Ectopic Pregnancy

Author: Vicken P Sepilian, MD, MSc; Chief Editor: Michel E Rivlin, MD

http://emedicine.medscape.com/article/2041923-medication#showall

Practice Essentials
Ectopic pregnancy is the result of a flaw in human reproductive physiology that allows the conceptus to implant and mature outside the endometrial cavity, which ultimately ends in the death of the fetus. Without timely diagnosis and treatment, ectopic pregnancy can become a lifethreatening situation.[1]
Essential update: Salpingotomy not superior to salpingectomy for ectopic pregnancy with healthy contralateral tube

In a randomized study involving 446 women with a laparoscopically confirmed tubal pregnancy and a healthy contralateral tube, Mol et al found that salpingotomy did not offer a significant fertility benefit over salpingectomy (though the study results could not exclude the possibility of a very small benefit from the former procedure).[2, 3] For women who underwent salpingotomy, the cumulative ongoing pregnancy rate was 60.7%, compared with 56.2% for those who underwent salpingectomy (P = NS).[3] Persistent trophoblast was observed in 14 women in the salpingotomy group and only 1 woman in the salpingectomy group. Repeat ectopic pregnancy occurred in 8% of women who underwent salpingotomy and 5% of those who underwent salpingectomy.
Signs and symptoms

The classic clinical triad of ectopic pregnancy is as follows:
  

Abdominal pain Amenorrhea Vaginal bleeding

Unfortunately, only about 50% of patients present with all 3 symptoms. Patients may present with other symptoms common to early pregnancy (eg, nausea, breast fullness). The following symptoms have also been reported:
  

Painful fetal movements (in the case of advanced abdominal pregnancy) Dizziness or weakness Fever

   

Flulike symptoms Vomiting Syncope Cardiac arrest

The presence of the following signs suggests a surgical emergency:
   

Abdominal rigidity Involuntary guarding Severe tenderness Evidence of hypovolemic shock (eg, orthostatic blood pressure changes, tachycardia)

Findings on pelvic examination may include the following:
   

The uterus may be slightly enlarged and soft Uterine or cervical motion tenderness may suggest peritoneal inflammation An adnexal mass may be palpated but is usually difficult to differentiate from the ipsilateral ovary Uterine contents may be present in the vagina, due to shedding of endometrial lining stimulated by an ectopic pregnancy

See Clinical Presentation for more detail.
Diagnosis

Serum β-HCG levels In a normal pregnancy, the β-HCG level doubles every 48-72 hours until it reaches 10,00020,000mIU/mL. In ectopic pregnancies, β-HCG levels usually increase less. Mean serum β-HCG levels are lower in ectopic pregnancies than in healthy pregnancies. No single serum β-HCG level is diagnostic of an ectopic pregnancy. Serial serum β-HCG levels are necessary to differentiate between normal and abnormal pregnancies and to monitor resolution of ectopic pregnancy once therapy has been initiated. The discriminatory zone of β-HCG (ie, the level above which an imaging scan should reliably visualize a gestational sac within the uterus in a normal intrauterine pregnancy) is as follows:
 

1500-1800 mIU/mL with transvaginal ultrasonography, but up to 2300 mIU/mL with multiple gestates[4] 6000-6500 mIU/mL with abdominal ultrasonography

Absence of an intrauterine pregnancy on a scan when the β-HCG level is above the discriminatory zone represents an ectopic pregnancy or a recent abortion. Ultrasonography

Ultrasonography is probably the most important tool for diagnosing an extrauterine pregnancy. Visualization of an intrauterine sac, with or without fetal cardiac activity, is often adequate to exclude ectopic pregnancy.[5] Transvaginal ultrasonography, or endovaginal ultrasonography, can be used to visualize an intrauterine pregnancy by 24 days postovulation or 38 days after the last menstrual period (about 1 week earlier than transabdominal ultrasonography). An empty uterus on endovaginal ultrasonographic images in patients with a serum β-HCG level greater than the discriminatory cut-off value is an ectopic pregnancy until proved otherwise. Color-flow Doppler ultrasonography improves the diagnostic sensitivity and specificity of transvaginal ultrasonography, especially in cases in which a gestational sac is questionable or absent. Laparoscopy Laparoscopy remains the criterion standard for diagnosis; however, its routine use on all patients suspected of ectopic pregnancy may lead to unnecessary risks, morbidity, and costs. Moreover, laparoscopy can miss up to 4% of early ectopic pregnancies. Laparoscopy is indicated for patients who are in pain or hemodynamically unstable. See Workup for more detail.
Management

Therapeutic options in ectopic pregnancy are as follows:
  

Expectant management Methotrexate Surgery

Expectant management Candidates for successful expectant management should be asymptomatic and have no evidence of rupture or hemodynamic instability. Candidates should demonstrate objective evidence of resolution (eg, declining β-HCG levels). Close follow-up and patient compliance are of paramount importance, as tubal rupture may occur despite low and declining serum levels of β-HCG. Methotrexate Methotrexate is the standard medical treatment for unruptured ectopic pregnancy. A single-dose IM injection is the more popular regimen. The ideal candidate should have the following:

Image library An endovaginal sonogram demonstrates an early ectopic pregnancy. cornua (2%).7%). Of tubal pregnancies. it also is a preferred method for surgeons inexperienced in laparoscopy and in patients in whom a laparoscopic approach is difficult. See Treatment and Medication for more detail. Background Ectopic pregnancy refers to the implantation of a fertilized egg in a location outside of the uterine cavity. Laparotomy is usually reserved for patients who are hemodynamically unstable or for patients with cornual ectopic pregnancies. including the fallopian tubes (approximately 97.    Hemodynamic stability No severe or persisting abdominal pain The ability to follow up multiple times Normal baseline liver and renal function test results Absolute contraindications to methotrexate therapy include the following:         Existence of an intrauterine pregnancy Immunodeficiency Moderate to severe anemia.) . the ampulla is the most common site of implantation (80%). An echogenic ring (tubal ring) found outside of the uterus can be seen in this view. cornual region of the uterus. ovary. fimbria (5%). or thrombocytopenia Sensitivity to methotrexate Active pulmonary or peptic ulcer disease Clinically important hepatic or renal dysfunction Breastfeeding Evidence of tubal rupture Surgical treatment Laparoscopy has become the recommended surgical approach in most cases. cervix. followed by the isthmus (12%). and abdominal cavity. (See the image below. leukopenia. and interstitia (2-3%).

000 cases in 1970 to 2.4%. Concurrently. (B) Isthmic.5 deaths per 10. 0.Sites and frequencies of ectopic pregnancy.800. By Donna M. Courtesy of Deidra Gundy.2%.) A 12-week interstitial gestation. MD. (See Etiology and Prognosis. 12%. As the gestation enlarges. reporting 17. infertility.000 cases in 1992. 80%. MD. (D) Cornual/Interstitial. RN. it creates the potential for organ rupture. which eventually resulted in a hysterectomy. 5%. which eventually resulted in a hysterectomy. meaning out of place). 1. (C) Fimbrial. (See Epidemiology. (F) Ovarian. the number of ectopic pregnancies had increased to 108. (E) Abdominal. and (G) Cervical. 2%. Department of Obstetrics and Gynecology at Medical College of Pennsylvania and Hahnemann University (MCPHU). Ectopic pregnancies that previously would have resulted in tubal . the Centers for Disease Control and Prevention (CDC) began to record statistics regarding ectopic pregnancy.800 cases. because only the uterine cavity is designed to expand and accommodate fetal development. (A) Ampullary. or death (see the images below). Courtesy of Deidra Gundy. A 12week interstitial gestation. however.6 per 10.2%. In ectopic pregnancy (the term ectopic is derived from the Greek word ektopos.) The increased incidence of ectopic pregnancy has been partially attributed to improved ability in making an earlier diagnosis. By 1992. Peretin. Ectopic pregnancy can lead to massive hemorrhage. the gestation grows and draws its blood supply from the site of abnormal implantation. Department of Obstetrics and Gynecology at Medical College of Pennsylvania and Hahnemann University (MCPHU). the case-fatality rate decreased from 35. 0. In 1970.

physicians will be able to intervene sooner. it has now replaced surgical therapy in many cases. smoking may contribute to decreased tubal motility by damage to the ciliated cells in the fallopian tubes . for example. Some ectopic pregnancies implant in the cervix (< 1%). where over 80% of ectopic pregnancies occur.Which can be the result of infections such as pelvic inflammatory disease (PID) or salpingitis (whether documented or not) or can result from abdominal surgery or tubal ligation or from maternal in utero diethylstilbestrol (DES) exposure History of previous ectopic pregnancy Smoking . 8] As the ability to diagnose ectopic pregnancy improves. it is hoped.abortion or complete. preventing life-threatening sequelae and extensive tubal damage. Many risk factors affect both events.2% each.4% of ectopic pregnancies and ovarian and cervical sites accounting for 0.[6. (See Etiology. or the uterus (as in cases of bicornuate uterus or cesarean delivery scar). or in a rudimentary uterine horn.) Implantation sites The faulty implantation that occurs in ectopic pregnancy occurs because of a defect in the anatomy or normal function of either the fallopian tube (as can result from surgical or infectious scarring). when present. they are not considered normal intrauterine pregnancies. abdominal pregnancies can present at an advanced stage (>28 wk) and have the potential for catastrophic rupture and bleeding. Reflecting this. preserving future fertility.) In the 1980s and 1990s. with abdominal pregnancies accounting for 1. (See Presentation.) Nontubal ectopic pregnancies are a rare occurrence. anything that hampers or delays the migration of the fertilized ovum (blastocyst) to the endometrial cavity can predispose a woman to ectopic gestation.A risk factor in about one third of ectopic pregnancies. DDx. 7.[10] In the absence of modern prenatal care.[11] Etiology An ectopic pregnancy requires the occurrence of 2 events: fertilization of the ovum and abnormal implantation. the most common site is the ampullary portion of the tube. and Workup. ruptured follicle). (See Treatment and Medication. the ovary (as can occur in women undergoing fertility treatments). as well as. Multiple factors contribute to the relative risk of ectopic pregnancy. in previous cesarean delivery scars. most ectopic pregnancies are located in the fallopian tube. spontaneous reabsorption and remained clinically undiagnosed are now detected. medical therapy for ectopic pregnancy was implemented. although these may be technically in the uterus. The following risk factors have been linked to ectopic pregnancy:    Tubal damage .[9] About 80% of ectopic pregnancies are found on the same side as the corpus luteum (the old. a history of major tubal infection decreases fertility and increases abnormal implantation. In theory.

