Ectopic pregnancy

An ectopic pregnancy cannot be carried to term and eventually ruptures or regresses. In an ectopic pregnancy, implantation occurs outside the uterine cavity - in the fallopian tube (in its intramural part), cervix, ovary, abdomen, or pelvis. Early symptoms and signs include pelvic pain, vaginal bleeding, and tenderness with cervical motion. Syncope or hemorrhagic shock may occur if the tube ruptures. Diagnosis is based on beta-hCG levels and ultrasonography. Treatment is laparoscopic or open surgery or intramuscular methotrexate. [ 1 ]

Epidemiology

The incidence of ectopic pregnancy (overall, 2/100 diagnosed pregnancies) increases with increasing maternal age. Other risk factors include a history of pelvic inflammatory disease (especially due to Chlamydia trachomatis), tubal surgery, previous ectopic pregnancies (risk of recurrence is 10%), cigarette smoking, exposure to diethylstilbestrol, and previous induced abortions. The pregnancy rate with an intrauterine device (IUD) is low, but approximately 5% of such pregnancies are ectopic. Both ectopic and intrauterine pregnancies occur in only 1 in 10,000–30,000 pregnancies, but are more common among women who have had ovulation induction or assisted reproductive technologies such as in vitro fertilization and gamete intrafallopian transfer (GIFT); in such cases, the probability of the said ectopic pregnancy is 1% or less.

According to available data, 95% of ectopic pregnancies develop in the ampulla, funnel, and isthmus of the fallopian tubes. Rarely, implantation occurs in the cervix, on the cesarean section scar, in the ovaries, in the abdominal cavity, and in the small pelvis. Rupture of an ectopic pregnancy leads to bleeding, which can be gradual or intense enough to cause hemorrhagic shock. Intraperitoneal blood causes peritonitis.

The incidence of ectopic pregnancy in the general population is estimated to be 1 to 2% and 2 to 5% in patients who have used assisted reproductive technologies.[ 2 ] Ectopic pregnancies with implantation outside the fallopian tube account for less than 10% of all ectopic pregnancies.[ 1 ] Ectopic pregnancy in a cesarean section scar occurs in 4% of all ectopic pregnancies and in 1 in 500 pregnancies in women who have had at least one cesarean section.[ 3 ] Interstitial ectopic pregnancy occurs in approximately 4% of all ectopic implantation sites and has a morbidity and mortality rate up to 7 times higher than other ectopic implantation sites.

Risk factors

Risk factors associated with ectopic pregnancy include older maternal age, smoking, history of ectopic pregnancy, tubal injury or tubal surgery, previous pelvic infections, DES exposure, IUD use, and assisted reproductive technology.

Older age carries a risk of ectopic pregnancy. Older fallopian tubes are likely to have relatively reduced function, predisposing to delayed oocyte transport. In women with a previous ectopic pregnancy, the risk is ten times higher than in the general population. Women planning in vitro fertilization have an increased risk of developing an ectopic pregnancy with a simultaneous intrauterine pregnancy, a so-called heterotypic pregnancy. The risk is estimated at 1:100 in women planning in vitro fertilization. The risk of developing a heterotopic pregnancy is estimated at 1:100 in women seeking in vitro fertilization.

Symptoms Ectopic pregnancy

Symptoms of ectopic pregnancy vary. Most patients report pelvic pain, sometimes cramping, vaginal bleeding, or both. Menstruation may be absent or may occur on time. Rupture is characterized by sudden, severe pain, accompanied by fainting or symptoms and signs of hemorrhagic shock or peritonitis. Rapid bleeding is more likely with ectopic pregnancy in the rudimentary horn of the uterus.

There may be tenderness with cervical motion, unilateral or bilateral adnexal tenderness, or adnexal swelling. The uterus may be slightly enlarged, but the enlargement is less than expected based on the date of the last menstrual period.

