Surgical Management of Ectopic Pregnancy

Surgical Management of Ectopic Pregnancy

INTRODUCTION

In the not-so-distant past (30 years ago), ectopic pregnancy was a difficult diagnosis to make and a very common cause of maternal mortality. Because of the development of a rapid test for the beta subunit of human chorionic gonadotropin (hCG) and the development of high-quality ultrasound, ectopic pregnancy is frequently diagnosed early and treated before it can cause morbidity or mortality.

The advent of these two tests is the major reason that maternal morbidity is now measured per 100,000 live births instead of per 10,000 live births, as it was 35 years ago. The advent of laparoscopic surgery further reduced morbidity. Currently, with medical therapy of ectopic pregnancy a reality, many patients never even get admitted to the hospital.

History of the Procedure: Prior to 1883, no woman was ever deliberately and successfully operated on for a ruptured ectopic pregnancy. Robert Lawson Tait, sometimes known as "the father of gynecologic surgery," was born in Edinburgh on May 1, 1845. He was one of many European surgeons to perform an ovariotomy after McDowell performed his history-making Christmas day procedure of 1809. He then started to operate on smaller less diseased ovaries. Tait then progressed to removing fallopian tubes. He apparently never considered the operation for ectopic pregnancy.

In 1881, he was called in consultation to see a patient who had been diagnosed with intraperitoneal hemorrhage secondary to a ruptured tubal pregnancy. The patient's physician suggested that Tait open the abdomen and remove the ruptured tube. Tait rejected the idea. After the woman died, Tait, at postmortem, injected the specimen and determined that if he had operated and tied the broad ligament, he would have arrested the hemorrhage and probably would have saved the woman's life. In April of 1883, he operated on another woman and ligated the ruptured tube and broad ligament. This was the first successful surgical management of ruptured tubal pregnancy. In 1885, Tait analyzed his first 1000 cases of abdominal "section." These included 20 successful operations for ectopic pregnancy.

Following Tait's accomplishment, little occurred in the management of ectopic pregnancy until the 1940s, when blood banking came into use. While this was a major development, the serious difficulty of diagnosis remained in the treatment of ectopic pregnancy. Many women with a little abnormal bleeding and abdominal pain were suspected of having an ectopic, but only a few did. One of the major tools for diagnosis was culdocentesis. This was of no benefit if it was negative and was only positive if the ectopic already was ruptured.

Pregnancy tests in the 1960s did not turn positive until about 6 menstrual weeks. Approximately 50% of all proven ectopic pregnancy had a negative pregnancy test. Starting in the late 1960s, ultrasound was developed along with a sensitive accurate test for the beta subunit of hCG. This technology revolutionized the diagnosis of ectopic pregnancy. At approximately the same time, laparoscopy was developed. This led to the minimally invasive treatment of ectopic pregnancies. Then, in the 1980s, medical treatment of ectopic pregnancy with methotrexate was developed.

Problem: An ectopic pregnancy occurs outside of the uterus. Approximately 97.7% of all ectopics occur in the fallopian tubes, with the rest occurring in the ovary, abdomen, or cervix.

Of tubal pregnancies, the ampulla is the most common site of implantation (80%), followed by the isthmus (11%), fimbria (4%), cornua (2%), and interstitial (3%).

Frequency: The incidence of ectopic pregnancy most commonly is reported as the number of ectopic pregnancies per 1000 conceptions. The incidence varies among populations. Over the last 40 years, the incidence has been increasing steadily.

In 1970, the reported rate in the US was 4.5 per 1000 pregnancies. By 1987, this was reported as 16.8 per 1000 pregnancies. This data is based on Center for Disease Control data that use hospitalizations for ectopic pregnancy to determine the total number of ectopic pregnancies. Looking at raw data, there were 17,800 hospitalizations for ectopics in 1970. This number rose to 88,000 in 1989 but has fallen to 30,000 in 1998. This raises the question of whether the number of ectopics is declining or that many ectopics are now treated in ambulatory surgical centers and even by medical therapy without being admitted. The author and many others believe the latter is true, but real statistics are lacking. The incidence is estimated at 1 in 40 pregnancies or about 25 per 1000 pregnancies.