Patients with chlamydial infection have a range of clinical presentations.[14] A 2009 literature review found 56 reported cases of ectopic pregnancy (by definition). History of tubal surgery and conception after tubal ligation Previous tubal surgery has been demonstrated to increase the risk of developing ectopic pregnancy. tubal reanastomosis.to 13-fold increase in the likelihood of another ectopic pregnancy. 13% after 1 episode. and a history of salpingitis increases the risk of ectopic pregnancy 4-fold. a patient with a previous ectopic pregnancy has a 50-80% chance of having a subsequent intrauterine gestation and a 10-25% chance of a future tubal pregnancy. fimbrioplasty. The increase depends on the degree of damage and the extent of anatomic alteration. History of previous ectopic pregnancy After 1 ectopic pregnancy. progesterone-only contraception and progesterone intrauterine devices (IUDs) have been associated with an increased risk of ectopic pregnancy History of 2 or more years of infertility (whether treated or not)[12] . from asymptomatic cervicitis to salpingitis and florid PID. it should have a dramatic impact on the frequency of ectopic pregnancy. Surgeries carrying higher risk of subsequent ectopic pregnancy include salpingostomy.[15] Pelvic inflammatory disease The most common cause of PID is an antecedent infection caused by Chlamydia trachomatis. Once clinically available. The incidence of tubal damage increases after successive episodes of PID (ie. . however. after hysterectomy. Effective vaccination against Chlamydia trachomatis is under investigation. such as Neisseria gonorrhoeae. 75% after 3 episodes). Overall. and lysis of peritubal or periovarian adhesions. most patients presenting with an ectopic pregnancy have no identifiable risk factor. 35% after 2 episodes.    Altered tubal motility . also increase the risk of ectopic pregnancy. dating back to 1937.Women using assisted reproduction seem to have a doubled risk of ectopic pregnancy (to 4%). Other organisms that cause PID. More than 50% of women who have been infected are unaware of the exposure. as well as on the overall health of the female reproductive system.Although this is not an independent risk factor[12] The most logical explanation for the increasing frequency of ectopic pregnancy is previous pelvic infection.As mentioned. this can result from smoking. neosalpingostomy. although this is mostly due to the underlying infertility[13] History of multiple sexual partners[12] Maternal age . but it can also occur as the result of hormonal contraception. a patient incurs a 7.

These mechanisms include one or more of the following: delayed ovulation. However. Studies have demonstrated an elevated risk ranging from 1. among cases of contraceptive failure. or Plan B) does not appear to lead to a higher-thanexpected rate of ectopic pregnancy. The actual incidence of ectopic pregnancies with IUD use is 3-4%.[16] Ectopic pregnancies following tubal sterilizations usually occur 2 or more years after sterilization rather than immediately after. Use of oral contraceptives or an intrauterine device All contraceptive methods lead to an overall lower risk of pregnancy and therefore to an overall lower risk of ectopic pregnancy. however. Failure after bipolar tubal cautery is more likely to result in ectopic pregnancy than is occlusion using suture. A dose-response effect has also been suggested. copper-containing or progesterone IUD traditionally has been thought to be a risk factor for ectopic pregnancy. only about 6% of sterilization failures result in ectopic pregnancy. those who underwent electrocautery and women younger than 35 years were at higher risk. or IUDs and those with a history of tubal ligation. Nevertheless. The modern copper IUD does not increase the risk of ectopic pregnancy. However. This failure is attributed to fistula formation that allows sperm passage.Conception after previous tubal ligation also increases a women's risk of having an ectopic pregnancy. researchers have postulated several mechanisms by which cigarette smoking might play a role in ectopic pregnancies.[17] The presence of an inert. no study has supported a specific mechanism by which cigarette smoking affects the occurrence of ectopic pregnancy. altered tubal and uterine motility.5 times that of nonsmokers. To date.[19] . 35-50% of patients who conceive after a tubal ligation are reported to experience an ectopic pregnancy. In one study. Based on laboratory studies in humans and animals. or clips.6 to 3. if a woman ultimately conceives with an IUD in place. rings. women at increased risk of ectopic pregnancy compared with pregnant controls included those using progestin-only oral contraceptives. and altered immunity. progestin-only implants. 33% of pregnancies occurring after tubal ligation were ectopic. it is more likely to be an ectopic pregnancy. In the first year.[18] Emergency contraception (levonorgestrel. only the progesterone IUD has a rate of ectopic pregnancy higher than that for women not using any form of contraception. Smoking Cigarette smoking has been shown to be a risk factor for ectopic pregnancy development.

but proposed mechanisms include postinflammatory and congenital changes. similar to small diverticula. compared with an incidence of 1 in 30. several million women were exposed in utero to DES. These pockets of epithelium protrude through the tube.[21] Increasing age The highest rate of ectopic pregnancy occurs in women aged 35-44 years. such as those observed with endometriosis.to 4-fold increase in the risk of developing an ectopic pregnancy exists compared with women aged 15-24 years. pregnancies occurring simultaneously in different body sites) dramatically increases when a patient has used assisted reproductive techniques—such as such as in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT)—to conceive. studies have demonstrated that up to 1% of pregnancies achieved through IVF or GIFT can result in a heterotopic gestation. Salpingitis isthmica nodosum Salpingitis isthmica nodosum is defined as the microscopic presence of tubal epithelium in the myosalpinx or beneath the tubal serosa.[20] In a study of 3000 clinical pregnancies achieved through in vitro fertilization. One study demonstrated that infertility patients with luteal phase defects have a statistically higher ectopic pregnancy rate than do patients whose infertility is caused by anovulation.[22] DES exposure Before 1971. spontaneous abortion.Use of fertility drugs or assisted reproductive technology Ovulation induction with clomiphene citrate or injectable gonadotropin therapy has been linked to a 4-fold increase in the risk of ectopic pregnancy in a case-control study. Studies of serial histopathologic 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 ectopic pregnancy rate was 4. as well as acquired tubal changes. which was given to their mothers to prevent pregnancy complications. The etiology of salpingitis isthmica nodosum is unclear.5%.000 pregnancies for spontaneous conceptions. One proposed explanation suggests that aging may result in a progressive loss of myoelectrical activity in the fallopian tube. which is more than double the background incidence. In addition.[23] . and ectopic pregnancy. A 3. myoelectrical activity is responsible for tubal motility. This finding suggests that multiple eggs and high hormone levels may be significant factors. including infertility. Furthermore. In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes. the risk of ectopic pregnancy and heterotopic pregnancy (ie.

000 in 1989[24] but fell to 30. although data there tend to be hospital based rather than derived from nationwide surveys. These statistics are based on data from the US Centers for Disease Control and Prevention (CDC). have made it difficult to reliably monitor incidence (and therefore mortality rates).000 in 1991. An estimated 108. The above data raise the question of whether the number of ectopic pregnancies is declining or whether many ectopic pregnancies are now being treated in ambulatory surgical centers or are even being addressed with medical therapy. failure with progestin-only contraception.6%.7 cases per 1. previous abdominal surgery.Other Other risk factors associated with increased incidence of ectopic pregnancy include anatomic abnormalities of the uterus such as a T-shaped or bicornuate uterus. rates are nearly twice as high for women of other races compared with white women.1-4.[14] Epidemiology Occurrence in the United States The incidence of ectopic pregnancy is reported most commonly as the number of ectopic pregnancies per 1000 conceptions.200 hospitalizations. or approximately 25 cases per 1000 pregnancies. with ectopic pregnancies now accounting for approximately 1-2% of all pregnancies.800 hospitalizations for ectopic pregnancies were reported in 1970.[26] but a review of electronic medical records (inpatient and outpatient) from a large health maintenance organization (HMO) in northern California found a stable rate of 20. In the United States.800 ectopic pregnancies in 1992 resulted in 58. 17. declining to a rate of 9.3 cases per 1.000 in 1998. but truly accurate statistics are lacking. with an estimated cost of $1.1 billion. despite the shift to outpatient treatment.000 in 2000. however. International occurrence The increase in incidence of ectopic pregnancy in the 1970s in the United States was also mirrored in Africa. fibroids or other uterine tumors. Consequently.[27] This suggests that the incidence of ectopic pregnancy in the United States remained steady at about 2% in the 1990s.[28] . Approximately 85-90% of ectopic pregnancies occur in multigravid women. when the reported rate in the United States was 4. which used hospitalizations for ectopic pregnancy to determine the total number of ectopic pregnancies. This number rose to 88. the prevalence is estimated at 1 in 40 pregnancies. without admission. Changes in the management of ectopic pregnancy. the frequency of ectopic pregnancy has increased 6-fold.5 cases per 1000 pregnancies. Some authors believe the latter is true.[25] A review of hospital discharges in California found a rate of 15 cases per 1. with estimates in the range of 1. Since 1970. Looking at raw data. and ruptured appendix.000 reported pregnancies from 1997-2000.

