Melissa D. Mirosh
Ectopic pregnancy in the adolescent population is fortunately uncommon. Teens usually have not had sufficient time to establish enough exposures to infection or other intraabdominal pathologies to acquire tubal damage and then conceive with resultant ectopic pregnancy. However, in managing ectopic pregnancies in teens, one must remember that access to care may be limited before or after the diagnosis, confidentiality must be respected, future fertility should be protected, and reliable and acceptable contraception should be offered and encouraged during and after treatment.
Ectopic pregnancy should be a consideration when any pregnant adolescent presents for an office visit with new onset of abnormal uterine vaginal bleeding or abdominal/pelvic pain.
Incidence and Prevalence
The risk of ectopic pregnancy in United States is approximately 19 per 1,000 pregnancies, which has remained stable for several years (MMWR, 1995). This is only an approximation because there are many miscarriages, abortions, and medically treated ectopic pregnancies that are not reported.
Etiology and Risk Factors
There are many factors associated with an increased risk of developing an ectopic pregnancy. (Table 56.1)
risk of ectopic pregnancy is significantly reduced in women with an IUD compared with women who use no method of contraception. The current copper IUDs are no longer considered to increase the absolute risk of ectopic pregnancy (Xiong et al., 1995). However, if a patient becomes pregnant with an IUD in situ, the chance that the fetus will implant outside of the uterus is 15% to 20% (Weir, 2003). Progestin-releasing IUDs are associated with an even lower pregnancy rate than nonhormonal IUDs and thereby further reduce the chance of an ectopic pregnancy when compared with sexually active women who are not using contraception (French et al., 2004).
The differential diagnosis of ectopic pregnancy and those teens presenting with acute abdominal or pelvic pain is best divided into obstetrical, gynecological, and nongynecological categories.
The range of symptoms depends on the integrity of the teen's fallopian tube and can range from mild cramping and vaginal spotting to frank hemorrhagic shock. However, the classic triad of vaginal bleeding, delayed menses, and severe lower abdominal pain is associated with tubal rupture and is now a fairly infrequent presentation, because early diagnosis is more routine. In general, there are two distinctly different constellations of signs and symptoms that are expressed by women with ectopic pregnancies, each of which dictates different action plans.
Acute Presentation: Classic, Ruptured Ectopic Pregnancy
Statistically, the teen who presents with a ruptured ectopic pregnancy is more likely to have had a previous pregnancy and therefore usually does not suspect a problem (Saxon et al., 1997). Generally, gestational age at the time of active symptom development varies by the implantation site. For example, ampullary implantations are more likely to rupture at 6 to 8 weeks of gestation, but cornual implantations may not rupture until near the end of the first trimester.
Subacute Presentations: Probable Ectopic Pregnancy and Possible Ectopic Pregnancy
A woman with a positive pregnancy test result who presents with cramping, abnormal vaginal spotting or bleeding, and lower abdominal/adnexal pain should be suspected of having an ectopic pregnancy, particularly if the diagnosis is supported by physical findings of cervical motion tenderness, a closed cervix, adnexal tenderness, and (possibly) an adnexal mass. Women who present in early pregnancy with complaints of vaginal spotting or bleeding and cramping without those suspicious physical findings must also be evaluated to rule out an ectopic pregnancy, although their diagnosis is more likely to be threatened abortion. The work-up and treatment depend on the woman's risk factors and her pregnancy intentions.
The initial diagnosis of a clinically suspected ectopic pregnancy in the hemodynamically stable patient begins with a complete history and physical examination, lab work, and transvaginal ultrasound imaging. If the patient has a regular menstrual cycle, her last menstrual period may be helpful in establishing correct pregnancy dates. Other history that may assist in establishing gestational age includes the date of the first positive pregnancy test result and findings from any previous ultrasonography. The reason for established gestational age is that some authors have recommended using this as a starting point for the diagnostic work-up. In this approach, the first step in the evaluation is an ultrasonography if the gestational age is at least 6 weeks. However, the last menstrual period is often not a reliable or secure data point, particularly in adolescents who may have irregular cycles or imprecise recollections of their menstrual dates. Mol et al. (1998) reviewed 354 patients evaluated for ectopic pregnancy and found that gestational age did not discriminate between intrauterine and ectopic pregnancy. Quantitative β-hCG levels have more reproducibility and, therefore, are used as the basis of most management protocols. The lab work should include CBC count (for white blood cell [WBC], hemoglobin [Hgb], and hematocrit), blood typing, and screening to determine Rh status, and a serum quantitative β-hCG. The adolescent patient may need an explanation for the role of transvaginal ultrasonography as she may be hesitant to have a probe inserted vaginally.