About 85-90% of ectopics occur in multigravid women. In the US, rates are nearly twice as high for nonwhite as for white women.

Etiology: The main cause of ectopic pregnancy is salpingitis. The morphologic sequelae of acute salpingitis can be seen in approximately 50% of ectopic pregnancies. No pathologic changes can be found in about 40%. This leads to the assumption that in these situations, a physiologic disorder results in the ectopic pregnancy. Passage of the zygote through the tube may be delayed until it implants in the tube. Another cause is failed tubal surgical sterilization. Of all pregnancies occurring in women who have undergone a tubal ligation, 30-35% are ectopic pregnancies. In nearly half of ectopic pregnancies, no anatomic lesion can be found. This may be the result of a "physiologic" etiology, including things that slow tubal motility, most probably progestational agents. Progestin-containing intrauterine devices may lead to a local excess of progestin activity that could slow tubal motility.

Pathophysiology: Delay or prevention of passage of the fertilized ovum (blastocyst) to the uterine cavity by the factors as above or factors inherent in the embryo that result in premature implantation.

Clinical: The most common clinical presentation is pelvic pain and/or vaginal spotting. This usually occurs 4-8 weeks after the last menstrual period. Abdominal tenderness may be seen on examination. On pelvic exam, usually tenderness is seen. If a mass is palpable, it is most likely a corpus luteum on the ovary. The ectopic usually is too small, tender, and soft to be palpable.

Pain usually is the result of stretching of the peritoneum over the tube. Once the tube ruptures, pain usually decreases or disappears.

If the tube has ruptured, the patient may present in shock with tachycardia and hypotension. Shoulder pain from diaphragmatic irritation is a late sign and seldom is seen today.

WORKUP

Lab Studies:

Human chorionic gonadotropin (hCG) (quantitative)

The quantitative level of beta hCG found in ectopic pregnancy varies. Serum-beta hCG levels correlate with the size and gestational age in normal embryonic growth. In a normal pregnancy, the beta hCG level doubles every 48 hours until it reaches 10,000-20,000 mIU/mL. With ectopics, beta hCG levels usually have less of an increase.

The discriminatory zone of beta hCG is the level above which a normal intrauterine pregnancy (IUP) is reliably visualized. Once beta hCG has reached a level of 2000 mIU/mL, a gestational sac should be seen within the uterus on a transvaginal ultrasound scan. Once it has reached 6000 mIU/mL, a gestational sac should be visualized within the uterus by an abdominal scan.

The lack of an IUP when the beta is above the discriminatory zone represents an ectopic pregnancy or a recent abortion.

Perform serial hemoglobin or hematocrit levels to quantify blood loss.

Imaging Studies:

Endovaginal ultrasonography can be performed in the outpatient clinic or emergency room to exclude an IUP.

Definite IUP: A gestational sac with a sonolucent center (greater than 5-mm diameter) is surrounded by a thick, concentric, echogenic ring located within the endometrium and contains a fetal pole, yolk sac, or both.

Probable abnormal IUP: A gestational sac larger than 10-mm diameter without a fetal pole or the presence of a definite fetal pole without cardiac activity. This frequently has an irregular or crenelated border.

Definite ectopic pregnancy: The presence of a thick, brightly echogenic, ringlike structure located outside the uterus with a gestational sac containing an obvious fetal pole, yolk sac, or both. This is an unusual finding.

No definite IUP (empty uterus): An empty uterus on endovaginal ultrasound in patients with a serum beta hCG greater than the discriminatory cut-off value is an ectopic pregnancy until proven otherwise. An empty uterus also may represent a recent abortion.

Other ultrasonographic findings include an adnexal mass(usually a corpus luteum, occasionally hematoma), free cul-de-sac fluid, and/or severe adnexal tenderness with probe palpation. Patients with no definite IUP and the above-mentioned findings may be at high risk for an ectopic pregnancy.

