Ectopic pregnancy can cause life-threatening hemorrhage, and if it is suspected, the patient should be evaluated and treated as soon as possible. Incidence of ectopic pregnancy is about 2/100 diagnosed pregnancies (1).
1. Van Den Eeden SK, Shan J, Bruce C, Glasser M: Ectopic pregnancy rate and treatment utilization in a large managed care organization. Obstet Gynecol 105 (5 Pt 1):1052–1057, 2015. doi: 10.1097/01.AOG.0000158860.26939.2d
Etiology of Ectopic Pregnancy
Most ectopic pregnancies are located in the fallopian tube, and any history of infection or surgery that increases the risk of tubal adhesions or other abnormalities increases risk of ectopic pregnancy.
Factors that particularly increase risk of ectopic pregnancy include
Prior ectopic pregnancy
Prior abdominal or pelvic surgery, particularly tubal surgery, including tubal ligation
Current intrauterine device (IUD) use
In vitro fertilization in current pregnancy
Pregnancy is much less likely to occur after tubal ligation or IUD placement; however, when pregnancy does occur, risk of ectopic pregnancy is increased (eg, about 5% in current IUD users).
Other risk factors for ectopic pregnancy include
Current use of estrogen/progestin oral contraceptives
History of pelvic inflammatory disease Pelvic Inflammatory Disease (PID) Pelvic inflammatory disease (PID) is a polymicrobial infection of the upper female genital tract: the cervix, uterus, fallopian tubes, and ovaries; abscess may occur. PID may be caused by sexually... read more or sexually transmitted infections Overview of Sexually Transmitted Infections Sexually transmitted infection (STI) refers to infection with a pathogen that is transmitted through blood, semen, vaginal fluids, or other body fluids during oral, anal, or genital sex with... read more (particularly due to Chlamydia trachomatis)
Prior spontaneous or induced abortion
Pathophysiology of Ectopic Pregnancy
The most common site of ectopic implantation is a fallopian tube, followed by the uterine cornua (referred to as a cornual or an interstitial pregnancy). Pregnancies in the cervix, a cesarean delivery scar, an ovary, or the abdomen are rare.
Heterotopic pregnancy (simultaneous ectopic and intrauterine pregnancies) occurs in only 1/10,000 to 30,000 pregnancies but may be more common among women who have had ovulation induction or used assisted reproductive techniques Assisted Reproductive Techniques Assisted reproductive techniques (ARTs) involve manipulation of sperm and ova or embryos in vitro with the goal of producing a pregnancy. For assisted reproductive techniques, oocytes and sperm... read more such as in vitro fertilization and gamete intrafallopian tube transfer (GIFT); in these women, the overall reported ectopic pregnancy rate is 1 to 2% (1 Pathophysiology reference Ectopic pregnancy is the implantation of a pregnancy in a site other than the endometrial lining of the uterine cavity—ie, in the fallopian tube, uterine cornua, cervix, ovary, or abdominal... read more ).
The anatomic structure containing the fetus usually ruptures after about 6 to 16 weeks. Rupture results in bleeding that can be gradual or rapid enough to cause hemorrhagic shock Shock Shock is a state of organ hypoperfusion with resultant cellular dysfunction and death. Mechanisms may involve decreased circulating volume, decreased cardiac output, and vasodilation, sometimes... read more . The later in the pregnancy the rupture occurs, the more rapidly blood is lost and the higher the risk of death.
1. Perkins KM, Boulet SL, Kissin DM, et al: Risk of ectopic pregnancy associated with assisted reproductive technology in the United States, 2001-2011. Obstet Gynecol 125 (1):70–78, 2015. doi: 10.1097/AOG.0000000000000584
Symptoms and Signs of Ectopic Pregnancy
Symptoms of ectopic pregnancy vary and may be absent until rupture occurs.
Most patients have pelvic pain (which can be dull, sharp, or crampy), vaginal bleeding, or both. Patients who have irregular menses may not be aware that they are pregnant.
Rupture may be heralded by sudden, severe pain, followed by syncope or by symptoms and signs of hemorrhagic shock or peritonitis. Rapid hemorrhage is more likely in ruptured cornual pregnancies.