Complications and consequences

Women who present early in pregnancy and have tests suggestive of an ectopic pregnancy are at risk of impaired fetal viability when treated with methotrexate.[ 4 ] Women who receive a single-dose methotrexate regimen are at high risk of treatment failure if hCG levels do not decrease by 15% by days 4 to 7, necessitating a second course of treatment. Women who present with vaginal bleeding and pelvic pain may be diagnosed as having an abortion in progress if the ectopic pregnancy is located in the cervix. The patient may have a cervical ectopic pregnancy and will thus be at risk of hemorrhage and potential hemodynamic instability when dilation and curettage is performed. Complications from treatment extend to treatment failure, as women may present with or develop hemodynamic instability, which may lead to death despite early surgical interventions.

Diagnostics Ectopic pregnancy

Transvaginal ultrasound is the key to diagnosing suspected ectopic pregnancy. Serial studies with transvaginal ultrasound,serum hCG measurements, or both are needed to confirm the diagnosis. The first marker of intrauterine pregnancy on ultrasound is a small cavity eccentrically located in the decidua. Two rings of tissue form around the cavity, making it the "double decidual" sign. This sign usually becomes visible at 5 weeks of gestation on abdominal ultrasound. The yolk becomes visible at this time, but transvaginal ultrasound is required to identify it. The embryonic pole becomes visible on transvaginal examination at about 6 weeks of gestation. Uterine fibroids or a high body mass index may limit the accuracy of ultrasound for detecting early intrauterine pregnancy. MRI may be useful in extreme cases, such as the presence of large obstructing uterine fibroids; however, its sensitivity and specificity require further study, and potential risks from gadolinium contrast exposure require attention.

The best diagnostic confirmation of an ectopic pregnancy is through the detection of a fetal heartbeat outside the uterine cavity on ultrasound. The absence of a detectable fetal heartbeat can be misleading; however, a fetal heartbeat does not develop in all cases of ectopic pregnancy. Additional features of ectopic pregnancy include the detection of a yolk sac with or without a yolk sac in an extrauterine location or the detection of a complex adnexal mass other than the typical appearance of a hemorrhagic corpus luteum. When radiologic examination does not adequately confirm the presence of an ectopic pregnancy, direct visualization of the suspicious mass can be accomplished by diagnostic laparoscopy. Direct laparoscopy may miss very small ectopic pregnancies, cervical pregnancies, or those located in a cesarean section scar.

Ectopic pregnancy is suspected in any woman of reproductive age with pelvic pain, vaginal bleeding, or unexplained syncope or hemorrhagic shock, regardless of sexual, contraceptive, and menstrual history. Clinical examination (including pelvic examination) is not informative enough. Diagnosis requires determination of hCG in urine, this method is sensitive in detecting pregnancy (ectopic and intrauterine) in 99% of cases. If the urine hCG test is negative and ectopic pregnancy is not confirmed by clinical data and symptoms do not recur or worsen, then no further investigation is carried out. If the urine test is positive or the clinical examination indicates ectopic pregnancy, then quantitative determination of hCG in serum and pelvic ultrasonography should be performed. If the quantitative indicator is less than 5 mIU/ml, then ectopic pregnancy can be excluded. Ultrasonographic findings suggestive of ectopic pregnancy (reported in 16-32%) include a complex (mixed solid and cystic) mass, especially in the adnexa; free fluid in the cul-de-sac; and absence of a gestational sac in the uterus on transvaginal examination, especially if the hCG level is greater than 1000-2000 mIU/mL. Absence of an intrauterine sac with hCG levels greater than 2000 mIU/mL indicates the presence of an ectopic pregnancy. Use of transvaginal and color Doppler ultrasonography may improve the diagnosis.

If ectopic pregnancy is unlikely and the patient is compensated, serial hCG measurements can be made on an outpatient basis. The level usually doubles every 1.4-2.1 days until day 41; in ectopic pregnancies (and in abortions) the values may be lower than expected at this time and usually do not double as quickly. If the initial assessment or serial hCG measurements suggest an ectopic pregnancy, diagnostic laparoscopy may be necessary to confirm it. If the diagnosis is unclear, the progesterone level can be measured; if it is 5 ng/mL, a viable intrauterine pregnancy is unlikely.