An appreciation for the sonographic spectrum of ultrasound findings in ectopic pregnancy may allow physicians to recognize an early ectopic pregnancy. The spectrum of sonographic findings in ectopic pregnancy include the following:

Tubal ring: An echogenic ringlike structure found outside of the uterus represents an early ectopic pregnancy.

Extrauterine mass: The presence of a tender adnexal mass on ultrasound suggests an ectopic pregnancy. One study suggested that the presence of any adnexal mass other than a simple cyst was the most significant ultrasound finding for the diagnosis of ectopic pregnancy.

Interstitial ectopic: An interstitial ectopic pregnancy is one that implants at the highly vascular region of the uterus near the insertion of the fallopian tube. These types can grow larger than those within the fallopian tube, because the endometrial tissue is more expandable. Because of the increased size and partial endometrial implantation, these advanced ectopics can be misdiagnosed as an IUP. An aid in the diagnosis of an interstitial ectopic is the eccentric location of the gestational sac. It is important to evaluate the amount of uterine myometrium surrounding the gestational sac and echogenic decidual layer. This is termed the myometrial mantle. At least 5 mm of myometrium should be present. If there is more than 5 mm, this suggests the diagnosis. Another sonographic finding is the interstitial line sign.

Heterotopic pregnancy: This is a combined IUP and ectopic pregnancy. It may occur in approximately 1:30,000 pregnancies and more commonly in patients taking fertility agents.

Extrauterine empty gestational sac: The presence of an extrauterine mass with a thick, brightly echogenic band (ring) also may represent an ectopic.

Hemosalpinx: Fallopian tubes may fill with blood or free fluid.

Ruptured ectopic: Findings on ultrasound include free fluid or clotted blood in the cul-de-sac or in the intraperitoneal gutters, such as Morison pouch.

Diagnostic Procedures:

Culdocentesis can be performed to diagnose blood in the cul-de-sac. Ultrasound is relatively noninvasive and is more sensitive for cul-de-sac fluid but cannot distinguish between peritoneal fluid and blood.

Menstrual aspiration can be performed and content sent for pathology to exclude a missed or incomplete abortion.

TREATMENT

Medical therapy: The greatest advance in the management of ectopic pregnancy since Tait has been the development of medical management. In certain carefully selected patients, IM methotrexate can be both safe and effective therapy.

To determine acceptable candidates for methotrexate therapy, first establish the diagnosis by one of the following criteria:

Abnormal doubling rate of beta hCG and sonographic identification of a gestational sac outside of the uterus
Abnormal doubling rate of beta hCG, empty uterus, and menstrual aspiration with no chorionic villi

Once the diagnosis is established, the following criteria also should be met:

Hemodynamically stable
Reliable, compliant patient who will come back for follow-up care
Ectopic pregnancy less than 4 cm in diameter of less than 3.5 cm with cardiac activity
Absence of fetal cardiac activity on ultrasound
No evidence of tubal rupture
Beta hCG less than 6000 IU/L

Criteria 1, 2, and 5 must be met by every patient. Patients who are in excess on criteria 3, 4, or 6 may be candidates for treatment with methotrexate but are expected to have lower success rates than those who meet all the criteria.

On the day of treatment, obtain CBC, creatinine, ALT, AST, and beta hCG levels. Evidence of hepatic or renal compromise contraindicates methotrexate therapy. Blood type, Rh, and antibody screen also are obtained, and all Rh-negative patients are given Rh immunoglobulin. A menstrual aspiration or D & C also should be performed and the sample evaluated for the absence of chorionic villi. If villi are obtained, this is evidence of an abortion and the patient is treated appropriately. If no villi are found, then the patient is a candidate for methotrexate therapy. Persons with experience at floating villi in saline and identifying them under a dissecting microscope can use this procedure. Those without experience may need to wait for histologic confirmation of the absence of villi.

Day 1

Methotrexate (50 mg/m²) is given by IM injection. Advise patients not to take vitamins with folic acid until complete resolution of the ectopic pregnancy has occurred. They also should refrain from alcohol and intercourse for the same period.

