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Evaluating the Role of D&C vs Methotrexate in Etopic or Non-viable Intrauterine Pregnancy
Abstract & Commentary
By Jeffrey T. Jensen, MD, MPH, Editor, Leon Speroff, Professor and Vice Chair for Research, Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.
Synopsis: More than 25% of stable women with elevated levels of hCG and no visible intrauterine pregnancy on ultrasound will have a non-viable intrauterine pregnancy, and not an ectopic.
Source: Chung K, et al. Reevaluating the role of dilation and curettage in the diagnosis of pregnancy of unknown location. Fertil Steril 2011;96:659-662.
The authors performed a retrospective cohort study to evaluate the clinical utility of dilation and curettage (D&C) in diagnosing ectopic pregnancy (EP). They enrolled 321 clinically stable women with early pregnancies considered to be at risk for EP. The cohort included women with: 1) no visible intrauterine pregnancy (IUP) with hCG > 2,000 mIU/mL; 2) abnormal rise in hCG level, defined as < 50% increase in 2 days; or 3) abnormal fall in hCG level, defined as < 20% decline in 2 days that showed either no visible IUP on transvaginal ultrasound or an abnormal hCG trend. If clinical suspicion of EP warranted immediate intervention, only a single hCG value was done. Ultrasound impressions were designated as "suspicious for ectopic pregnancy" in the presence of free fluid, thin endometrial echo complex (EEC); mass without gestational sac; or "probable IUP" when an intrauterine sac was seen without a yolk sac or fetal pole. All ultrasounds were performed at the bedside by gynecology residents.
In the entire cohort, 10.6% had an ultrasound impression of "z"probable IUP," 28.7% were "suspicious for ectopic pregnancy," and 60.7% were "nondiagnostic." All 321 women underwent a diagnostic D&C under conscious sedation and a diagnosis of EP or IUP was made by final pathologic review. Overall, 73.2% of the patients were ultimately diagnosed with an EP and 26.8% were found to have a nonviable IUP. Women with EP had significantly lower initial hCGs (mean 731 mIU/mL, range 11-39,836) than those with nonviable IUPs (mean 2806.5 mIU/mL, range 47–48,810) and were more likely to have had a history of a prior EP, but there was no single level of hCG that excluded IUP. The authors concluded that D&C remains a valuable tool to differentiate EP from nonviable IUP and to avoid misdiagnosis and unnecessary exposure to methotrexate. Although low initial hCG values and ultrasound findings, such as a thin endometrial echo complex and the presence of free fluid, are associated with EP, they are not diagnostic.
As I sit writing this late on a Friday afternoon, I know that around the country many gynecologists are having the uncomfortable experience of needing to follow a stable patient with an abnormal early pregnancy over the weekend. This paper from Kurt Barnhart's group provides useful information on this old problem. Too often, I see women referred from the emergency department or from a primary care colleague with an abnormal pregnancy that has been followed with several ultrasound examinations or a series of quantitative hCG evaluations. Sometimes patients undergo multiple sets of both studies. Few providers consider evaluation of the endometrium to be an important step in diagnosis and treatment.
No one likes to give bad news about a desired early pregnancy, but our job is to be realistic and provide care in the most cost-effective and straightforward fashion. Those of us old enough to remember diagnosing EP in the emergency room with a culdocentesis understand the significance of early diagnosis. Serial determination of quantitative hCG coupled with ultrasound allow us to follow the at-risk pregnancy and offer early intervention for EP before rupture. The use of methotrexate to treat EP medically was another major advance; most early EPs now are managed successfully without surgery. Many providers quickly jump to methotrexate when a diagnosis of EP is suspected because the results with this therapy are best when hCG levels are lowest.1 However, it is important to remember that methotrexate is a potent chemotherapeutic agent with potential for serious complications. Approximately 30% of patients who receive single-dose therapy and 40% of those who receive multidose therapy will experience some type of side effect.2 Methotrexate administration also may result in stomatitis and conjunctivitis, and very rarely bone marrow suppression. Although these complications are rare, the treatment is not without risk.
High-resolution vaginal ultrasound is now commonly available in the office and emergency room setting. The combined use of ultrasound and quantitative hCG can provide great clarity in diagnosis of abnormal pregnancy. I use an hCG threshold of 1000 IU/L as the discriminatory zone for detecting an IUP. In a detailed study by Condous et al,3 the sensitivity and specificity of an hCG level of > 1000 IU/L to detect EP were 21.7% and 87.3%, respectively; for an hCG level of > 1500 IU/L these values were 15.2% and 93.4%, respectively, and for an hCG level of > 2000 IU/L they were 10.9% and 95.2%, so not much is gained by going to a higher level of hCG. If there is an hCG > 1000 and no evidence of an IUP, a diagnosis of EP is more likely. If the value is above 3000, one should always see some evidence of an IUP. The ultrasound finding combined with a single hCG should allow a clinician to rapidly triage a patient into a low- or high-risk group. In this paper, more than 50% of EPs and IUPs were identified on the initial evaluation.
Although this small study was retrospective, it provides some important information about patient management. Even with an apparently normal uterine cavity on ultrasound, an IUP cannot be ruled out. Furthermore, empirically treating women at risk for EP with methotrexate does not reduce complications or significantly save on cost (a cost analysis reported that diagnostic D&C cost $173 to $223 more per patient but had nearly 14% fewer complications with about 6% fewer hospitalizations).1 In the Chung et al paper, the woman with the second thinnest endometrial thickness in this series had an IUP. If a D&C had not been done, she would have been subject to methotrexate unnecessarily.
Obviously a D&C has the risk of complications and is painful. However, in the management of EP it can provide rapid answers. Once an abnormal pregnancy has been diagnosed, emptying the uterus provides additional information. Not only will histology provide a definitive diagnosis, but the procedure also will remove trophoblastic cells and result in a drop in hCG. So consider the stable patient that you are seeing this Friday afternoon. You can treat her with methotrexate today or get another hCG on Sunday and repeat her ultrasound on Monday. Or, you can do an office manual suction evacuation with a small curette and send the tissue to pathology. We do practically all of these with a local anesthetic only. On Monday, you will either have histology or be able to get another quantitative hCG. If the hCG declines by 50% you should feel reassured to await the tissue diagnosis. With this strategy, you will avoid giving methotrexate to about 25% of your patients.