 15% from days 4-7
postinjection. At this time, surgical intervention may be warranted. A
repeat single dose of methotrexate can also be a viable option after
reevaluation of the patients' indications and contraindications (including
repeat US) for medical therapy.
Treatment with methotrexate is an especially attractive option when the
pregnancy is located on the cervix, ovary, or in the interstitial or the
cornual portion of the tube. Surgical treatment in these cases is often
associated with increased risk of hemorrhage, often resulting in
hysterectomy or oophorectomy (see Images 3-4).
Successful medical treatment using methotrexate has been reported in the
literature with good subsequent reproductive outcomes. By avoiding
surgery, the risk of tubal injury is reduced.
The use of oral methotrexate currently is under investigation, and,
while preliminary reports show promising results, efficacy remains to be
established. Direct local injection (salpingocentesis) of methotrexate
into the ectopic pregnancy under laparoscopic or US guidance has also been
reported in the literature; however, reports from these studies have
yielded inconsistent results, and its advantage over intramuscular
injection remains to be established.
The medical treatment of ectopic pregnancy requires compulsive
compliance. The physician must emphasize the importance of patient
follow-up and have patient information on hand, including the patient's
home address, telephone numbers at home and work, and the means to reach a
contact person in case attempts to reach the patient directly are
unsuccessful. Proper documentation of attempts to reach the patient,
including records of telephone calls and certified mail are important
medical-legal considerations.
Surgical therapy: With advances in
the ability to make earlier diagnosis and improvements in microsurgical
techniques, conservative surgery has replaced the standard laparotomy with
salpingectomy of the past. Within the last 2 decades, a more conservative
surgical approach to unruptured ectopic pregnancy using minimally invasive
surgery has been advocated to preserve tubal function. The conservative
approaches include linear salpingostomy and milking the pregnancy out of
the distal ampulla. The more radical approach includes resecting the
segment of the fallopian tube that contains the gestation with or without
reanastomosis.
Laparoscopy has become the recommended approach in most cases.
Laparotomy is usually reserved for patients who are hemodynamically
unstable or patients with cornual ectopic pregnancies. It also is a
preferred method for surgeons inexperienced in laparoscopy and in patients
where laparoscopic approach is difficult (eg, secondary to the presence of
multiple dense adhesions, obesity or massive hemoperitoneum). Multiple
studies have demonstrated that laparoscopic treatment of ectopic pregnancy
results in fewer postoperative adhesions than laparotomy. Furthermore,
laparoscopy is associated with significantly less blood loss and a reduced
need for analgesia. Finally, laparoscopy reduces cost, hospitalization,
and convalescence period.
Linear salpingostomy along the antimesenteric border to remove the
products of conception is the procedure of choice for unruptured ectopic
pregnancies in the ampullary portion of the tube. Ectopic pregnancies in
the ampulla are usually located between the lumen and the serosa and,
thus, are ideal candidates for linear salpingostomy. Several studies have
demonstrated no benefit of primary closure (salpingotomy) over healing by
secondary intention (salpingostomy).
The involved tube is identified and freed from surrounding structures.
To minimize bleeding, a dilute solution containing 20 U of vasopressin in
20 mL of isotonic sodium chloride solution may be injected into the
mesosalpinx just below the ectopic pregnancy. Make sure that the needle is
not in a blood vessel by aspirating before injecting because intravascular
injection of vasopressin may precipitate acute arterial hypertension and
bradycardia.
Next, using a microelectrode, scissors, harmonic scalpel, or laser, a
1- to 2-cm linear incision is made along the antimesenteric side of the
tube along the thinnest segment of the gestation (see Some ampullary pregnancies can be teased out and expressed through the
fimbrial end (milking of the tube) by using digital expression, suction,
or aqua-dissection. However, this approach carries with it a higher rate
of bleeding, persistent trophoblastic tissue, tubal damage, and recurrent
ectopic pregnancy (33%).
In some cases, resection of the tubal segment containing the gestation
or a total salpingectomy is preferred over salpingostomy. This is true for
isthmic pregnancies, where the endosalpinx is usually damaged. These
patients do poorly with linear salpingostomy, with a high rate of
recurrent ectopic pregnancy. Segmental tubal resection is performed by
grasping the tube at the proximal and distal borders of the segment of the
tube containing the gestation and coagulating thoroughly from the
antimesenteric border to the mesosalpinx. This portion of the tube is then
excised. The underlying mesosalpinx is also coagulated and excised, with
particular attention to minimize the damage to the surrounding
vasculature. Delayed microsurgical reanastomosis can be performed to
reestablish tubal patency if enough healthy fallopian tube is present.