Day 4

Patient returns for beta hCG level. This level may be higher than pretreatment level. Day 4 hCG level is the baseline level against which subsequent levels are measured.

Day 7

Draw beta hCG, CBC, and AST levels. If beta hCG has dropped 15% or more since day 4, obtain weekly hCG levels until they have reached the negative level for the lab. If the weekly levels should plateau or increase, a second course of methotrexate may be given.

If beta hCG has not dropped at least 15% from the day 4 level, give a second dose of methotrexate (50 mg/m²) IM on day 7 and observe the patient similarly. If there is no drop by day 14, surgical therapy is indicated.

If the patient develops increasing abdominal pain after methotrexate, repeat a transvaginal scan to evaluate for possible rupture.

Using this protocol, Stovall et al achieved a 96% success rate with a single injection of methotrexate.

Drug Category: Antineoplastics ?Inhibit cell proliferation by destroying rapidly dividing cells.

Drug Name	Methotrexate (Folex, Rheumatrex) ?Acts as a folate antagonist.
Adult Dose	Ectopic pregnancy 50 mg/m² IM on day 1 50 mg/m² IM on day 7, If beta hCG has not dropped at least 15% from day 4 level
Pediatric Dose	Not indicated
Contraindications	Documented hypersensitivity; caution in pregnancy; caution in lactating patients; caution in those with alcohol abuse history; caution in patients with liver dysfunction or infection; caution if patient has impaired liver or renal function or bone marrow depression
Interactions	Combination of acitretin and methotrexate may increase risk of hepatotoxicity; combination of aspirin and methotrexate may increase methotrexate levels; combination of Cox2 Inhibitors and methotrexate may increase methotrexate levels and risk of toxicity; combination of leflunomide and methotrexate may increase risk of hepatotoxicity; NSAIDS, penicillins, probenecid, and salicylates may increase methotrexate levels and risk of toxicity
Pregnancy	D ?Unsafe in pregnancy
Precautions	Caution in those with alcohol abuse history; caution in patients with liver dysfunction or infection; caution if patient has impaired liver or renal function or bone marrow depression

Surgical therapy: Surgical therapy may use either the open laparotomy or laparoscopic route. The choice of route depends on the skill of the surgeon, available equipment, and the condition of the patient.

For example, if at 3:00 am it will take 1 hour to assemble the laparoscopic equipment and the nurse available has never assembled the equipment before, then performing an open laparotomy is much better, especially if the patient is hemodynamically unstable. In many thin patients, a salpingectomy may be performed in 20 minutes through a 3-to 5-cm long suprapubic transverse incision, and the patient can go home the same day. Conversely, in a 350 lb, hemodynamically stable patient, a laparoscopic approach may well be the only way the patient can be discharged in fewer than 5 days.

Consider all of these factors when deciding on the best possible route to approach an ectopic pregnancy.

Preoperative details: If the patient is hemodynamically unstable, obtain large-bore venous access and start fluid resuscitation. Do not delay the operation. The patient has an active bleeding site, and it must be stopped as soon as possible.

Place a Foley catheter prior to starting the procedure.

Either a Hulka tenaculum or a HUMI device inserted into the uterus may be helpful in manipulating the tube during surgery.

Intraoperative details:

Surgical procedures

Regardless of the route of approach, Salpingectomy is indicated in the following situations:

The ectopic has ruptured.
Future fertility is not desired.
This is a sterilization failure.
It is a previously reconstructed tube.
Sterilization is requested.
Hemorrhage continues after salpingotomy.
The ectopic is in the blind ending distal segment after a previous partial salpingectomy.
This is a chronic tubal pregnancy.

In the absence of any of the above indications for salpingectomy, salpingotomy may be performed.

If the ectopic presents at the fimbria, then fimbrial evacuation is feasible, in the absence of indications for salpingectomy.