Cervical motion tenderness, unilateral or bilateral adnexal tenderness, or an adnexal mass may be present. Pelvic examination should be done carefully because excessive pressure may rupture the pregnancy. The uterus may be slightly enlarged (but often less than anticipated based on date of the last menstrual period).
Diagnosis of Ectopic Pregnancy
Quantitative serum beta–human chorionic gonadotropin (beta-hCG)
Ectopic pregnancy is suspected in any female of reproductive age with pelvic pain, vaginal bleeding, or unexplained syncope or hemorrhagic shock, regardless of sexual, contraceptive, and menstrual history. Findings of physical (including pelvic) examination are neither sensitive nor specific.
A ruptured ectopic pregnancy is a surgical emergency because it causes maternal hemorrhage and risk of death; prompt diagnosis is essential.
Pearls & Pitfalls
The first step is a urine pregnancy test, which is about 99% sensitive for pregnancy (ectopic and otherwise). If urine beta-hCG is negative and if clinical findings do not strongly suggest ectopic pregnancy, further evaluation is unnecessary unless symptoms recur or worsen. If urine beta-hCG is positive or if clinical findings strongly suggest ectopic pregnancy and pregnancy may be too early to detect based on urine beta-hCG, quantitative serum beta-hCG and pelvic ultrasonography are indicated.
If ultrasonography detects an intrauterine pregnancy, ectopic pregnancy is extremely unlikely except in women who have used assisted reproductive techniques (which increase risk of heterotopic pregnancy, although it is still rare in these patients). However, cornual and interstitial pregnancies may appear to be intrauterine pregnancies. Findings diagnostic for an intrauterine pregnancy are a gestational sac with a yolk sac or an embryo (with or without a heartbeat) within the uterine cavity. In addition to absence of an intrauterine pregnancy, ultrasonographic findings suggesting ectopic pregnancy include a complex (mixed solid and cystic) pelvic mass, particularly in the adnexa, and echogenic free fluid in the cul-de-sac.
If serum beta-hCG is above a certain level (called the discriminatory zone), ultrasonography should detect a gestational sac with a yolk sac in patients with an intrauterine pregnancy. For transvaginal ultrasonography, this level is may be as high as 3500 mIU/mL, although many institutions use 2000 mIU/mL (1 Diagnosis reference Ectopic pregnancy is the implantation of a pregnancy in a site other than the endometrial lining of the uterine cavity—ie, in the fallopian tube, uterine cornua, cervix, ovary, or abdominal... read more ). If the beta-hCG level is higher than the discriminatory zone and an intrauterine pregnancy is not detected, an ectopic pregnancy is likely.
If the beta-hCG level is below the discriminatory zone and ultrasonography is unremarkable, patients may have an early intrauterine pregnancy or an ectopic pregnancy. If clinical evaluation suggests ectopic pregnancy with active bleeding or rupture (eg, signs of significant hemorrhage or peritoneal irritation), diagnostic laparoscopy may be necessary for diagnosis and treatment.
If ectopic pregnancy has not been confirmed and patients are stable, serum levels of beta-hCG are measured serially on an outpatient basis (typically every 2 days). Normally, the level doubles every 1.4 to 2.1 days up to 41 days; in ectopic pregnancy (and in potential spontaneous abortions), levels may be lower than expected by dates and usually do not double as rapidly. If beta-hCG levels do not increase as expected or if they decrease, diagnosis of spontaneous abortion Spontaneous Abortion Spontaneous abortion is pregnancy loss before 20 weeks gestation. Threatened abortion is vaginal bleeding without cervical dilation before 20 weeks in a confirmed viable intrauterine pregnancy... read more or ectopic pregnancy is likely.
1. Connolly AM, Ryan DH, Stuebe AM, Honor M Wolfe HM: Reevaluation of discriminatory and threshold levels for serum β-hCG in early pregnancy. Obstet Gynecol 121 (1):65–70, 2013. doi: 10.1097/aog.0b013e318278f421
Prognosis for Ectopic Pregnancy
Ectopic pregnancy is fatal to the fetus, but if treatment occurs before rupture, maternal death is rare. In the US in 2007, the mortality rate due to ectopic pregnancy was < 1/100.000 women; rates were higher in Black women than in White women and were higher in women > 35 years (1).