comparing the future reproductive outcomes of the 2 cases would be flawed.and age-related demographics In the United States from 1991 to 1999. which is simpler and avoids the . and tubal surgery Data in the literature have failed to demonstrate substantial and consistent benefit from either salpingostomy or salpingectomy with regard to improving future reproductive outcome.1 per 1. which ultimately ends in the death of the fetus.[1] 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 treatment options.[31] In reporting on 10 years of surgical experience in Paris. Salpingostomy. for selected patients who desire future fertility.000 reported pregnancies from 1997 to 2005. some studies have shown salpingostomy to improve reproductive outcome in patients with contralateral tubal damage. however. thus. For example.6 per 1. using salpingectomy. which includes women from the age of menarche until menopause.[14] Prognosis 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 the endometrial cavity.[30] Any woman with functioning ovaries can potentially have an ectopic pregnancy. A patient with spotting. However.[29] Racial. no abdominal pain.9 for ectopic pregnancy.000 from 1991 to 1993. ectopic pregnancy can become a life-threatening situation. an acute abdomen. despite the risk of persistent ectopic pregnancy. Yao and Tulandi concluded from a literature review that laparoscopic salpingostomy had a reproductive performance that was equal to or slightly better than salpingectomy. and high initial β-HCG levels must be managed surgically. comparing a patient who was managed expectantly with a patient who received methotrexate or with a patient who had a laparoscopic salpingectomy is difficult. Dubuisson et al concluded that. ectopic pregnancy was the cause of 8% of all pregnancyrelated deaths among black women. whereas a patient who presents with hemodynamic instability. These 2 patients probably represent different degrees of tubal damage. Women older than 40 years were found to have an adjusted odds ratio of 2. compared with 9. slightly higher recurrent ectopic pregnancy rates were noted in the salpingostomy group. compared with 4% among white women. Assessment of successful treatment and future reproductive outcome with various treatment options is often skewed by selection bias. salpingectomy. and a low initial beta–human chorionic gonadotropin (β-HCG) level that is falling may be managed expectantly. Without timely diagnosis and treatment.The United Kingdom estimated the incidence of ectopic pregnancy at about 11.

a prospective study of 88 patients by Ory et al indicated that the surgical method had no effect on subsequent fertility in women with an intact contralateral tube.risk of persistent ectopic pregnancy. charred fallopian tube behind after removing the ectopic pregnancy but requiring extensive cautery to control bleeding does not preserve reproductive outcome. is possible and can result in a comparable fertility rate to tubal conservation surgery. and the presence of other risk factors. sparing the affected fallopian tube and thereby improving future reproductive outcome. Leaving a scarred. Maymon et al.[35] Similarly. He also concluded that the more recent studies may reflect an improvement in surgical technique. Salpingectomy by laparotomy carries a subsequent intrauterine pregnancy rate of 25-70%. According to Rulin. after reviewing 20 years of ectopic pregnancy treatment. Parker and Bistis concluded that when the contralateral fallopian tube is normal. 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. compared with laparoscopic salpingectomy rates of 50-60%.[33] In an earlier study. if the treating surgeon has neither the laparoscopic skill nor the instrumentation necessary to atraumatically remove the trophoblastic tissue via linear salpingostomy.[34] The modern pelvic surgeon has been led to believe that the treatment of choice for unruptured ectopic pregnancy is salpingostomy. the subsequent fertility rate is independent of the type of surgery.[37] Future fertility rates have been found to be similar in patients who are treated surgically by laparoscopy or laparotomy. Clausen reviewed literature from the previous 40 years and concluded that only a small number of investigators have suggested. concluded that conservative tubal surgery provided no greater risk of recurrent ectopic pregnancy than the more radical salpingectomy. Very . However. the presence of adhesions. have a more significant impact on future fertility than does the choice of surgical procedure. salpingectomy should be the treatment of choice in women with intact contralateral tubes.[32] Future fertility rates were no different with either surgical approach when the contralateral tube was either normal or scarred but patent. then salpingectomy by laparoscopy or laparotomy is not the wrong surgical choice.[36] Several other studies reported that the status of the contralateral tube. such as endometriosis. that conservative tubal surgery increases the rate of subsequent intrauterine pregnancy. Fertility following surgery Previous history of infertility has been found to be the most significant factor affecting postsurgical fertility. indirectly.

. Comparison of medical and surgical treatment of small. shock. randomized clinical trial also demonstrated the single-dose regimen to have a slightly higher failure rate. 113 patients (94%) were treated successfully. In the United States.8% experienced a subsequent ectopic pregnancy. an estimated 30-40 women die each year from ectopic pregnancy. with some mild adverse effects and lower reproductive outcomes. Other studies have demonstrated similar results.[38] Methotrexate versus surgery The success rates after methotrexate are comparable with laparoscopic salpingostomy. involving 2 equal doses of methotrexate (50 mg/m2) given on days 1 and 4 without the use of leucovorin.3%) of whom needed a second dose. In a study by Stovall and Ling. 87. assuming that the previously mentioned selection criteria are observed. disseminated intravascular coagulopathy (DIC). and death. randomized trial.[38] No adverse effects were encountered. regardless of conservative or radical approach. whereas 12. The average success rates for the single-dosage methotrexate regimen are reported to be from 8894%.1% with the single-dose methotrexate regimen and a success rate of 92. or treatment approach. ranging from 5-20%. with intrauterine pregnancy rates ranging from 20-80%.[38] Other studies have reported similar results. accounting for 913% of all pregnancy-related deaths. Ectopic pregnancy is the leading cause of maternal death in the first trimester.[39] A small. A meta-analysis that included data from 26 trials demonstrated a success rate of 88. Failure to make the prompt and correct diagnosis of ectopic pregnancy can result in tubal or uterine rupture (depending on the location of the pregnancy). The rate of persistent ectopic pregnancy between the 2 groups is also similar.[41] Complications Complications of ectopic pregnancy can be secondary to misdiagnosis. as demonstrated by multiple investigators. The average success rates using the multiple-dosage regimen are in the range of 91-95%.[40] A hybrid protocol.7% with the multiple-dose regimen. late diagnosis.similar rates exist for laparoscopic salpingostomy versus laparotomy. intact extrauterine pregnancies also revealed similar success and subsequent spontaneous pregnancy rates in a prospective. when compared with laparoscopy (6-16%). One study of 77 patients desiring subsequent pregnancy showed intrauterine pregnancies in 64% of these patients and recurrent ectopic pregnancy in 11% of them. A slightly higher recurrent ectopic pregnancy rate exists in patients treated by laparotomy (728%). Furthermore. which in turn can lead to massive hemorrhage.2% of these patients achieved a subsequent intrauterine pregnancy. This surprising finding is believed to be secondary to increased adhesion formation in the group treated by laparotomy. has been shown to be an effective and convenient alternative to the existing regimens. 4 (3.

Mortality In the United States.[30] During 1999–2008.[44] Surveillance data for pregnancy-related deaths in the United States from 1991-1999 showed that ectopic pregnancy was the cause of 5.[29] . However. and obtain the appropriate written consents.000 estimated ectopic pregnancies. second only to venous thromboembolism. The 11 ectopic pregnancy deaths in Florida during 2009-2010 contrasted with the total number of deaths (14) identified in national statistics for 2007. 93% occurred via hemorrhage. bladder.[45] Ectopic pregnancy caused 26% of maternal deaths in early pregnancy in the United Kingdom from 2003-2005.19 deaths per 10.000 live births during 2009-2010. infection. such as the bowel. 2. the World Health Organization (WHO) estimated that ectopic pregnancy was the cause of 4.9% of pregnancy-related deaths in the industrialized world. consider the complications attributable to the surgery.5 deaths per 100. From 1970 to 1989.6% of 4200 maternal deaths. In a review of deaths from ectopic pregnancy in Michigan. There was a high prevalence of illicit drug use among the women who died in Florida. These include bleeding.Any time a surgical approach is chosen as the treatment of choice. In addition to the immediate morbidity caused by ectopic pregnancy. and damage to surrounding organs.6 deaths per 100.5 deaths to 3. 44% of the women who died were either found dead at home or were dead on arrival at the emergency department.8 deaths per 10. the woman's future ability to reproduce may be adversely affected as well.000 ectopic pregnancies.[43] Virtually all ectopic pregnancies are considered nonviable and are at risk of eventual rupture and resulting hemorrhage. and ureters.[28] Using data from 1997 to 2002.000 ectopic pregnancies. these were almost certainly underestimates resulting from underreporting of maternal deaths and misclassification of ectopic pregnancies as induced abortions. the US mortality rate for ectopic pregnancies dropped from 35.035 per 10. then the mortality rate dropped to 3. whether it is laparotomy or laparoscopy. ectopic pregnancy is estimated to occur in 1-2% of all pregnancies and accounts for 3-4% of all pregnancy-related deaths. patients who are diagnosed with ectopic pregnancy before rupture have a low mortality rate and also have a chance at preserved fertility. The CDC reported a higher rate in Florida.[42] It is the leading cause of pregnancy-related mortality during the first trimester in the United States. Infertility may also result secondary to loss of reproductive organs after surgery. Also consider the risks and complications secondary to anesthesia. Make the patient aware of these complications.000 ectopic pregnancies by 1999. and to the major vessels nearby.[24] If the overall incidence of ectopic pregnancy remained stable in the 1990s.[42] The mortality rate reported in African hospital-based studies varied from 50-860 deaths per 10. Of these deaths. despite a relatively low mortality rate of 0.000 live births. the ectopic pregnancy mortality rate in the United States was 0.