Partial salpingectomy may be indicated if the pregnancy is in the mid portion of the tube, none of the indications for salpingectomy are present, and the patient may be a candidate for later tubal reanastomosis.

Laparoscopy

Salpingectomy technique

Desiccate the tube between the uterus and the ectopic, utilizing bipolar cautery.
Compress and desiccate the tubo-ovarian artery, while preserving the utero-ovarian artery and ligament.
Cut along the desiccated path, closer to the specimen, leaving a pedicle for hemostasis.
Repeat until the tube is free and can be removed.

Salpingotomy technique

Infiltrate the mesosalpinx with vasopressin (20 IU in 50 ml of NS)(Some authors use on 10IU in 50 ml of NS. Avoid intravascular injection, as it is contraindicated in patients with ischemic heart disease. It frequently causes hypertension.
With the knife or needle electrode, make a 1-to 2-cm incision on the antimesenteric side of the tube.
Insert the aquadissector deep into the incision.
Fluid from the aquadissector under pressure dissects and dislodges the ectopic and clots.
Irrigate the bed well.
If trophoblastic tissue remains, the use of vasopressin may lead to anoxia and death of the trophoblasts, preventing postoperative growth.
Further dissection may damage the tube and usually is not performed.
The products of conception are then removed through the 12-mm sleeve.
If needed, products of conception can be reduced to smaller pieces using biopsy forceps or the aquadissector.
Bleeding may be controlled with pressure from grasping forceps for 5 minutes.
Arterial bleeding may require pinpoint bipolar desiccation.
Diffuse venous bleeding is best controlled with monopolar current. A spark or arc is created using a current of 25-50 W through an electrode in noncontact mode.
Uncontrollable bleeding may require application of an endo loop to provide compression for 10 minutes. The ligature then is released.
If bleeding continues, suture of the mesosalpingeal vessels may be attempted.

Fimbrial evacuation technique

Grasp the fimbria and rotate to allow insertion of the aquadissector.
Fluid under pressure dissects and dislodges ectopic and clots.
Remove the products of conception.

Partial salpingectomy technique

Perform bipolar desiccation across the tube on both sides of the ectopic.
Divide the tube at the sites of desiccation.
The mesosalpinx under the ectopic then can either be desiccated or ligated with an endo loop.
Remove the products of conception.

Laparotomy salpingectomy technique

Clamp the tube between the uterus and the ectopic, using a Pean or similar clamp. Cut the pedicle free and ligate the pedicle with a suture ligature.
Clamp, cut, and ligate the tubo-ovarian artery, while preserving the utero-ovarian artery and ligament.
Continue to clamp cut and ligate the mesosalpinx until the tube is free and can be removed.

Salpingotomy technique

Infiltrate the mesosalpinx with vasopressin (20 IU in 50 cm³ NS). Avoid intravascular injection, as it is contraindicated in patients with ischemic heart disease. It frequently causes hypertension.
With the knife or needle electrode, make a 1-to 2-cm incision on the antimesenteric side of the tube.
Insert the aquadissector, or a syringe filled with saline, deep into the incision.
Fluid from the aquadissector, or syringe, under pressure dissects and dislodges the ectopic and clots.
Irrigate the bed well.
If trophoblastic tissue remains, the prior injection of vasopressin may lead to anoxia and death of the trophoblasts, preventing postoperative growth.
Further dissection may damage the tube and usually is not performed.
Bleeding may be controlled with pressure from blunt tissue forceps for 5 minutes.
Arterial bleeding may require pinpoint bipolar desiccation.
Diffuse venous bleeding is best controlled with monopolar current. A spark or arc is created using a current of 25-50 W through an electrode in noncontact mode.
Uncontrollable bleeding may require application of suture ligature to provide compression for 10 minutes. The ligature then is released.
If bleeding continues, suture of the mesosalpingeal vessels may be attempted.
The tubal incision is left open and not repaired.

Fimbrial evacuation technique

Grasp the fimbria and insert the aquadissector or a syringe filled with saline.
Fluid under pressure dissects and dislodges ectopic and clots.
Remove the products of conception.