Laboratory and Imaging Evaluation
The properties and limitations of each diagnostic test should be recognized to appropriately use each of them in the work-up.
Outpatient Follow-up—Using Serial β-hCG Levels:
Other Diagnostic Modalities
Issues Unique to Adolescents
Approaches to Management
In the adolescent with an ectopic pregnancy, treatment should generally be fertility-sparing and should take into account that adolescents may have difficulty complying with follow-up recommendations.
Conservative or radical treatment? The most common surgical procedures are salpingostomy and salpingectomy. Unfortunately, there are no randomized controlled studies that directly compare the two. In theory, the benefit of removing the affected tube is an almost guaranteed resolution of the ectopic pregnancy, while treating conservatively preserves the potential for fertility with that tube (which is crucial in adolescents). Five nonrandomized studies have been published that observed the outcomes of conservative versus radical therapy (Bangsgaard et al., 2003; Bouyer et al., 2000; Job-Spira et al., 1996; Mol et al., 1998; Silva et al., 1993). Three of them showed a significant difference in future fertility, but the two more recent studies have implied that conservative surgery may be advantageous with respect to subsequent fertility (Bangsgaard et al., 2003; Bouyer et al., 2000). A randomized controlled trial will likely be needed to complete the debate. Two studies have confirmed that it is not necessary to close the tubal defect after salpingostomy (Fujishita et al., 2004; Tulandi and Saleh, 1999).
There are some patients in whom salpingectomy is the preferred method of treatment. These would include cases of intractable hemorrhage, three recurrent ectopic pregnancies in the same tube, or in women who have completed childbearing. The latter two scenarios seldom occur in the adolescent. One aspect to consider before removing the affected tube is the state of the contralateral tube. If the patient wishes to conserve her chances for spontaneous conception, the unaffected tube must appear normal. If it is abnormal or damaged, salpingostomy for the ectopic pregnancy would be recommended.
Methotrexate: Methotrexate has become an established method of treatment for patients diagnosed with an unruptured ectopic pregnancy. The main advantage of medical therapy over surgical therapy is that it is less invasive and less expensive.
There are no randomized controlled trials comparing single dose to multi-dose treatment. However a meta-analysis found that although a multi-dose regimen is more successful (92.7% versus 88.1%), the overall success of medically treating an ectopic pregnancy with any method of methotrexate is 89% (Barnhart et al., 2003). Often one dose is sufficient (Lipscomb et al., 1998). One study reviewed a group of 55 adolescents who had successfully used the single-dose method and were able to follow the strict follow-up protocols. In this group of teens, the success rate of methotrexate for ectopic pregnancy resolution was 85% (McCord et al., 1996).
Efforts to determine factors that argue favorably for methotrexate therapy identified an initial β-hCG level of <4,000 and lack of fetal cardiac activity as strong predictors of success. Indicators predictive of failure included visible extrauterine yolk sac on ultrasonography and previous ectopic pregnancy (Lipscomb et al., 2004). Patients must be counseled about the possibility of treatment failure (and possible tubal rupture) and the signs and symptoms that may indicate complications and necessitate return to hospital. Because it is common for abdominal pain to occur as the ectopic pregnancy resolves 24 to 48 hours after administration of methotrexate, the differentiation of “normal” from “abnormal” pain can be challenging and may result in additional emergency room visits for reassessment and reassurance.
Gazvani et al., examined the addition of mifepristone to any outpatient regimen of methotrexate and found no benefit (Gazvani et al., 1998).
Other medical modalities: Other medical interventions have included injecting the embryo with methotrexate, hypertonic saline, or prostaglandins. Although successful, these methods are more cumbersome and invasive compared to oral or intramuscular methotrexate, and therefore are much less frequently used (Hajenius et al., 2000; Yao et al., 1996).