Patients with risk factors for ectopic pregnancy should be educated regarding their risk of having an ectopic pregnancy.6% of patients. Birth Control Overview. amenorrhea in 74. amenorrhea.42 for ectopic pregnancy. pain as the presenting symptom is associated with an odds ratio of 1. nonsteroidal anti-inflammatory drugs (NSAIDs). unfortunately. and vaginal bleeding. as well as the need to return to the emergency department for concerning symptoms. see the Pregnancy Center and the Women's Health Center.42. and a method of contacting the physician or the hospital in case of emergency. breast fullness. consecutive case series found no statistically significant differences in the presenting symptoms of patients with unruptured ectopic pregnancies versus those with intrauterine pregnancies.4% of patients.[48] In one study. a prospective. .[46] These symptoms overlap with those of spontaneous abortion. Patients undergoing assisted reproduction technology should be educated regarding their risk of heterotopic pregnancy. a schedule of follow-up visits. Bleeding During Pregnancy. Women who are being discharged with a pregnancy of unknown location should be educated regarding the possibility of ectopic pregnancy and their need for urgent follow-up. as well as Ectopic Pregnancy.[47] In first-trimester symptomatic patients. the pamphlet should include a list of adverse effects. 9% of patients with ectopic pregnancy presented with painless vaginal bleeding. vitamins containing folic acid. Provide an information pamphlet to all patients receiving methotrexate. including nausea. abdominal pain presented in 98. until advised otherwise.1% of them. and 75% may have abdominal tenderness. About 40-50% of patients with an ectopic pregnancy present with vaginal bleeding. fatigue. and sexual intercourse. and Birth Control Methods.Patient Education Advise patients receiving methotrexate therapy to avoid alcoholic beverages. In one case series of ectopic pregnancies. For patient education information. shoulder pain. Painful fetal movements (in the case of advanced abdominal pregnancy). only about 50% of patients present with all 3 symptoms. History The classic clinical triad of ectopic pregnancy is pain. almost 50% of cases of ectopic pregnancy are not diagnosed at the first prenatal visit. dizziness or weakness. Patients may present with other symptoms common to early pregnancy. A signed written consent demonstrating the patient's comprehension of the course of treatment must be obtained. and moderate to severe vaginal bleeding at presentation is associated with an odds ratio of 1. low abdominal pain. heavy cramping.[49] As a result. and recent dyspareunia. 50% have a palpable adnexal mass. and irregular vaginal bleeding in 56. Vaginal Bleeding.

An adnexal mass may be palpated but is usually difficult to differentiate from the ipsilateral ovary. amenorrhea. syncope. and severe tenderness. Patients frequently present with benign examination findings. Shoulder pain may be reflective of peritoneal irritation. this may occur in up to 20% of cases. vomiting. enlarged uterus. which can be caused by shedding of endometrial lining stimulated by an ectopic pregnancy. flulike symptoms. adnexal mass. 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.Usually much worse on the affected side Abdominal rigidity.[51] On pelvic examination. However. The presence of uterine contents in the vagina. and adnexal masses are rarely found. such as orthostatic blood pressure changes and tachycardia. Physical Examination The physical examination of patients with ectopic pregnancy is highly variable and often unhelpful. The most common of these include the following:   Appendicitis Salpingitis . which is highly suggestive of rupture. or cardiac arrest have also been reported.fever. the uterus may be slightly enlarged and soft. midline abdominal tenderness or a uterine size of greater than 8 weeks on pelvic examination decreases the risk of ectopic pregnancy. and vaginal bleeding.[50] Some physical findings that have been found to be predictive (although not diagnostic) for ectopic pregnancy include the following:    Presence of peritoneal signs Cervical motion tenderness Unilateral or bilateral abdominal or pelvic tenderness . or tenderness. as well as evidence of hypovolemic shock. Numerous conditions may have a presentation similar to an extrauterine pregnancy. using modern diagnostic techniques. Fortunately. most ectopic pregnancies may be diagnosed before rupture. and uterine or cervical motion tenderness may suggest peritoneal inflammation. should alert the clinician to a surgical emergency. Approximately 20% of patients with ectopic pregnancies are hemodynamically compromised at initial presentation. involuntary guarding. Patients in hemorrhagic shock from ruptured ectopic may not be tachycardic. may lead to a misdiagnosis of an incomplete or complete abortion and therefore a delayed or missed diagnosis of ectopic pregnancy. Diagnostic Considerations Only 50% of patients with an ectopic pregnancy present with the classic triad of pain.

normal intrauterine pregnancies often present with signs and symptoms similar to those encountered in patients with ectopic pregnancies and other gynecologic or gastrointestinal conditions. The availability of various biochemical. and the specificity was 44%. with a negative likelihood ratio for ruling out tubal rupture of 0. and . A study by Huchon et al found that the following 4 symptoms independently contributed to the diagnosis of tubal rupture:     Vomiting during pain Diffuse abdominal pain Acute pain for longer than 30 minutes Flashing pain The sensitivity was 93% in the presence of 1 or more of these items.16. must also be included in the differential diagnosis. such as degenerating fibroids.[52] The following conditions should also be considered in the differential diagnosis of ectopic pregnancy:        Postabortion bleeding Retained products of abortion Molar pregnancy Cornual myoma or abscess Ovarian tumor Endometrioma Cervical phase of uterine abortion Differential Diagnoses         Abortion Complications Appendicitis Cervical Cancer Dysmenorrhea Early Pregnancy Loss Hemorrhagic Shock Hypovolemic Shock Placenta Previa Approach Considerations Patients with early.    Ruptured corpus luteum cyst or ovarian follicle Spontaneous abortion or threatened abortion Ovarian torsion Urinary tract disease Intrauterine pregnancies with other abdominal or pelvic problems. ultrasonographic.

In a normal pregnancy. serum levels of β-HCG double approximately every 2 days (1. β-HCG levels usually increase less.4-2. healthy intrauterine pregnancies. whereas the lowest adherence (21%) is performing salpingostomy when the other tube is abnormal. screen any female patient in her reproductive years who presents with abdominal pain. or vaginal bleeding for pregnancy. Serum and urine assays for the beta subunit of human chorionic gonadotropin (bhCG) have been developed to detect a pregnancy before the first missed period. Blood type. remember that . the need for a quantitative value makes serum β-HCG the criterion standard for biochemical testing. the β-HCG level doubles every 48-72 hours until it reaches 10. cramping. While some commercial urine test kits are able to detect bhCG in early gestation. Rh type.000mIU/mL. Beta–Human Chorionic Gonadotropin Levels Serum and urine assays for the beta subunit of human chorionic gonadotropin (β-HCG) have been developed to detect a pregnancy before the first missed period. Hence. However. a pregnant patient with a serum β-HCG level of 100 mIU/mL should have a serum β-HCG level of at least 166 mIU/mL 2 days later. the need for a quantitative value makes serum bhCG the criterion standard for biochemical testing. In ectopic pregnancies. In early. and antibody screen should be done in all pregnant patients with bleeding to identify patients in need of RhoGAM and to ensure availability of blood products in case of excessive blood loss.surgical modalities can aid the healthcare provider today in establishing a definitive diagnosis and differentiating among various conditions.[4] For example.[53] The highest adherence is the inclusion of vaginal ultrasonography in the workup (98%).00020. As mentioned earlier. Kadar et al established that the lower limit of the reference range to which serum β-HCG should increase during a 2-day period is 66%. In addition. Evidence-based guidelines have been established for the diagnostic and therapeutic management of ectopic pregnancy. an increase in β-HCG of less than 66% would be associated with an abnormal intrauterine pregnancy or an extrauterine pregnancy. In addition. Rate of increase Serum β-HCG levels correlate with the size and gestational age in normal embryonic growth.1 d). they are associated with varying falsenegative rates. neither risk factors nor signs and symptoms of ectopic pregnancy are sensitive or specific enough to establish a definitive diagnosis. a high index of suspicion is necessary to make a prompt and early diagnosis. they are associated with varying falsenegative rates. In order to reduce the morbidity and mortality associated with ectopic pregnancy. Although some commercial urine test kits are able to detect β-HCG in early gestation. According to Kadar et al’s study.

Furthermore. Another disadvantage is in cases of multiple gestations. no single serum β-HCG level is diagnostic of an ectopic pregnancy. Shepherd et al demonstrated that 64% of very early ectopic pregnancies initially may have normal doubling serum β-HCG levels. Patients with normal multiple gestates were found to have levels of β-HCG above the discriminatory zone before any ultrasonographic evidence of the gestation was apparent. Barnhart et al more reported that the minimum rise in serum β-HCG for a potentially viable pregnancy in women who present with vaginal bleeding or pain is 53% per 2 days (up to 5000 IU/L). even though ectopic pregnancies have been established to have lower mean serum β-HCG levels than healthy pregnancies. additional diagnostic modalities. Discriminatory zone The discriminatory zone of β-HCG is the level above which a normal intrauterine pregnancy is reliably visualized. Drawbacks to β-HCG testing The major disadvantage in relying on serial β-HCG titers to distinguish between normal and abnormal pregnancies is the potential for delay in reaching the diagnosis. Also remember that a discriminatory zone is operator and institution dependent. a gestational sac should be seen within the uterus on transvaginal ultrasonographic images. if a multiple gestation is suspected.15% of healthy intrauterine pregnancies do not increase by 66% and that 13% of all ectopic pregnancies have normally rising β-HCG levels of at least 66% in 2 days. the β-HCG discriminatory zone must be used cautiously. Once β-HCG has reached a level of 700-1000 mIU/mL. intervention when the serum βHCG level rises less than 66% but more than 53% should be undertaken according to other clinical and biochemical criteria. although serial β-HCG titers may be used to differentiate between a normal and an abnormal gestation.[4] and they showed multiple gestations with β-HCG levels of up to 2300 mIU/mL before transvaginal ultrasonographic recognition. Once it has reached 6000 mIU/mL. a gestational sac should be visualized within the uterus on abdominal scan images. are needed. serial serum β-HCG levels are necessary to differentiate between normal and abnormal pregnancies and to monitor resolution of ectopic pregnancy once therapy has been initiated. the clinician must be aware of the zone used by a particular institution before interpreting results there. including ultrasonography and other biochemical markers. Furthermore. Hence.[54] Later. . In short. as in pregnancies resulting from assisted reproduction.[55] Hence. The lack of an intrauterine pregnancy when the β-HCG level is above the discriminatory zone represents an ectopic pregnancy or a recent abortion. the test does little to indicate the location of the pregnancy.