Partial salpingectomy technique

Place a clamp through an avascular area in the mesosalpinx under the ectopic. This creates a space through which 2 free ties are places.
Tie the free ties around the tube on each side of the ectopic.
Cut free and remove the isolated portion of the tube containing the ectopic.

Postoperative details: Postoperatively, most patients with an ectopic pregnancy are able to leave the hospital as soon as they have left the recovery room.

In patients who were in shock or had to receive blood transfusions, the postoperative observation should be longer and include observation that the kidneys are functioning normally and the patient has regained normal hemodynamics.

Follow-up care: All patients who have not had the entire ectopic pregnancy removed by salpingectomy need to have their weekly hCG levels observed until they return to nonpregnant levels. If during this time span the hCG level either plateaus or rises, treat with methotrexate.

Patients should all be on some form of effective contraception until such time as their hCG levels have returned to nonpregnant levels.

COMPLICATIONS

While not exactly a complication, cervical pregnancy should be discussed. Cervical pregnancy is an ectopic that has implanted in the cervix. This can cause severe hemorrhage if it starts to separate from the cervix. There are few muscle fibers in the cervix, thus there is no constriction around the hypertrophied blood vessels that developed for the pregnancy. With no pressure on the vessels, profuse hemorrhage can occur.

In recent years, ultrasound diagnosis has improved to the point where the diagnosis is made much more frequently in asymptomatic patients. This leads to many more options in management.
Previously, the only treatment was surgical with curettage of the implantation site. This frequently led to such profuse hemorrhage that surgeons recommended having the patient's abdomen open with ligatures placed around the uterine arteries or hypogastric arteries prior to starting the curettage. Hysterectomy frequently was the result.

Currently, the recommended treatment is either hysterectomy for those who do not desire fertility or methotrexate for those who do desire fertility. Since patients who receive methotrexate occasionally develop severe hemorrhage, observe these patients closely for 1-2 weeks postmethotrexate therapy. An interventional radiologist should be available so that if severe hemorrhage occurs as the pregnancy separates from the cervix, arterial embolization can be performed.

Medical pitfalls

Certain diagnostic pitfalls can occur for the physician sonographer in the diagnosis of ectopic pregnancy.

Low beta hCG levels: Consider beta hCG levels carefully in conjunction with ultrasound findings. Low beta hCG levels may be misleading. Kaplan et al found that 29% of ectopic pregnancies with beta hCG levels less than 1000 IU/L were ruptured. Indeterminate sonographic findings in pregnant patients should prompt further workup despite beta hCG levels.
Location of gestational sac: An ectopic pregnancy may be mistaken for a hemorrhagic corpus luteum cyst or bowel. Advanced ectopics are misdiagnosed as an IUP when the gestational sac and contents have a normal appearance but the sonographer overlooks the extrauterine position of the sac. Employing a systematic approach utilizing the longitudinal and transverse image planes of the uterus and adnexa is mandatory. The ultrasound examination is not complete when an IUP is identified.
Pseudogestational sac: A pseudogestational sac can be confused with a gestational sac or with embryonic demise. An ectopic pregnancy may stimulate the endometrium, causing a fluid collection within the endometrium.
Hemorrhage and hypovolemic shock
Infection
Loss of reproductive organs following surgery
Infertility
Urinary and/or intestinal fistulas following complicated surgery
Disseminated intravascular coagulation

OUTCOME AND PROGNOSIS

The prognosis for patients with an ectopic pregnancy is good for those with an early diagnosis.

Fertility may be conserved in those patients diagnosed with an ectopic pregnancy. The earlier the diagnosis is made and treatment administered, the higher the likelihood of subsequent fertility.

Thirty years ago, when the diagnosis was seldom made prior to rupture, the likelihood of a subsequent normal healthy term pregnancy was only about 35%. Currently, that number is closer to 85%. The difference is in the earlier diagnosis and treatment before the ectopic can grow large enough to severely damage the tube.