Complete resolution of the ectopic pregnancy must be documented because residual trophoblastic tissue proliferation can cause clinical problems. Overall, with salpingostomy, almost 5% of women undergoing laparotomy and 8% to 15% of women who are treated laparoscopically will develop persistent trophoblastic tissue (Seifer et al., 1993). In this situation, it is prudent to ensure that the β-hCG levels return to normal, and another pregnancy should be prevented until that time. β-hCG levels should be measured 6 days postoperatively. If the sixth day value is greater than 15% of the baseline value obtained at the time of surgery, persistent disease is presumed. Some have suggested that postoperative day 1 determinations replace the more delayed follow-up measurements; if day 1 serum β-hCG levels are decreased by 50%, there is an 85% probability that persistent trophoblastic tissue will not occur, and that the patient has been adequately treated (Spandorfer et al., 1997). Expression of ectopic tissue from the end of the fallopian tube (i.e., milking the tube) has been associated with residual disease in up to 25% of cases. Careful postoperative monitoring in these cases is critical.
Obviously, women treated with methotrexate or expectant management will require weekly (or more frequent) quantitative β-hCG determinations until the levels of that hormone become undetectable. Table 56.4 outlines specific guidelines for following up a patient treated with methotrexate.
If persistent disease is diagnosed, further treatment is necessary. If surgical treatment was used initially, methotrexate should probably be used as second line as long as the patient is not continuing to bleed from the ectopic pregnancy. If methotrexate was used initially, options include surgical treatment or repeat methotrexate (Graczykowski and Mishell, 1997). Very occasionally, expectant management can be considered but would again require a well-informed, compliant patient.
It is important to provide your patient effective contraception during her recovery period, not only to prevent a second pregnancy from complicating the β-hCG results, but also to allow the tubal tissue time to heal, thereby presumably reducing the risk of a second ectopic pregnancy in rapid succession. Waiting until the β-hCG levels “zero out” before starting contraception puts a woman in jeopardy for pregnancy because ovulation often precedes complete β-hCG clearance. Assuming the
adolescent is not seeking to conceive, every effort should be made to offer and provide reliable and acceptable contraception to the teen who has had a failed pregnancy (intrauterine or ectopic) or any pregnancy for that matter.
Unsensitized Rh-negative women should be given an appropriate dose of Rh immunoglobulin (50–120 µg if gestational age <12 weeks; 300 µg if >12 weeks) promptly (ACOG, 1999; Fung Kee Fung et al., 2003). Although very occasionally the blood type of the “father” is used to determine whether an Rh-negative woman receives immunoglobulin, it is always prudent to treat the Rh-negative adolescent anyway, because of the uncertainty that may exist with respect to paternity.
Fertility after Treatment of Ectopic Pregnancy
Several studies have looked at ectopic pregnancy recurrence rates and the rates of subsequent intrauterine gestations. On an average, ectopic pregnancies recur in 10% of patients (Bouyer et al., 2002; Pouly et al., 1991). In women seeking pregnancy, reproductive success varies between 50% and 88% within 2 years of the initial ectopic pregnancy (Bangsgaard et al., 2003; Bouyer et al., 2002; Fernandez et al., 1998).
There is no consensus in the literature about the preferred method of surgical treatment with respect to subsequent fertility (Hajenius et al., 2000). Two recent studies suggest that conservative (tube sparing) surgery may lead to a higher intrauterine conception rate than radical (salpingectomy) surgery (Bangsgaard et al., 2003; Fernandez et al., 1998).
Studies looking at fertility after medical treatment of an ectopic pregnancy are also reassuring. Gervaise et al., showed that 64 of 81 women had spontaneous intrauterine pregnancies after local or systemic methotrexate (Gervaise et al., 2004). Fifty-two of these were intrauterine (with 12 spontaneous abortions), and 12 (18%) were recurrent ectopic pregnancies.
Regardless of the method of treatment, adolescent patients who have had only one ectopic pregnancy can be reassured that their chances of having an intrauterine pregnancy in the future are excellent. The method of treatment can therefore be tailored to the needs of the individual patient.
For Teenagers and Parents
http://www.rxmed.com/b.main/b1.illness/b1.illness.html. RxMed Web site providing basic information on ectopic pregnancy.
For Health Professionals
http://emedicine.com/emerg/topic478.htm. eMedicine Web site on ectopic pregnancy.
http://www.aafp.org/afp/20051101/1719ph.html. American Academy of Family Physicians article on ectopic pregnancy.
http://www2.mc.duke.edu/depts/obgyn/ivf/ectopic.htm. Information on ectopic pregnancy from Duke University.
http://www.cmaj.ca/cgi/content/full/173/8/905. Review article on diagnosis and management of ectopic pregnancy from the Canadian Medical Association Journal.
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