[5] The exception to this is in cases of heterotopic pregnancies.Progesterone Levels A single serum progesterone level is another tool that is useful in differentiating abnormal gestations from healthy intrauterine pregnancies. beta–human chorionic gonadotropin (β-HCG).4% certainty. Furthermore. screening the adnexa by ultrasonography is mandatory even when an intrauterine pregnancy has been visualized. Ultrasonography Ultrasonography is probably the most important tool for diagnosing an extrauterine pregnancy.000 spontaneous pregnancies. and alfafetoprotein (AFP). levels of 5 ng/mL or less indicated a nonviable pregnancy. estriol. is often adequate to exclude ectopic pregnancy. this test is unreliable in differentiating between normal and abnormal pregnancies in patients who conceive after in vitro fertilization (IVF). In one large study. with or without fetal cardiac activity. Several authors have proposed different cutoffs with varying sensitivity and specificity. inhibin. Other Markers Several other serum and urine markers are under investigation to help distinguish normal and abnormal pregnancies. Serum progesterone levels have the following characteristics:     They are not gestational age–dependent They remain relatively constant during the first trimester of normal and abnormal pregnancies They do not return to the reference range if initially abnormal They do not correlate with beta–human chorionic gonadotropin (β-HCG) levels However. and a quadruple screen of serum progesterone. as well as the practice of pharmacologic progesterone supplementation. Also. pregnancy-associated plasma protein A. These markers are usually either early pregnancy proteins or signs of inflammation and damage in smooth muscles and have not been sufficiently sensitive to be useful in clinical medicine. creatinine kinase. pregnanediol glucuronide. ectopic or intrauterine. no consensus on a single progesterone value that differentiates between a normal and an abnormal pregnancy currently exists. and excluded normal pregnancy with 100% sensitivity. Visualization of an intrauterine sac. a progesterone value of greater than 25 ng/mL excluded ectopic pregnancy with 97. Although inexpensive. the usefulness of serum progesterone is limited by the fact that a significant number of results fall in the equivocal range of 5-25 ng/mL. because of excessive progesterone production from multiple corpora lutea. because . placental proteins. which occur in between 1 in 4000 and 1 in 30. These include serum estradiol. In patients undergoing ovarian stimulation and assisted reproduction. although it is more frequently used to confirm an intrauterine pregnancy.

with degeneration of the central decidual reaction. Heterotopic pregnancy is a combined intrauterine and ectopic pregnancy. Structures that represent a developing embryo cannot be recognized until a later time. which is an ultrasonographic term and not an anatomic term. This sac is produced when an ectopic pregnancy stimulates the endometrium. early intrauterine pregnancy. The true gestational sac is located eccentrically within the uterus beneath the endometrial surface. is the first structure that is recognizable on transvaginal ultrasonographic images. Transvaginal/endovaginal ultrasonography Transvaginal ultrasonography. whereas the pseudosac fills the endometrial cavity. with its greater resolution. However. Ultrasonography can also be used to detect the presence of other pathologic conditions that may display the signs and symptoms of ectopic pregnancy. The value of ultrasonography is highlighted further by its ability to demonstrate free fluid in the cul-de-sac. Free fluid on ultrasonographic images can represent physiologic peritoneal fluid or blood from retrograde menstruation and unruptured ectopic pregnancies. A pseudosac is a collection of fluid within the endometrial cavity created by bleeding from the decidualized endometrium and is often associated with an extrauterine pregnancy (see the image below). with positive and negative predictive values of 93% and 99. it is not specific for ruptured ectopic pregnancy. although free fluid can represent hemoperitoneum. or endovaginal ultrasonography.8% respectively. and it may occur in approximately 1 in 30. this should not be mistaken for a normal.000. A pseudogestational sac of ectopic pregnancy can be confused with embryonic demise. can be used to visualize an intrauterine pregnancy by 24 days postovulation or 38 days after the last menstrual period (which is about 1 week earlier than transabdominal ultrasonography can be used for this). This imaging technique can be performed in the outpatient clinic or emergency department and has been reported to have a sensitivity of 90% and a specificity of 99.8%. echogenic rim surrounding a sonolucent center corresponding to the trophoblastic decidual reaction surrounding the chorionic sac. . It has a thick.these patients have a 10-fold increased risk of heterotopic pregnancy.[56] Gestational sac The gestational sac.

or both. or both. without a fetal pole or with a definite fetal pole but without cardiac activity. echogenic rim and a sonolucent center. gestational sac (gs). and fetal pole (fp) are depicted. The embryo is recognized first as a thickening along the edge of the yolk sac.) . brightly echogenic. a gestational sac with a sonolucent center (>5 mm in diameter) is surrounded by a thick. embryonic cardiac motion can be observed at 3. Probable abnormal intrauterine pregnancy In a probable abnormal intrauterine pregnancy. a yolk sac. a yolk sac.5-6 weeks after the last menstrual period. It resembles a distinct circular structure with a bright. echogenic ring located within the endometrium and contains a fetal pole. A yolk sac (ys).5-4 weeks post conception. about 5 weeks after the last menstrual period.) An endovaginal sonogram reveals an intrauterine pregnancy at approximately 6 weeks. (See the image below. ringlike structure is located outside the uterus. concentric. with a gestational sac containing an obvious fetal pole. the gestational sac is larger than 10 mm in diameter. It can first be recognized at 3 weeks post conception. Presumed ectopic pregnancy An empty uterus on endovaginal ultrasonographic images in patients with a serum beta–human chorionic gonadotropin (β-HCG) level greater than the discriminatory cutoff value is an ectopic pregnancy until proven otherwise. Definite ectopic pregnancy In the presence of a definite ectopic pregnancy.The yolk sac is the first visible structure within the gestational sac. Definite intrauterine pregnancy In a definite intrauterine pregnancy. a thick. (See the image below. This is an unusual finding. about 5. This frequently has an irregular or crenelated border. An empty uterus may also represent a recent abortion.

occasionally hematoma). may allow physicians to recognize an early ectopic pregnancy. Interstitial ectopic pregnancy . and/or severe adnexal tenderness with probe palpation may be present. ringlike structure found outside of the uterus that represents an early ectopic pregnancy.An endovaginal sonogram revealing a complex mass outside of the uterus. Other ultrasonographic findings in ectopic pregnancy Findings such as an adnexal mass (usually a corpus luteum. with a small yolk sac present within.[57.) An endovaginal sonogram demonstrates an early ectopic pregnancy. Patients with no definite intrauterine pregnancy and the above-mentioned findings may be at high risk for an ectopic pregnancy. (See the image below. The mass is more echogenic relative to the uterus above and represents an ectopic pregnancy. discussed below. free cul-desac fluid. An echogenic ring (tubal ring) found outside of the uterus can be seen in this view. Tubal ring A tubal ring is an echogenic. Extrauterine mass The presence of a tender adnexal mass on ultrasonographic images suggests an ectopic pregnancy. One study suggested that the presence of any adnexal mass other than a simple cyst was the most significant ultrasonographic finding for the diagnosis of ectopic pregnancy. 58] An appreciation for the spectrum of ultrasonographic findings in ectopic pregnancy.

because the endometrial tissue is more expandable. that level is 6000-6500 mIU/mL. a discriminatory zone of β-HCG levels validates the ultrasonographic findings. the pregnancy generally can be considered extrauterine. At least 5 mm of myometrium should be present. but high-resolution transvaginal ultrasonography has reduced this level to 1500-1800 mIU/mL. These types can grow larger than those within the fallopian tube. With abdominal ultrasonography. if a multiple gestation is suspected.An interstitial ectopic pregnancy implants at the highly vascular region of the uterus near the insertion of the fallopian tube. This is termed the myometrial mantle. an operative approach involving curettage and possible operative laparoscopy was used to diagnose ectopic pregnancy. Barnhart et al reported that 78. The discriminatory zone is the level of β-HCG (using the Third International Standard for quantitative β-HCG) at which all intrauterine pregnancies should be visible on ultrasonography. Findings of a ruptured ectopic pregnancy on ultrasonographic images include free fluid or clotted blood in the cul-de-sac or in the intraperitoneal gutters. the β-HCG discriminatory zone must be used cautiously. along with serum β-HCG levels above the discriminatory zone.[59] . if the patient's serum β-HCG level was above the established discriminatory zone at initial presentation and an intrauterine sac was not identified. they also showed that multiple gestations with β-HCG levels of up to 2300 mIU/mL could be present before transvaginal ultrasonographic recognition.8% of patients were diagnosed definitively at the initial visit using an algorithm that included the use of ultrasonography. Evaluating the amount of uterine myometrium surrounding the gestational sac and echogenic decidual layer is important. Another ultrasonographic finding is the interstitial line sign. the effectiveness of using ultrasonography with a discriminatory zone of β-HCG levels has been well established in the literature. An exception to this is multiple gestations. such as the Morrison pouch. The presence of less than 5mm suggests the diagnosis. Kadar et al reported that patients with normal multiple gestates not only had levels of β-HCG above the discriminatory zone before any ultrasonographic evidence of the gestation was apparent. An aid in the diagnosis of an interstitial ectopic pregnancy is the eccentric location of the gestational sac. Owing to the increased size and partial endometrial implantation. Ultrasonography and discriminatory zone of β-HCG In the absence of reliable menstrual and ovulatory history.[59] In this study. If transvaginal ultrasonography does not reveal an intrauterine pregnancy when the discriminatory β-HCG levels are reached. as in pregnancies resulting from assisted reproduction. Nonetheless. In one large study of more than 1200 patients. Hemosalpinx and ruptured ectopic pregnancy A hemosalpinx is a condition in which the fallopian tubes may fill with blood or free fluid.[4] Therefore. these advanced ectopic pregnancies can be misdiagnosed as intrauterine pregnancies.