PICTURES

Caption: Picture 1. An endovaginal ultrasound revealing an approximate 6-week intrauterine pregnancy. A yolk sac (ys), gestational sac (gs), and fetal pole (fp) are noted.

Picture Type: Photo

Caption: Picture 2. An endovaginal ultrasound demonstrating an early ectopic pregnancy. An echogenic ring (tubal ring) found outside of the uterus can be seen in this view.

Picture Type: Photo

Caption: Picture 3. An endovaginal ultrasound revealing a complex mass outside of the uterus with a small yolk sac present within. The mass is more echogenic than the uterus above and represents an ectopic pregnancy.

Picture Type: Photo

BIBLIOGRAPHY

Abbott J, Emmans LS, Lowenstein SR: Ectopic pregnancy: ten common pitfalls in diagnosis. Am J Emerg Med 1990 Nov; 8(6): 515-22[Medline].
Ackerman TE, Levi CS, Dashefsky SM: Interstitial line: sonographic finding in interstitial (cornual) ectopic pregnancy. Radiology 1993 Oct; 189(1): 83-7[Medline].
Chandra L, Jain A: Maternal serum creatine kinase as a biochemical marker of tubal pregnancy. Int J Gynaecol Obstet 1995 Apr; 49(1): 21-3[Medline].
Cosin JA, Bean M, Grow D: The use of methotrexate and arterial embolization to avoid surgery in a case of cervical pregnancy. Fertil Steril 1997 Jun; 67(6): 1169-71[Medline].
Emerson DS, Cartier MS, Altieri LA: Diagnostic efficacy of endovaginal color Doppler flow imaging in an ectopic pregnancy screening program. Radiology 1992 May; 183(2): 413-20[Medline].
Graham H: Eternal Eve. Eternal Eve 1951; 511-20.
Graham M, Cooperberg PL: Ultrasound diagnosis of interstitial pregnancy: findings and pitfalls. J Clin Ultrasound 1979 Dec; 7(6): 433-7[Medline].
Jafri SZ, Loginsky SJ, Bouffard JA: Sonographic detection of interstitial pregnancy. J Clin Ultrasound 1987 May; 15(4): 253-7[Medline].
Kadar N, DeVore G, Romero R: Discriminatory hCG zone: its use in the sonographic evaluation for ectopic pregnancy. Obstet Gynecol 1981 Aug; 58(2): 156-61[Medline].
Koonin LM, MacKay AP, Berg CJ: Pregnancy-related mortality surveillance--United States, 1987-1990. Mor Mortal Wkly Rep CDC Surveill Summ 1997 Aug 8; 46(4): 17-36[Medline].
Lavie O, Beller U, Neuman M: Maternal serum creatine kinase: a possible predictor of tubal pregnancy [see comments]. Am J Obstet Gynecol 1993 Nov; 169(5): 1149-50[Medline].
Leach RE, Ory SJ: Modern management of ectopic pregnancy [see comments]. J Reprod Med 1989 May; 34(5): 324-38[Medline].
Mateer JR, Aiman EJ, Brown MH: Ultrasonographic examination by emergency physicians of patients at risk for ectopic pregnancy. Acad Emerg Med 1995 Oct; 2(10): 867-73[Medline].
Mateer JR, Valley VT, Aiman EJ: Outcome analysis of a protocol including bedside endovaginal sonography in patients at risk for ectopic pregnancy. Ann Emerg Med 1996 Mar; 27(3): 283-9[Medline].
Stovall TG, Kellerman AL, Ling FW: Emergency department diagnosis of ectopic pregnancy. Ann Emerg Med 1990 Oct; 19(10): 1098-103[Medline].
Stovall TG, Ling FW, Cope BJ: Preventing ruptured ectopic pregnancy with a single serum progesterone. Am J Obstet Gynecol 1989 Jun; 160(6): 1425-8; discussion 1428-31[Medline].
Stovall TG, Ling FW, Gray LA: Single-dose methotrexate for treatment of ectopic pregnancy [see comments]. Obstet Gynecol 1991 May; 77(5): 754-7