Volume 200, Issue 5 , Pages e56-e59, May 2009
Change in quantitative human chorionic gonadotropin after manual vacuum aspiration in women with pregnancy of unknown location
Article Outline
Objective
To determine whether the change in human chorionic gonadotropin after manual vacuum aspiration is predictive of an early abnormal intrauterine pregnancy in women with pregnancy of unknown location.
Study Design
This is a prospective cohort study of 23 clinically stable patients with an early abnormal pregnancy who had abnormally rising human chorionic gonadotropins and absence of sonographic evidence of an intrauterine pregnancy or ectopic pregnancy. The change in human chorionic gonadotropin within 24 hours after manual vacuum aspiration was compared with the pathologic diagnosis and the ultimate clinical diagnosis.
Results
Ten patients had ≥ 50% decrease (mean, 74%; range, 58-80%) in human chorionic gonadotropin after manual vacuum aspiration with confirmed chorionic villi on pathology results. Two patients had a > 50% drop in human chorionic gonadotropin but absence of chorionic villi, clinically consistent with complete spontaneous abortion. The remaining 10 patients who had either rising or < 50% decrease in human chorionic gonadotropin post manual vacuum aspiration all had no chorionic villi on pathology results. The sensitivity, specificity, positive predictive value, and negative predictive value of a ≥ 50% decrease in human chorionic gonadotropin after manual vacuum aspiration in predicting an abnormal intrauterine pregnancy were 92% (95% confidence interval [CI], 0.62-0.99), 100% (95% CI, 0.62-1.0), 100% (95% CI, 0.70-1.0), and 90% (95% CI, 0.54-0.99), respectively.
Conclusion
A ≥ 50% decrease in human chorionic gonadotropin within 24 hours after manual vacuum aspiration is predictive of an abnormal intrauterine pregnancy, thereby excluding an ectopic pregnancy and expediting the management of women with pregnancy of unknown location.
Key words: ectopic pregnancy, human chorionic gonadotropin, manual vacuum aspiration, miscarriage, pregnancy of unknown location
Ectopic pregnancy is a major cause of morbidity and mortality in reproductive-aged women. When a gestational sac is not visualized on transvaginal ultrasound with quantitative human chorionic gonadotropin (hCG) level above the discriminatory zone (1500-2000 mIU/mL),1 the pregnancy is classified as an abnormal intrauterine pregnancy (IUP) or an ectopic pregnancy (EP). A suction uterine dilatation and curettage (D&C) can be performed to assist with the diagnosis, because the presence of chorionic villi confirms an IUP.2 Avoiding uterine evacuation and presuming a diagnosis of an EP can be inaccurate in almost 40% of cases.3
Manual vacuum aspiration (MVA) has been shown to be as efficacious, safe, and tolerable as a D&C for first-trimester and incomplete abortions.4 Moreover, waiting for pathologic diagnosis after uterine evacuation may delay the diagnosis and treatment of EP.
A decrease of greater than 48% in quantitative hCG within 24 hours after a medical abortion is highly predictive of a successful expulsion of an IUP.5, 6 We hypothesize that a decrease of at least 50% in hCG after MVA is predictive of an abnormal IUP in patients with a pregnancy of unknown location (PUL).
Materials and Methods
This is a prospective cohort study approved by the Santa Clara Valley Medical Center Institutional Review Board. Patients with PUL as defined by the following inclusion criteria were recruited: (1) hemodynamically stable and (2) quantitative serum hCG level above 2000 mIU/mL or if under 2000 mIU/mL with abnormally rising levels less than 66% in 48 hours and no evidence of IUP or EP on transvaginal ultrasound by the Radiology Department. Exclusion criteria were as follows: sonographic evidence of EP or IUP including a gestational sac, heavy vaginal bleeding suggestive of passage of “tissue,” or inability to tolerate an outpatient MVA.
An MVA was performed outpatient in a standardized fashion and hCG levels were obtained before and after MVA (within 24 ± 4 hours) procedure. The change in hCG from before and after MVA were compared wth the pathologic diagnosis and the ultimate clinical diagnosis. We calculated the sensitivity, specificity, and positive and negative predictive values of ≥ 50% decrease in hCG compared with the absence or presence of chorionic villi and the ultimate clinical diagnosis of an abnormal IUP.