or the case may be followed using serial serum β-HCG levels and be treated medically or surgically at a later time. depending on the clinical setting. and from 90% to 99% for viable intrauterine pregnancy. only in cases in which continuation of a pregnancy is not desired even if it were an intrauterine gestation.[59] A discriminatory zone is operator and institution dependent. Dilatation and Curettage A simple way to rule out an ectopic pregnancy is to establish the presence of an intrauterine pregnancy. If the tissue obtained is positive for villi by floating in saline or by histologic diagnosis on frozen or permanent section. Laparoscopy can be performed at that time. Furthermore. ultrasonography was performed. however. obtaining consent for a diagnostic. from 24% to 59% for failed intrauterine pregnancy. the patient's β-HCG levels failed to rise appropriately (ie. The addition of color-flow Doppler ultrasonography may expedite earlier diagnosis and eliminate delays caused by using levels of β-HCG for diagnosis. at least 66% in 2 d). especially in cases in which a gestational sac is questionable or absent. In the absence of villi. this spares the patient exposure to an additional operative procedure.9%. the diagnosis of ectopic pregnancy is made. .[59] If. of course. to exclude the diagnosis of ectopic pregnancy. color-flow Doppler ultrasonography can potentially be used to identify involuting ectopic pregnancies that may be candidates for expectant management. dilatation and curettage can provide a rapid. In a patient undergoing a dilatation and curettage for the diagnosis of ectopic pregnancy. Doppler ultrasonography Color-flow Doppler ultrasonography has been demonstrated to improve the diagnostic sensitivity and specificity of transvaginal ultrasonography. Barnhart et al reported a sensitivity of 100% and a specificity of 99. laparoscopy is also necessary in case the diagnosis of ectopic pregnancy is made.If the patient's serum β-HCG levels were below the discriminatory zone. Once the presence of an abnormal pregnancy has been established by assessing beta– human chorionic gonadotropin (β-HCG) or progesterone levels. increased the diagnostic sensitivity from 71% to 87% for ectopic pregnancy. operative intervention was undertaken with dilatation and curettage or with laparoscopy. With this protocol. cost-effect method to help differentiate between an intrauterine and an ectopic pregnancy. serial β-HCG titers were performed every 2 days. and possibly operative. Once a patient's levels reached the discriminatory zone. This method of diagnostic dilatation and curettage may be used. A study of 304 patients at high risk for ectopic pregnancy found that the use of color-flow Doppler ultrasonography. compared with transvaginal ultrasonography alone. then a nonviable intrauterine pregnancy has occurred. and the clinician must be aware of the zone used by a particular institution before interpreting results.

This procedure is associated with a high false-negative rate (10-14%). the rate of false-negative results with laparoscopy would be expected to rise. Laparoscopy allows assessment of the pelvic structures. can mimic an ectopic pregnancy. laparoscopy can miss up to 4% of early ectopic pregnancies. Moreover. its use today is rare. a ruptured corpus luteum. Laparoscopy remains the criterion standard for diagnosis. Culdocentesis Culdocentesis is another rapid and inexpensive method of evaluation for ruptured ectopic pregnancy. and the presence of other conditions. when present with an intrauterine pregnancy. in which multiple gestations are present. Although culdocentesis is of historic interest. laparoscopy provides the option to treat once the diagnosis is established.Although dilatation and curettage is easy and effective. Furthermore. as more ectopic pregnancies are diagnosed earlier in gestation. the presence of hemoperitoneum (see the image below). usually reflecting blood from an unruptured ectopic pregnancy. it can provide false reassurance in cases of heterotropic pregnancies. because the likelihood of a ruptured ectopic pregnancy is high. operative intervention is indicated. bleeding out of the fimbriated end has resulted in hemoperitoneum. the improved technology with ultrasonographic and hormonal assays is far superior in sensitivity and specificity in reaching the correct diagnosis. the size and exact location of the ectopic pregnancy. Laparoscopy Patients in pain and/or those who are hemodynamically unstable should proceed to laparoscopy. such as ovarian cysts and endometriosis. . When nonclotting blood is found in conjunction with a suspected ectopic pregnancy. and costs. Furthermore. its routine use on all patients suspected of ectopic pregnancy may lead to unnecessary risks. which. or retrograde menstruation. Laparoscopic picture of an unruptured right ampullary tubal pregnancy. with at least 1 being intrauterine and 1 being extrauterine. It is performed by inserting a needle through the posterior fornix of the vagina into the cul-de-sac and attempting to aspirate blood. an incomplete abortion. however. morbidity.

1%. including eliminating morbidity from surgery and general anesthesia. 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 should be asymptomatic and have no evidence of rupture or hemodynamic instability. In the medical treatment group. 15% of cases were categorized as failures and required surgery. With evolving experience with methotrexate. they should demonstrate objective evidence .1% to 35. Some investigators have questioned the need for unnecessary surgical or medical intervention in very early cases and have advocated expectant management in select cases. an obstetrics specialist or a radiologist should be consulted for transvaginal ultrasonography as needed. have led to single-dose outpatient therapy. the treatment of selected ectopic pregnancies has been revolutionized. Medical versus surgical therapy Historically.Approach Considerations Among the greatest advances in the management of ectopic pregnancy has been the development of medical management. Initial protocols for medical therapy required long-term hospitalization and multiple doses of methotrexate and were associated with significant side effects. the treatment of ectopic pregnancy was limited to surgery. However. however. whereas surgical management decreased from approximately 90% to 65%.[6] In this study. Furthermore. potentially less tubal damage.[6] Consultations An obstetrics specialist should be consulted as needed for ectopic pregnancies and for follow-up care of patients with failing/failed intrauterine pregnancies or pregnancies of unknown location. Ectopic pregnancies that previously would have resulted in tubal abortion or complete. Measures of current trends in the management of ectopic pregnancy in the United States from 2002 to 2007 indicated that the percentage of patients treated with methotrexate increased from 11. according to institutional policy. Modification and refinement of these protocols. the authors reported that more than 60% of surgical cases were done laparoscopically and that about 5% of surgical cases required medical therapy. which became available in the mid-1980s. Any patient who is clinically unstable should have the consultation in the emergency department. spontaneous reabsorption and remained clinically undiagnosed are now detected. Medical therapy of ectopic pregnancy is appealing over surgical options for a number of reasons. Furthermore. Expectant Management The increased incidence of ectopic pregnancy is partially attributed to improved ability in making earlier diagnosis. and less cost and need for hospitalization.

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. methotrexate is administered in a single or in multiple intramuscular (IM) injections. By avoiding surgery. Methotrexate has long been known to be effective in the treatment of leukemias. Surgical treatment in these cases is often associated with increased risk of hemorrhage. and bladder. often resulting in hysterectomy or oophorectomy. lymphomas.[60] Successful medical treatment using methotrexate has been reported in the literature with good subsequent reproductive outcomes. cornual. An initial low β-HCG titer also correlates with successful spontaneous resolution. Approximately one fourth of women presenting with ectopic pregnancies have declining β-HCG levels. only 1 of 64 cervical. and carcinomas of the head. Furthermore. The effectiveness of methotrexate on trophoblastic tissue has been well established and is derived from experience gained in using this agent in the treatment of hydatiform moles and choriocarcinomas. Treatment with methotrexate is an especially attractive option when the pregnancy is located on the cervix or ovary or in the interstitial or the cornual portion of the tube. initial β-HCG titers below 1000 mIU/mL have been demonstrated to predict a successful outcome in 88% of cases managed expectantly. Although data are limited on this matter. which is involved in the synthesis of purine nucleotides. making close follow-up and patient compliance of paramount importance.[61] . as long as the gestation is 4cm or less in its greatest dimension. neck. the risk of tubal injury is reduced. ovary. They must also be fully compliant and be willing to accept the potential risks of tubal rupture. breast.of resolution. or cesarean delivery scar pregnancies treated with systemic methotrexate alone or combined with intracardiac injection required surgery. and 70% of this group experience successful outcomes with close observation. As used in the treatment of ectopic pregnancy. This interferes with deoxyribonucleic acid (DNA) synthesis and disrupts cell multiplication. Methotrexate Therapy Methotrexate is an antimetabolite chemotherapeutic agent that binds to the enzyme dihydrofolate reductase. rupture despite low and declining serum levels of β-HCG has been reported. In a study by Verma et al. Note that no cutoff value below which expectant management is uniformly safe has been established. such as declining beta–human chorionic gonadotropin (β-HCG) levels.