Take care to minimize the thermal injury to the tube during excision, so
that an adequate portion of healthy tube remains for the reanastomosis.
Total salpingectomy can be achieved by progressively coagulating and
cutting the mesosalpinx, starting from the fimbriated end and advancing
toward the proximal isthmic portion of the tube. At this point, the tube
is separated from the uterus by coagulating and excising with scissors or
laser.
Preoperative details: The optimal surgical management
for a patient with an ectopic pregnancy depends on several factors,
including the following:
In a patient who has completed childbearing and no longer desires
fertility, in a patient with a history of an ectopic pregnancy in the same
tube, or in a patient with severely damaged tubes, total salpingectomy is
the procedure of choice. The presence of uncontrolled bleeding and
hemodynamic instability warrants radical surgery over conservative
methods. The preferred approach based on the location of the pregnancy
varies, as discussed above. In all instances, regardless of desired
fertility, fully inform the patient of the possibility of a laparotomy
with bilateral salpingectomy.
Intraoperative details: Throughout the procedure, take
care to minimize blood loss and reduce the potential for retained
trophoblastic tissue, which can reimplant and persist. Remove large
gestations in an endoscopic bag, and perform copious irrigation and
suctioning to remove any remaining fragments. Inspect the peritoneal
cavity and remove any detected residual trophoblastic tissue.
Note the condition of the contralateral tube, the presence of
adhesions, or other pathologic processes because this helps in the
postoperative counseling of the patient with regard to future fertility
potential.
Postoperative details: Proper pain control and
hemodynamic stability are important postoperative considerations. Most
often, patients treated with laparoscopy are discharged on the same day of
surgery; however, overnight admission may be necessary for some patients
to monitor postoperative bleeding and achieve adequate pain control.
Patients treated by laparotomy are usually hospitalized for a few days.
Follow-up care: After surgical excision of the ectopic
gestation, weekly monitoring of quantitative bhCG levels is necessary
until the level is zero to ensure that treatment is complete. This is
especially true following treatment with conservative surgery, ie,
salpingostomy, which carries a 5-15% rate of persistent trophoblastic
tissue. The average time for bhCG to clear the system is 2-3 weeks, but up
to 6 weeks can be required.
After tubal-sparing surgical removal of an ectopic pregnancy, a fall in
bhCG levels of less than 20% every 72 hours represents incomplete
treatment. Although most of these cases are caused by incomplete removal
of trophoblastic tissue, some actually may represent multiple ectopic
pregnancies in which only one gestation is initially recognized and
treated.
The incidence of persistent trophoblastic tissue is greater with higher
initial bhCG levels and is relatively rare with titers less than 3000
IU/L. The risk of persistent trophoblastic tissue is very significant with
a hematosalpinx greater than 6 cm in diameter, a bhCG titer greater than
20,000 IU/L, and a hemoperitoneum greater than 2 L. While resolution
without any further intervention is the general rule, the persistence of
trophoblastic tissue has been associated with tubal rupture and hemorrhage
even in the presence of declining bhCG levels. Further medical treatment
with methotrexate or surgery in symptomatic patients may be necessary if
bhCG levels do not decline or persist.
Expectant management
The increased incidence of ectopic pregnancy is partially attributed to
improved ability in making earlier diagnosis. Ectopic pregnancies that
previously would have resulted in tubal abortion or complete spontaneous
reabsorption and remained clinically undiagnosed are now detected. Some
investigators have questioned the need for unnecessary surgical or medical
intervention in very early cases and have advocated expectant management
in select cases. Distinguishing patients who are experiencing spontaneous
resolution of their ectopic pregnancies from patients who have
proliferative ectopic pregnancies could pose a clinical dilemma.
Candidates for successful expectant management are asymptomatic and
have no evidence of rupture or hemodynamic instability. Furthermore, they
should portray objective evidence of resolution, such as declining bhCG
levels. They must be fully compliant and must be willing to accept the
potential risks of tubal rupture.