1. Creanga AA, Shapiro-Mendoza CK, Bish CL, et al: Trends in ectopic pregnancy mortality in the United States: 1980-2007. Obstet Gynecol 117 (4):837–843 2011. doi: 10.1097/AOG.0b013e3182113c10
Treatment of Ectopic Pregnancy
Usually, methotrexate for small, unruptured ectopic pregnancies
Surgical resection if rupture is suspected or criteria are not met for methotrexate treatment
Rho(D) immune globulin if the woman is Rh-negative
Patients with a tubal pregnancy may be treated with methotrexate if all of the following are present:
The patient is hemodynamically stable with no signs of current or impending rupture.
Complete blood count and renal and liver function test results are normal and the patient has no other contraindications.
The pregnancy is < 3 to 4 cm in diameter.
No fetal heart activity is detected.
The beta-hCG level is ≤ 5,000 mIU/mL.
The patient is willing and able to comply with posttreatment follow-up.
In a commonly used protocol, beta-hCG is measured on day 1, and the patient is given a single dose of methotrexate 50 mg/m2 IM. Beta-hCG measurement is repeated on days 4 and 7. If the beta-hCG level does not decrease by 15% from day 4 to 7, a 2nd dose of methotrexate or surgery is needed. Alternatively, other protocols can be used.
The beta-hCG level is then measured weekly until it is undetectable. Success rates with methotrexate are about 87%; 7% of women have serious complications (eg, rupture).
Usually, methotrexate can be used, but surgery is indicated when rupture is suspected, the patient is not able to comply with follow-up after methotrexate therapy, or methotrexate is ineffective.
Hemodynamically unstable patients require immediate laparotomy and treatment of hemorrhagic shock Treatment of hemorrhagic shock Shock is a state of organ hypoperfusion with resultant cellular dysfunction and death. Mechanisms may involve decreased circulating volume, decreased cardiac output, and vasodilation, sometimes... read more .
For stable patients, surgical treatment is usually laparoscopic surgery; sometimes laparotomy is required. If possible, salpingotomy is done to conserve the tube, and the ectopic pregnancy is removed.
Salpingectomy is indicated in any of the following cases:
The ectopic pregnancy has ruptured.
Hemorrhage continues after salpingotomy.
The tube has been reconstructed.
The ectopic pregnancy represents a failure of a previous sterilization procedure, particularly if the pregnancy is in the blind-ending distal segment in women who have had a previous partial salpingectomy.
The tube has been reconstructed.
Only the irreversibly damaged portion of the tube is removed, maximizing the chance that tubal repair can restore fertility. The tube may or may not be repaired. After a cornual pregnancy, the tube and ovary involved can usually be salvaged, but occasionally repair is impossible, making hysterectomy necessary.
All patients who are Rh-negative, whether managed with methotrexate or surgery, are given Rho(D) immune globulin Prevention .
Ectopic pregnancy is the implantation of a pregnancy in a site other than the endometrial lining of the uterine cavity; the most common site for ectopic pregnancies is a fallopian tube.
Symptoms can include pelvic pain and vaginal bleeding in a pregnant woman, but a women may not be aware she is pregnant and symptoms may be absent until rupture occurs, sometimes with catastrophic results.
Suspect ectopic pregnancy in any female of reproductive age with pelvic pain, vaginal bleeding, or unexplained syncope or hemorrhagic shock.
If a urine pregnancy test is positive or clinical findings suggest ectopic pregnancy, determine quantitative serum beta-hCG and do pelvic ultrasonography.
Treatment usually involves methotrexate, but surgical resection is done if rupture is suspected or criteria are not met for methotrexate treatment.
Drugs Mentioned In This Article
|Drug Name||Select Trade|
human chorionic gonadotropin
|Novarel, Ovidrel, Pregnyl|
|Otrexup, Rasuvo, RediTrex, Rheumatrex, Trexall, Xatmep|