Although patients with β-HCG levels above 5.The presence of fetal cardiac activity is a relative contraindication No evidence of tubal rupture .5 cm with cardiac activity) on ultrasonographic measurement . and free fluid in the cul-de-sac on ultrasonographic images (presumably representing tubal rupture) are contraindications to medical therapy with methotrexate. fetal cardiac activity.Evidence of tubal rupture is an absolute contraindication β-HCG level less than 5000 mIU/mL .Higher levels are a relative contraindication Contraindications A β-HCG level of greater than 5. and able to return for follow-up care (must be met by every patient) The size of the gestation should not exceed 4cm at its greatest dimension (or exceed 3.000 IU/L. but not absolute.000 IU/L.000 IU/L and fetal cardiac activity have been treated successfully with methotrexate.Exceeding this size is a relative. To determine acceptable candidates for methotrexate therapy.[62] Other contraindications to the use of methotrexate include the following :        Documented hypersensitivity to methotrexate Breastfeeding Immunodeficiency Alcoholism Alcoholic liver disease Any other type of liver disease Blood dyscrasias . contraindication to medical therapy Absence of fetal cardiac activity on ultrasonographic findings . A systematic review by Menon et al confirmed that there is a substantial increase in failure of medical management of ectopic pregnancy with single-dose methotrexate when the initial β-HCG is above 5. as follows:       The patient must be hemodynamically stable. with no signs or symptoms of active bleeding or hemoperitoneum (must be met by every patient) The patient must be reliable. these patients require much greater surveillance and carry a higher risk of subsequent operative intervention. and menstrual aspiration with no chorionic villi A number of other factors must also be considered once the diagnosis is established. compliant.Indications Medical therapy for ectopic pregnancy involving methotrexate may be indicated in certain patients. There is an inverse association between βHCG levels and successful medical management of an ectopic pregnancy. an empty uterus. first establish the diagnosis by one of the following criteria:   Abnormal doubling rate of the beta–human chorionic gonadotropin (β-HCG) level and ultrasonographic identification of a gestational sac outside of the uterus Abnormal doubling rate of the β-HCG level.

Adverse drug effects include the following:       Nausea Vomiting Stomatitis Diarrhea Gastric distress Dizziness Transient elevation in liver enzymes is also known to occur. hepatic.      Leukopenia Thrombocytopenia Anemia Active pulmonary disease Peptic ulcer disease Renal. heavy vaginal bleeding. including records of telephone calls and certified mail are important medical-legal considerations. and vaginal bleeding or spotting. telephone numbers at home and work. Serious reactions such as bone marrow suppression. Most patients experience at least 1 episode of increased abdominal pain. pneumonitis. It can be differentiated from tubal rupture in that it is milder. which would result in tubal rupture and necessitate surgery. dizziness. the patient must be counseled extensively on the risks. . including the patient's home address. palpitations. Before injection of methotrexate. and they should be advised to contact their physician with significantly worsening abdominal pain or tenderness. pleuritis. or syncope. The physician must emphasize the importance of patient follow-up and have patient information on hand. benefits. tachycardia. Patients should be aware of the signs and symptoms associated with tubal rupture. dermatitis. an increase in β-HCG levels during the first 1-3 days of treatment. and reversible alopecia can occur with higher doses but are rare with doses used in the treatment of ectopic pregnancy. Proper documentation of attempts to reach the patient. and adverse effects of the treatment and on the possibility of failure of medical therapy. or hematologic dysfunction Adverse effects and mandatory patient counseling Adverse effects associated with the use of methotrexate can be divided into adverse drug effects and treatment effects. and the means to reach a contact person in case attempts to reach the patient directly are unsuccessful. which usually occurs 23 days after the injection. Treatment effects of methotrexate include an increase in abdominal pain (occurring in up to two thirds of patients). Increased abdominal pain is believed to be caused by the separation of the pregnancy from the implanted site. of limited duration (lasting 24-48 h). and is not associated with signs of acute abdomen or hemodynamic instability. The medical treatment of ectopic pregnancy requires compulsive compliance.

With smaller dosing and fewer injections. Because of a higher incidence of adverse effects and the increased need for patient motivation and compliance. it decreases the action of methotrexate. Single-dose regimen The more popular regimen today is the single-dose injection. Provide an information pamphlet to all patients receiving methotrexate. and the use of leucovorin can be abandoned.dilatation and curettage. Normal dividing cells preferentially absorb leucovorin. nonsteroidal antiinflammatory drugs (NSAIDs). 2. 5.Advise patients to avoid alcoholic beverages. the same enzyme inhibited by methotrexate. Day 1 Obtain levels of the following:  β-HCG . 3. 4. hence. Studies comparing the multiple methotrexate dosage regimen with the single dosage regimen have demonstrated that the 2 methods have similar efficacy.1 mg/kg on days 1.[8] Day 0 Obtain β-HCG level. This regimen involves administration of methotrexate as 1 mg/kg IM on days 0. and a method of contacting the physician or the hospital in case of emergency. Using this protocol. which involves injection of methotrexate as 50 mg/m2 IM in a single injection or as a divided dose injected into each buttock. a schedule of follow-up visits. followed by 4 doses of leucovorin as 0. and sexual intercourse. and +/. ultrasonography. thereby decreasing methotrexate’s adverse systemic effects. Stovall et al achieved a 96% success rate with a single injection of methotrexate. and 6. A signed written consent demonstrating the patient's comprehension of the course of treatment must be obtained. the pamphlet should include a list of adverse effects. and 7. the multiple dosage regimen has fallen out of favor in the United States. until advised otherwise. Methotrexate Treatment Protocols A number of accepted protocols with injected methotrexate exist for the treatment of ectopic pregnancy. Multiple-dose regimen Initial experience used multiple doses of methotrexate with leucovorin to minimize adverse effects. fewer adverse effects are anticipated. vitamins containing folic acid. The protocol for single-dose methotrexate is detailed below. Leucovorin is folinic acid that is the end product of the reaction catalyzed by dihydrofolate reductase.

and the presence of antibodies. The level may be higher than the pretreatment level.[7] Before initiating therapy. Rh factor. Success was less than 70% with an initial β-HCG level of greater than 15. Patients who are Rh negative should receive Rh immunoglobulin. Determine blood type. and antibody screening are also performed. Day 4 The patient returns for measurement of her β-HCG level. Advise patients not to take vitamins with folic acid until complete resolution of the ectopic pregnancy. If the weekly levels plateau or increase. Based on efficacy studies done by Lipscomb et al. . administer a second IM dose of methotrexate (50 mg/m2) on day 7. Rh status. If the β-HCG level has dropped 15% or more since day 4. obtain weekly β-HCG levels until they have reached the negative level for the lab. They should also refrain from alcohol consumption and intercourse for the same period. If the patient develops increasing abdominal pain after methotrexate therapy. success exceeded 90% for single-dose methotrexate when βHCG levels were less than 5000 mIU/mL but dropped to about 80% when levels were 5-10. Day 7 Draw β-HCG and AST levels and perform a complete blood count (CBC). Treatment monitoring protocols The best predictor of success of medical therapy is the initial β-HCG level.000 mIU/mL. alanine aminotransferase (ALT or serum glutamic-pyruvic transaminase [SGPT]) Blood urea nitrogen (BUN) Creatinine Evidence of hepatic or renal compromise is a contraindication to methotrexate therapy. as well as a baseline β-HCG level. and all Rh-negative patients are given Rh immunoglobulin. surgical therapy is indicated.   Liver function .Eg. If the β-HCG level has not dropped at least 15% from the day-4 level. Methotrexate (50 mg/m2) is administered by IM injection. draw blood to determine baseline laboratory values for renal. If no drop has occurred by day 14. Blood type. and bone marrow function. The day-4 hCG level is the baseline level against which subsequent levels are measured. repeat a transvaginal ultrasonographic scan to evaluate for possible rupture. a second course of methotrexate may be administered. aspartate aminotransferase (AST or serum glutamic-oxaloacetic transaminase [SGOT]). hepatic.000 mIU/mL. and observe the patient similarly.

systemically. obesity. hospitalization time. or massive hemoperitoneum). Investigational Medical Treatments The use of oral methotrexate is under investigation. and locally into the ectopic pregnancy directly. Finally. and convalescence period.[63] The patient's β-HCG levels should be measured weekly. plateau. A decline in β-HCG levels of at least 15% from days 4 to 7 postinjection indicates a successful medical response. Laparoscopy has become the recommended approach in most cases. Although methotrexate has remained the most effective and popular drug used in medical therapy for an ectopic pregnancy. hyperosmolar glucose. such as potassium chloride. An initial increase in β-HCG levels often occurs by the third day and is not a cause for alarm. Laparotomy is usually reserved for patients who are hemodynamically unstable or for patients with cornual ectopic pregnancies. Other effective monitoring protocols have also been reported. Multiple studies have demonstrated that laparoscopic treatment of ectopic pregnancy results in fewer postoperative adhesions than laparotomy. laparoscopy reduces cost. and the advantage of this technique over IM injection remains to be established.Obtain repeat β-HCG levels 4 days and 7 days after the methotrexate injection. and these agents have been administered orally. Failure of medical treatment is defined when β-HCG levels increase. Salpingostomy and Salpingectomy 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. however. it also is a preferred method for surgeons inexperienced in laparoscopy and in patients in whom a laparoscopic approach is difficult (eg. although preliminary reports show promising results. or fail to decrease adequately by 15% from days 4 to 7 postinjection. these studies have yielded inconsistent results. other protocols have been used. as well as their advantage over standard methotrexate protocol. surgical intervention may be warranted. Furthermore. The conservative approaches include linear salpingostomy and milking the pregnancy out of the distal ampulla. laparoscopy is associated with significantly less blood loss and a reduced need for analgesia. The more radical approach includes resecting the segment of the fallopian tube that contains the gestation. These therapies remain experimental at present because the efficacy of such treatments. Direct local injection (salpingocentesis) of methotrexate into the ectopic pregnancy under laparoscopic or ultrasonographic guidance has also been reported in the literature. with or without reanastomosis. . and prostaglandins. mifepristone (RU 486). has not been established. A repeat single dose of methotrexate can also be a viable option after reevaluation of the patients' indications and contraindications (including repeat ultrasonography) for medical therapy. secondary to the presence of multiple dense adhesions. At this time. until they become undetectable. efficacy remains to be established.