Results
Between July 2006 and June 2008, 23 patients were enrolled. One patient was excluded because of failure to follow up for post-MVA hCG. The average age of participants was 29 years (range, 21-42 years) with the following ethnicity: Hispanic (87%) and white (13%). The range of gestational age by last menstrual period was from 5-11 weeks. The MVA cannula sizes used ranged from 4-8 mm. The pre-MVA hCG levels ranged from 172-14,485 mIU/mL. Seventeen (73%) patients had serial hCG levels that abnormally rose < 66% in 48 hours, whereas 6 (27%) patients had no evidence of IUP or EP based on pre-MVA hCG levels above the discriminatory zone. Time interval between before and after MVA hCG levels ranged between 16 hours and 47 hours.
Among the 12 patients with ≥ 50% decrease in hCG, 10 (46%) had a confirmation of chorionic villi on pathology results, with an average decline of 74% (median, 70%; range, 58-80%), consistent with an early abnormal IUP (Figure). The other 2 patients, despite a ≥ 50% decrease in hCG, had no chorionic villi, suggestive of passage of tissue of clinical abnormal IUPs as confirmed by the subsequent hCG decline. Among the 10 patients who did not have a ≥ 50% decrease in hCG (range, -1.5% to +40%), none of them had chorionic villi. Three of these patients (hCG change: -8.7%, +9%, and +40%) were treated with laparoscopic salpingectomy based on symptoms with pathologic confirmation of EP. Among the remaining 6 patients, 4 had a rise in post-MVA hCGs (range, 1.5-16%), whereas, 2 had a drop in hCGs of 9% and 17%, respectively. All of them received a single dose of methotrexate for presumed EP, with subsequent appropriate decline in hCG. Interestingly, 1 patient on follow-up ultrasound showed a continued pregnancy after MVA because of evacuation failure. She eventually underwent a suction D&C for an undesired pregnancy. This patient had a pre-MVA hCG of 4535 mIU/mL with a lack of visualization of an IUP or EP. Her hCG rose 25% after MVA to 7035 mIU/mL.
FIGURE.
Results and follow-up of patients after manual vacuum aspiration
a Four patients had an increase in post-MVA hCG and 2 had a < 50% decrease in post-MVA hCG.
hCG, human chorionic gonadotropin, IUP, intrauterine pregnancy, MTX, methotrexate; MVA, manual vaccum aspiration; POC, products of conception; SAB, spontaneous abortion.
Rivera. Change in hGC after MVA in women with PUL. Am J Obstet Gynecol 2009.
A ≥ 50% decrease in hCG when compared with the pathologic diagnosis of chorionic villi had a sensitivity of 100% (95% confidence interval [CI], 0.66-1.0), specificity of 83% (95% CI, 0.51-0.97), positive predictive value of 83% (95% CI, 0.51-0.97), and a negative predictive value of 100% (95% CI, 0.66-1.0) (Table 1). The sensitivity, specificity, positive predictive value, and negative predictive value of a ≥ 50% decrease in hCG after MVA in predicting a clinically abnormal intrauterine pregnancy were 92% (95% CI, 0.62-0.99), 100% (95% CI, 0.62-1.0), 100% (95% CI, 0.70-1.0), and 90% (95% CI, 0.54-0.99), respectively (Table 2). The prevalence of clinical abnormal IUP in this cohort was 54%.