Approximately one fourth of women presenting with ectopic pregnancies
have declining bhCG levels, and 70% of this group experience successful
outcomes with close observation, as long as the gestation is 4 cm or less
in greatest dimension. An initial low bhCG titer also correlates with
successful spontaneous resolution. While data are limited on this matter,
initial bhCG titers below 1000 mIU/mL have been demonstrated to predict
successful outcome in 88% of cases managed expectantly.
Remember that no cutoff value below which expectant management is
uniformly safe has been established. Furthermore, rupture despite low and
declining serum levels of bhCG has been reported, making close follow-up
and patient compliance of paramount importance.
Any time a surgical approach is chosen as the treatment of choice,
consider the complications attributable to the surgery, whether it is
laparotomy or laparoscopy. These include bleeding, infection, and damage
to surrounding organs, such as bowel, bladder, ureters, and the major
vessels nearby. Consider risks and complications secondary to anesthesia.
Make the patient aware of these complications and obtain the appropriate
written consents.
The evidence in the literature reporting on the treatment of ectopic
pregnancy with subsequent reproductive outcome is limited mostly to
observational data and a few randomized trials comparing the various
treatment options. Assessment of successful treatment and future
reproductive outcome with various treatment options is often skewed by
selection bias. For example, comparing a patient who was managed
expectantly to a patient who received methotrexate or to a patient who had
a laparoscopic salpingectomy is difficult. A patient with spotting, no
abdominal pain, and a low initial bhCG level that is falling may be
managed expectantly, while a patient who presents with hemodynamic
instability, an acute abdomen, and high initial bhCG levels must be
managed surgically. These two patients probably represent different
degrees of tubal damage, and comparing the future reproductive outcomes of
the two would be flawed.
Data in the literature have failed to demonstrate substantial and
consistent benefit of either salpingostomy or salpingectomy in improving
future reproductive outcome. Despite the risk of persistent ectopic
pregnancy, some studies have shown salpingostomy to improve reproductive
outcome in patients with contralateral tubal damage.
In 1997, Yao and Tulandi concluded from a literature review that
laparoscopic salpingostomy had equal or slightly better reproductive
performance than salpingectomy; however, slightly higher recurrent ectopic
pregnancy rates were noted in the salpingostomy group.
Dubuisson et al (1996), reporting on 10 years of surgical experience in
Paris, concluded that, for selected patients who desired future fertility,
using salpingectomy, which is simpler and avoids the risk of persistent
ectopic pregnancy, is possible and can result in a comparable fertility
rate to tubal conservation surgery. Future fertility rates were no
different with either surgical approach when the contralateral tube was
either normal or scarred but patent. In 1996, Clausen reported on a review
of the past 40 years and concluded that only a small number of
investigators have suggested indirectly that conservative tubal surgery
increases the rate of subsequent intrauterine pregnancy, and the more
recent studies may reflect an improvement in surgical technique. Maymon et
al (1995), after reviewing 20 years of ectopic pregnancy treatment,
concluded that conservative tubal surgery provided no greater risk of
recurrent ectopic pregnancy than the more radical salpingectomy.
Parker and Bistis (1997) concluded that when the contralateral
fallopian tube is normal, the subsequent fertility rate is independent of
the type of surgery. A prospective study of 88 patients by Ory et al
(1993) indicated that the surgical method had no effect on subsequent
fertility in women with an intact contralateral tube. Prior history of
infertility was the most significant factor affecting postsurgical
fertility. Several other studies have reported that the status of the
contralateral tube, the presence of adhesions, and the presence of other
risk factors such as endometriosis have a more significant impact on
future fertility than choice of surgical procedure. According to Rulin
(1995), salpingectomy should be the treatment of choice in women with
intact contralateral tubes because conservative treatment provides no
additional benefit and incurs the additional costs and morbidity
associated with persistent ectopic pregnancy and recurrent ectopic
pregnancy in the already damaged tube.
Future fertility rates are similar in patients who were treated
surgically by laparoscopy or laparotomy. Salpingectomy by laparotomy
carries a subsequent intrauterine pregnancy rate of 25-70%, compared to
laparoscopic salpingectomy with rates of 50-60%. Very similar rates exist
for laparoscopic salpingostomy versus laparotomy. The rate of persistent
ectopic pregnancy between the two groups is similar, ranging from 5-20%. A
slightly higher recurrent ectopic pregnancy rate exists in patients
treated by laparotomy (7-28%), regardless of conservative or radical
approach, when compared to laparoscopy (6-16%). This surprising finding is
believed to be secondary to increased adhesion formation in the group
treated by laparotomy.
