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In ectopic pregnancy, implantation occurs in a site other than the endometrial lining of the uterine cavity—in the fallopian tube, uterine cornua, cervix, ovary, or abdominal or pelvic cavity. Ectopic pregnancies cannot be carried to term and eventually rupture or involute. Early symptoms and signs include pelvic pain, vaginal bleeding, and cervical motion tenderness. Syncope or hemorrhagic shock can occur with rupture. Diagnosis is by measurement of the β subunit of human chorionic gonadotropin and ultrasonography. Treatment is with laparoscopic or open surgical resection or with IM methotrexate.
Incidence of ectopic pregnancy is about 2/100 diagnosed pregnancies.
Etiology
Tubal lesions increase risk. Factors that particularly increase risk include
Other specific risk factors include
Pregnancy is less likely to occur when an IUD is in place; however, about 5% of such pregnancies are ectopic.
Pathophysiology
The most common site of ectopic implantation is a fallopian tube, followed by the uterine cornua. Pregnancies in the cervix, a cesarean delivery scar, an ovary, the abdomen, or fallopian tube interstitium 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 such as in vitro fertilization and gamete intrafallopian tube transfer (GIFT); in these women, the overall reported ectopic pregnancy rate is ≤ 1%.
The structure containing the fetus usually ruptures after about 6 to 16 wk. Rupture results in bleeding that can be gradual or rapid enough to cause hemorrhagic shock. Intraperitoneal blood irritates the peritoneum. The later the rupture, the more rapidly blood is lost and the higher the risk of death.
Symptoms and Signs
Symptoms vary and are often absent until rupture occurs. Most patients have pelvic pain (which is sometimes crampy), vaginal bleeding, or both. Menses may or may not be delayed or missed, and patients 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. The uterus may be slightly enlarged (but often less than anticipated based on date of the last menstrual period).
Diagnosis
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.
The first step is doing a urine pregnancy test, which is about 99% sensitive for pregnancy (ectopic and otherwise). If urine β-hCG is negative and if clinical findings do not strongly suggest ectopic pregnancy, further evaluation is unnecessary unless symptoms recur or worsen. If urine β-hCG is positive or if clinical findings strongly suggest ectopic pregnancy, quantitative serum β-hCG and pelvic ultrasonography are indicated.
If quantitative serum β-hCG is < 5 mIU/mL, ectopic pregnancy is excluded. If ultrasonography detects an intrauterine gestational sac, ectopic pregnancy is extremely unlikely except in women who have used assisted reproductive techniques (which increase risk of heterotopic pregnancy); however, cornual and intra-abdominal pregnancies may appear to be intrauterine pregnancies. Ultrasonographic findings suggesting ectopic pregnancy (noted in 16 to 32%) include complex (mixed solid and cystic) masses, particularly in the adnexa, and free fluid in the cul-de-sac.
If serum β-hCG is above a certain level (called the discriminatory zone), ultrasonography should detect a gestational sac in patients with an intrauterine pregnancy. This level is usually about 2000 mIU/mL. If the β-hCG level is higher than the discriminatory zone and an intrauterine gestational sac is not detected, an ectopic pregnancy is likely. Use of transvaginal and color Doppler ultrasonography may improve detection rates.
If the β-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 (eg, signs of significant hemorrhage or peritoneal irritation), diagnostic laparoscopy may be necessary for confirmation. If ectopic pregnancy appears unlikely and patients are stable, serum levels of β-hCG can be 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 abortions), levels may be lower than expected by dates and usually do not double as rapidly. If β-hCG levels do not increase as expected or if they decrease, the diagnoses of spontaneous abortion and ectopic pregnancy are reconsidered.
Prognosis
Ectopic pregnancy is fatal to the fetus, but if treatment occurs before rupture, maternal death is very rare. In the US, ectopic pregnancy probably accounts for 9% of pregnancy-related maternal deaths.
Treatment
Surgical resection
Hemodynamically unstable patients require immediate laparotomy and treatment of hemorrhagic shock (see Shock and Fluid Resuscitation: Hemorrhagic shock). For stable patients, treatment is usually laparoscopic surgery; sometimes laparotomy is required. If possible, salpingotomy, usually using cautery, high-frequency (harmonic) ultrasound devices, or a laser, is done to conserve the tube, and the products of conception are evacuated.
Salpingectomy is indicated in any of the following cases:
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.
Methotrexate
If unruptured tubal pregnancies are < 3.0 cm in diameter, no fetal heart activity is detected, and the β-hCG level is < 5,000 mIU/mL ideally but up to 15,000 mIU/mL, women can be given a single dose of methotrexate 50 mg/m2 IM. β-hCG measurement and ultrasonography are repeated on about days 4 and 7. If the β-hCG level does not decrease by 15%, a 2nd dose of methotrexate or surgery is needed. Alternatively, the β-hCG level is measured on days 1 and 7, and a 2nd dose of methotrexate is given if the level does not decrease by 25%. About 15 to 20% of women treated with methotrexate eventually require a 2nd dose.
The β-hCG level is measured weekly until it is undetectable. Success rates with methotrexate are about 87%; 7% of women have serious complications (eg, rupture). Surgery is indicated when methotrexate is ineffective.
Last full review/revision February 2010 by Antonette T. Dulay, MD
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