[ 5 ], [ 6 ], [ 7 ], [ 8 ]

Differential diagnosis

Important differential diagnoses to consider in ectopic pregnancy include internal ovarian torque, tubo-ovarian abscess, appendicitis, hemorrhagic corpus luteum, ruptured ovarian cyst, threatened abortion, incomplete abortion, pelvic inflammatory disease, and urinary calculus. The patient's history and hemodynamic status at clinical presentation will influence the order of these differential diagnoses as well as the tests needed to exclude these diagnoses.

Treatment Ectopic pregnancy

Methotrexate administered intramuscularly or laparoscopically are safe and effective treatments for hemodynamically stable women with ectopic pregnancy. The decision on which method to use is guided by the patient's clinical presentation, laboratory and radiologic data, and informed patient choice after consideration of the risks and benefits of each procedure. Patients with relatively low hCG levels may benefit from a single-dose methotrexate protocol. Patients with higher hCG levels may require two-dose regimens. There is literature indicating that methotrexate treatment does not adversely affect ovarian reserve or fertility. hCG levels should be monitored until pregnancy-free levels are reached after methotrexate administration.

Treatment of hemorrhagic shock is also performed; hemodynamically unstable patients require immediate laparotomy. In compensated patients, laparoscopic surgery is usually performed; however, laparotomy is sometimes required. When possible, salpingotomy is performed, usually with an electrosurgical device or laser, to preserve the tube, and the fertilized egg is evacuated. Salpingectomy is indicated in cases of recurrent ectopic pregnancy and in cases of pregnancy greater than 5 cm, when the tubes are severely damaged, and when future childbearing is not planned. Removal of only the irreparably damaged portion of the tube increases the chance that tubal repair will restore fertility. The tube may be repaired during surgery or not. After pregnancy in a rudimentary horn of the uterus, the tube and involved ovary are usually preserved, but sometimes repair is not possible and hysterectomy is necessary.

Surgical treatment of ectopic pregnancy is indicated when methotrexate cannot be used (e.g., when hCG levels are >15,000 mIU/mL) or when its use is ineffective. Surgical treatment is necessary when patients have any of the following: signs of intra-abdominal bleeding, symptoms suggestive of an ongoing dissectable ectopic mass, or hemodynamic instability.

Surgical treatment, including salpingostomy or salpingectomy, should be guided by the clinical condition, the degree of tubal compromise, and the desire to preserve future reproductive function. In simple terms, salpingectomy involves the removal of a fallopian tube, either partially or completely. Salpingostomy or salpingotomy involves the removal of an ectopic pregnancy through an incision in the fallopian tube, leaving it in place.

Forecast

Ectopic pregnancy is fatal to the fetus, but if treated before rupture, maternal mortality is very rare. In the United States, ectopic pregnancy accounts for 9% of pregnancy-related maternal deaths.

Patients with relatively low beta-hCG levels probably have a more favorable prognosis with regard to successful treatment with single-dose methotrexate.[ 9 ] The more advanced the ectopic pregnancy, the less likely it is that single-dose methotrexate therapy will be sufficient. Patients who present in an emergency or with hemodynamic instability are at higher risk of deterioration such as hemorrhagic shock or other complications in the perioperative period. Prognosis will depend on early recognition and timely intervention. Fertility outcomes with tubal preservation remain controversial, with some data showing no significant difference in intrauterine pregnancy rates when comparing salpingectomy and tubal conservative management.[ 10 ]

Sources

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8. Bobdiwala S, Saso S, Verbakel JY, Al-Memar M, Van Calster B, Timmerman D, Bourne T. Diagnostic protocols for the management of pregnancy of unknown location: a systematic review and meta-analysis. BJOG. 2019 Jan;126(2):190-198.
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