The modern pelvic surgeon has been led to believe that the treatment of
choice for unruptured ectopic pregnancy is salpingostomy, sparing the
affected fallopian tube and thereby improving future reproductive outcome.
However, if the treating surgeon has neither the laparoscopic skill nor
the instrumentation necessary to atraumatically remove the trophoblastic
tissue via linear salpingostomy, then salpingectomy by laparoscopy or
laparotomy is not the wrong choice for operation. Leaving a scarred
charred fallopian tube behind after removing the ectopic pregnancy but
requiring extensive cautery to control bleeding does not preserve
reproductive outcome.
The success rates after methotrexate are comparable with laparoscopic
salpingostomy, assuming the selection criteria mentioned above are
observed. The average success rates using the multiple-dose regimen are in
the range of 91-95%, demonstrated by multiple investigators. One study of
77 patients desiring subsequent pregnancy showed intrauterine pregnancies
in 64%, and recurrent ectopic pregnancy occurred in 11%. Other studies
have demonstrated similar results, with intrauterine pregnancy rates
ranging from 20-80%.
The average success rates for the single-dose regimen are reported to
be from 88-94%. In a study by Stovall and Ling (1992), 113 patients (94%)
were treated successfully, 4 (3.3%) of whom needed a second dose. No
adverse effects were encountered. Furthermore, 87.2% of these patients
achieved a subsequent intrauterine pregnancy, whereas 12.8% experienced a
subsequent ectopic pregnancy. Other studies have reported similar results
with some mild adverse effects and lower reproductive outcomes.
As the ability to diagnose
ectopic pregnancy improves, physicians will be able to intervene sooner,
preventing life-threatening sequelae and extensive tubal damage, which
could preserve future fertility. Already, with improving technology,
physicians are treating ectopic pregnancies with minimally invasive
surgery or no surgery at all. Physicians have been able to reduce the
mortality rate secondary to ectopic pregnancy despite its growing
incidence. Also, effective vaccination against Chlamydia
trachomatis is under investigation. Once clinically available, it
should have a dramatic impact on the frequency of ectopic pregnancy, as
well as on the overall health of the female reproductive system.
IMAGES Caption: Picture 2. Ectopic pregnancy. Laparoscopic picture of an
unruptured right ampullary tubal pregnancy with bleeding out of the
fimbriated end resulting in hemoperitoneum. Caption: Picture 5. Ectopic pregnancy. Linear incision being made at the
antimesenteric side of the ampullary portion of the fallopian tube.
By Donna M. Peretin, RN. Caption: Picture 6. Laparoscopic picture of an ampullary ectopic pregnancy
protruding out after a linear salpingostomy was performed.
Caption: Picture 7. Ectopic pregnancy. Schematic of a tubal gestation being
teased out after linear salpingostomy. By Donna M. Peretin,
RN. REFERENCES:
MEDCEU
Continuing Education Courses CEU for Nurses and Healthcare Professional
Relevant
Anatomy: See Pathophysiology.
Medical therapy
WORKUP
TREATMENT
Medical therapy:
Historically, the treatment of ectopic pregnancy was limited to
surgery. With evolving experience with methotrexate, the treatment of
selected ectopic pregnancies has been revolutionized. Medical therapy of
ectopic pregnancy is appealing over surgical options for a number of
reasons, including eliminating morbidity from surgery and general
anesthesia, potentially less tubal damage, and less cost and need for
hospitalization.
Complications of ectopic pregnancy can
be secondary to misdiagnosis, late diagnosis, or treatment approach.
Failure to make the prompt and correct diagnosis of ectopic pregnancy
could result in tubal or uterine rupture, depending on the location of the
pregnancy, which could lead to massive hemorrhage, shock, disseminated
intravascular coagulopathy (DIC), and death. Ectopic pregnancy is the
leading cause of maternal death in the first trimester, accounting for
9-13% of all pregnancy-related deaths. In the United States, an estimated
30-40 women die each year form ectopic pregnancy.
Treatment success rates and
future reproductive outcome