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. it must be teased out using forceps or aqua-dissection.) Linear incision being made at the antimesenteric side of the ampullary portion of the fallopian tube. because intravascular injection of vasopressin may precipitate acute arterial hypertension and bradycardia. At this time. Several studies have demonstrated no benefit of primary closure (salpingotomy) over healing by secondary intention (salpingostomy). In cases involving uncontrolled bleeding and hemodynamic instability. the involved tube is identified and freed from surrounding structures. Linear salpingostomy In linear salpingostomy. Occasionally. (See the image below. Total salpingectomy is the procedure of choice in a patient who has completed childbearing and no longer desires fertility. are ideal candidates for linear salpingostomy. in a patient with a history of an ectopic pregnancy in the same tube. conservative treatment methods are avoided in favor of radical surgery. (See the images below. To minimize bleeding. or laser. thus. 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. using a microelectrode. or in a patient with severely damaged tubes. the pregnancy usually protrudes out of the incision and may slip out of the tube. harmonic scalpel. a 1. scissors. Ectopic pregnancies in the ampulla are usually located between the lumen and the serosa and.) .to 2-cm linear incision is made along the antimesenteric side of the tube along the thinnest segment of the gestation. Make sure that the needle is not in a blood vessel by aspirating before injecting. Next. which uses pressurized irrigation to help dislodge the pregnancy.

Segmental tubal resection and total salpingectomy In some cases. Some ampullary pregnancies can be teased out and expressed through the fimbrial end (milking of the tube) by using digital expression. or aqua-dissection. persistent trophoblastic tissue. resection of the tubal segment containing the gestation or a total salpingectomy is preferred over salpingostomy. this approach carries with it a higher rate of bleeding. tubal damage. gestation being teased out after linear salpingostomy. in which the endosalpinx is usually damaged. Take care to minimize the thermal injury to the tube during excision. However.Laparoscopic picture of an ampullary ectopic pregnancy protruding out after a linear salpingostomy was performed. Delayed microsurgical reanastomosis can be performed to reestablish tubal patency if enough healthy fallopian tube is present. These patients do poorly with linear salpingostomy. This is true for isthmic pregnancies. Schematic of a tubal Coagulation of oozing areas may be necessary and can be accomplished using microbipolar forceps. suction. so that an adequate portion of healthy tube remains for the reanastomosis. . starting from the fimbriated end and advancing toward the proximal isthmic portion of the tube. and recurrent ectopic pregnancy (33%). Total salpingectomy can be achieved by progressively coagulating and cutting the mesosalpinx. This portion of the tube is then excised. with particular attention to minimize the damage to the surrounding vasculature. 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. with a high rate of recurrent ectopic pregnancy occurring. The underlying mesosalpinx is also coagulated and excised.

The preferred approach based on the location of the pregnancy varies. take care to minimize blood loss and reduce the potential for retained trophoblastic tissue. In all instances. adhesions. and perform copious irrigation and suctioning to remove any remaining fragments. or in a patient with severely damaged tubes. isthmus Size of the pregnancy Presence of confounding complications 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. ampulla. Postoperative details Proper pain control and hemodynamic stability are important postoperative considerations. interstitium. Preoperative details The optimal surgical management for a patient with an ectopic pregnancy depends on several factors. which can reimplant and persist. The presence of uncontrolled bleeding and hemodynamic instability warrants radical surgery over conservative methods.At this point. overnight admission may be necessary for some patients in order to monitor postoperative bleeding and achieve adequate pain control. Note the condition of the contralateral tube. ruptured or unruptured Condition of the contralateral tube .Ie. however. fully inform the patient of the possibility of a laparotomy with bilateral salpingectomy. history. including the following:        Patient's age. Patients treated by laparotomy are usually hospitalized for a few days. Remove large gestations in an endoscopic bag.Eg. regardless of desired fertility. the presence of adhesions. Intraoperative details Throughout the procedure. patients treated with laparoscopy are discharged on the same day of surgery. . or other pathologic processes because this helps in the postoperative counseling of the patient with regard to future fertility potential. Most often. as previously discussed. the tube is separated from the uterus by coagulating and excising with scissors or laser.Ie. and desire for future fertility History of previous ectopic pregnancy or pelvic inflammatory disease (PID) Condition of the ipsilateral tube . Inspect the peritoneal cavity and remove any detected residual trophoblastic tissue. total salpingectomy is the procedure of choice. tubal occlusion Location of the pregnancy .

[64] The decision to use this agent should be made in conjunction with. Methotrexate is an antineoplastic agent that inhibits cell proliferation by destroying rapidly dividing cells. The average time for β-HCG to clear the system is 2-3 weeks. The ideal candidate for medical treatment should have the following:     Hemodynamic stability No severe or persisting abdominal pain The ability to follow up multiple times Normal baseline liver and renal function test results. ie. salpingostomy. Although most of these cases are caused by incomplete removal of trophoblastic tissue. While resolution without any further intervention is the general rule.000 IU/L. or thrombocytopenia . weekly monitoring of quantitative beta–human chorionic gonadotropin (β-HCG) levels is necessary until the level is zero to ensure that treatment is complete. Contraindications Absolute contraindications to methotrexate therapy include the following:    Existence of an intrauterine pregnancy Immunodeficiency Moderate to severe anemia. but up to 6 weeks can be required. Further medical treatment with methotrexate or surgery in symptomatic patients may be necessary if β-HCG levels do not decline or persist. and a hemoperitoneum is greater than 2 L. The risk of persistent trophoblastic tissue is very significant when a hematosalpinx is greater than 6cm in diameter. The incidence of persistent trophoblastic tissue is greater with higher initial β-HCG levels and is relatively rare with titers of less than 3000 IU/L. if not by.Monitoring After surgical excision of an ectopic gestation. a β-HCG titer is more than 20. the persistence of trophoblastic tissue has been associated with tubal rupture and hemorrhage even in the presence of declining β-HCG levels. Medication Summary The standard medical treatment for unruptured ectopic pregnancy is methotrexate therapy. It acts as a folate antagonist. leukopenia. Some authors have suggested administration of a prophylactic dose of methotrexate after conservative surgery to reduce the risk of persistent ectopic pregnancy. the consulting obstetric specialist. some actually may represent multiple ectopic pregnancies in which only 1 gestation is initially recognized and treated. After tubal-sparing surgical removal of an ectopic pregnancy. This is especially true following treatment with conservative surgery. which carries a 5-15% rate of persistent trophoblastic tissue. a fall in β-HCG levels of less than 20% every 72 hours represents incomplete treatment.

Common side effects include an increase in abdominal girth. and pneumonitis. View full drug information Methotrexate (Trexall. until there is a 15% decline in β-HCG over 2 days. The single-dose regimen consists of 1 dose of methotrexate 50 mg/m2. which reduces side effects) given on alternating days. stomatitis. and another dose of methotrexate 50 mg/m2 if the β-HCG has declined less than 15% between days 4 and 7. if the ectopic pregnancy has fetal heart motion) An initial beta–human chorionic gonadotropin (β-HCG) concentration of greater than 5000 mIU/mL Significant free fluid Fetal cardiac activity Regimen The multiple-dose regimen for methotrexate consists of the administration of daily IM doses of 1 mg/kg. Efficacy and adverse effects Both treatment regimens show an efficacy similar to that of surgical management for unruptured ectopic pregnancies in the ideal patient population. Antimetabolite Class Summary Antimetabolite agents are used to terminate pregnancy. vaginal bleeding or spotting. reversible alopecia. gastrointestinal (GI) symptoms. abdominal pain. and dizziness.     Sensitivity to methotrexate Active pulmonary or peptic ulcer disease Clinically important hepatic or renal dysfunction Breastfeeding Evidence of tubal rupture Relative contraindications that indicate likely failure of methotrexate therapy include the following:     Sonogram findings of an ectopic gestational sac greater than 4cm in size (or 3. Rheumatrex) . Rare side effects include severe neutropenia.5cm. followed by a repeat βHCG measurement at day 4. with leucovorin (folinic acid.[64] Antineoplastics.

It is an important cofactor for the enzymes used in production of red blood cells. Vasopressors Class Summary Vasopressors are used for their alpha1 and beta1 properties and for stimulating vasoconstriction in peripheral circulation. 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. because intravascular injection of vasopressin may precipitate acute arterial hypertension and bradycardia. Make sure that the needle is not in a blood vessel by aspirating before injecting. It allows for purine and pyrimidine synthesis. It is a reduced form of folic acid that does not require enzymatic reduction reaction for activation. such as methotrexate. which reduces adverse effects) is given alternating with methotrexate days. both of which are needed for normal erythropoiesis. To minimize bleeding.Methotrexate is used for the treatment of unruptured tubal pregnancy and for persistent disease after salpingostomy Vitamins Class Summary Vitamins are used to correct folic acid deficiency resulting from use of folic acid antagonists. View full drug information Vasopressin (Pitressin) Vasopressin has vasopressor and antidiuretic hormone (ADH) activity. . until there is a 15% decline in β-HCG over 2 days. the involved tube is identified and freed from surrounding structures. Leucovorin (folinic acid. View full drug information Leucovorin Leucovorin is used with folic acid antagonists. In linear salpingostomy.