TABLE 1. Sensitivity, specificity, PPV, and NPV of a ≥ 50% decrease in hCG compared with pathology (n = 22)
| Variable | POC+ | POC− | Values |
|---|---|---|---|
| ≥ 50% decrease in hCG | 10 | 2a | PPV = 10/12 (83%) (95% CI, 0.51-0.97) |
| < 50% decrease in hCG | 0 | 10 | NPV = 10/10 (100%) (95% CI, 0.66-1.0) |
Sensitivity = 10/10 (100%) (95% CI, 0.66-1.0) | Specificity = 10/12 (83%) (95% CI, 0.51-0.97) |
aTwo patients had no chorionic villi, suggestive of passage of tissue of clinical abnormal IUPs as confirmed by the subsequent hCG decline. |
TABLE 2. Sensitivity, specificity, PPV, and NPV of a ≥ 50% decrease in hCG compared with clinical diagnosis of an abnormal IUP (n = 22)
| Variable | Clinical abnormal IUP | Presumed ectopic pregnancy | Values |
|---|---|---|---|
| ≥ 50% decrease in hCG | 12 | 0 | PPV = 12/12 (100%) (95% CI, 0.70-0.1.0) |
| < 50% decrease in hCG | 1a | 9 | NPV = 9/10 (90%) (95% CI, 0.54-0.99) |
Sensitivity = 12/13 (92%) (95% CI, 0.62-0.99) | Specificity = 9/9 (100%) (95% CI, 0.62-1.0) |
aThis patient had a continued IUP after manual vacuum aspiration requiring a suction dilatation and curettage for undesired pregnancy. |
Comment
Our study presents a novel approach to evaluating patients with PUL by using a change in 24-hour post-MVA hCG to predict an abnormal IUP. First, instead of a traditional D&C, our protocol uses the less expensive, outpatient MVA for uterine evacuation. Second, using the change in hCG within 24 hours after MVA allows a more expedient method of assessing the pregnancy location. In our design, the MVA pathologic results were not compared with D&C curetting, because the MVA has been documented to be just as effective.4 Our data are further strengthened by the exclusion of sonographic evidence of a gestational sac, which can be mistaken for a pseudo sac.7 Consistent with the literature,3 our cohort confirmed the finding of approximately 40% of women with PUL who would have been treated with methotrexate if MVA were not performed. Furthermore, the majority of patients had more than 2 consecutive hCG values, which failed to have risen minimally using the new redefined hCG curves (53% rise over 2 days).8, 9 Finally, we calculated the diagnostic characteristics of post-MVA hCG change in predicting the presence or absence of chorionic villi as well as clinical abnormal IUP, which is more relevant from a clinical standpoint.
Limitations of our study are the small sample size, the variations in the time interval (range, 16-47 hours) between before and after MVA hCGs, and the potential of incomplete removal of trophoblastic tissue. One patient had a continued pregnancy diagnosed after a rise in post-MVA hCG as a failure to evacuate an early IUP. This finding underscores the importance of serial hCG evaluations and close clinical follow-up after MVA, regardless of the pathologic results. Furthermore, this case also highlights the potential of misclassifying a developing IUP as abnormal when an IUP was not visualized at the currently recommended discriminatory zone of 1500-2000 mIU/mL.10 Moreover, the rate of decline of hCG after an induced abortion was highly variable, depending on the pre-MVA hCG levels. A longer median disappearance time was associated with higher initial level.11 In our cohort, the pre-MVA hCG levels ranged widely, from 172-14,485 mIU/mL. Another potential weakness is that patients with a < 50% drop in hCG were treated with methotrexate for presumed EP without a pathologic confirmation. Under this protocol, treating women with single-dose methotrexate based on lack of villi, the ultimate diagnosis of EP or abnormal IUP cannot be obtained. We acknowledge the possibility of overtreating those 2 patients with falling post-MVA hCG levels. Serial hCG evaluations would have been a preferred treatment option, especially in a population of stable and compliant patients.
Our study has demonstrated a post-MVA hCG drop of ≥ 50% within 24 hours is predictive of an abnormal IUP, thus potentially decreasing the proportion of patients receiving methotrexate for presumed EP. A larger clinical trial is warranted to validate our findings. If confirmed, our algorithm will add to the current armamentarium in the evaluation of patients at risk for EP when the pregnancy location is indeterminate.
References
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- . Manual vacuum aspiration, a safe and effective alternative in early pregnancy termination. Acta Obstet Gynecol Scand. 2001;80:563–567
- Hormone pattern after misoprostol administration for a non-viable first-trimester gestation. Fertil Steril. 2004;81:1099–1105
- . Change in serum beta-human chorionic gonadotropin after abortion with methotrexate and misoprostol. Am J Obstet Gynecol. 1996;174:776–778
- . Ectopic pregnancy diagnosis and the pseudo-sac. Fertil Steril. 2004;81:1225–1228
- Symptomatic patients with an early viable intrauterine pregnancy: HCG curves redefined. Obstet Gynecol. 2004;104:50–55
- Application of redefined human chorionic gonadotropin curves for the diagnosis of women at risk for ectopic pregnancy. Fertil Steril. 2006;86:454–459
- . Suspected ectopic pregnancy. Obstet Gynecol. 2006;107:399–413
- . Plasma human chorionic gonadotropin levels after induced abortion. Adv Contracept. 1996;12:11–14
PII: S0002-9378(08)02026-7
doi:10.1016/j.ajog.2008.10.013
© 2009 Mosby, Inc. All rights reserved.
Volume 200, Issue 5 , Pages e56-e59, May 2009
