Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, 64239, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Abstract |
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Key words: extra-uterine pregnancy/methotrexate/transvaginal ultrasonography
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Introduction |
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The diagnosis of ectopic pregnancy is currently made by integration of the clinical presentation, sensitive hCG pregnancy tests (in urine and serum) and high-resolution transvaginal ultrasonography (TVUS). The use of TVUS allows both the exclusion of an intrauterine sac and visualization of a suspected adnexal mass even as small as 10 mm (Pisarka and Carson, 1999). The likelihood of detecting an adnexal mass by TVUS in cases with suspected EUP depends partly on the hCG concentration, and is estimated to be 80% (Sadek and Schiotz, 1995
).
The evolution of a reliable, non-surgical diagnostic approach subsequently facilitated the use of medical/conservative management of EUP. Tanaka et al. published the first case report of successful medical treatment of tubal pregnancy with methotrexate (MTX), which has gained considerable popularity and is considered highly effective (Tanaka et al., 1982). The follow-up of women treated by MTX includes primarily serial hCG measurements, whereas repeated TVUS is done only according to clinical indications (Buster and Pisarska, 1999
; Lipscomb et al., 1999
).
The ultrasonographic appearance of a tubal EUP mass treated with MTX was reported only once in a small cohort. Brown et al. described the ultrasonographic appearance of 18 pregnancies treated with a multi-dose MTX protocol and found that the serial TVUS did not alter the management of most patients (Brown et al., 1991). The aims of the present study were to define the effect of single-dose MTX treatment of EUP on its ultrasonographic appearance and, particularly, to test the hypothesis that the ultrasonographic appearance is not predictive of the success of the treatment.
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Materials and methods |
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Eligibility for MTX treatment was described previously (Lipscomb et al., 1999). The study women received i.m. MTX (Abitrexate, Teva, Israel) at a dose of 50 mg per m2 of body surface area. The day on which MTX was injected was considered as day zero. Patients were discharged for outpatient surveillance on either the same or the following day. Serum hCG measurements were performed weekly until the concentration reached 25 mIU/ml. Failure of hCG levels to fall by at least 15% during any successive week resulted in repeated administration of MTX. Surgical intervention was performed for a tubal rupture suspected by unstable haemodynamics, falling haemoglobin or acute severe abdominal pain. Success of treatment and its timing were defined as the time of achievement of an hCG concentration of
25 mIU/ml without surgical intervention. All the women who met these criteria for MTX treatment provided their informed consent for the treatment protocol.
Transvaginal ultrasonography was performed by two gynaecological ultrasonographers, each with at least 10 years experience, using Sonoline Elegra (Siemens Medical System, Munich, Germany) with a vaginal probe of 59 MHz. The size of the mass was calculated by multiplying its two greatest dimensions (measured in cm). The mass included a haematoma that could not be separated from the ectopic mass in 20 ultrasound evaluations. The tube was measured separately in all the other evaluations. Serial TVUS was performed weekly until the hCG concentration was 200 mIU/ml or the size of the ectopic mass declined to 1 cm2. In cases with residual mass, the TVUS was repeated after a period of 35 weeks.
Statistical analysis
Results are given as mean (± SEM). According to power analysis, a total of 50 cases is the minimum required for correlation coefficient = 0.3 to reach significance (alpha = 0.05 and 80% power). All the variables were analysed for the normality of their distribution by the one-sample KolmogorovSmirnov test procedure. A significant difference was defined using the two-sided paired t-test. Correlations were calculated using the Pearsons correlation test. All statistics were performed using SPSS for windows version 8.0 (SPSS Inc, Chicago, IL, USA).
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Results |
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Ectopic tubal mass was identified on TVUS in 45 (80%) of women and had a mean size of 4 ± 0.5 cm2. Most of the masses (38 cases, 84%) in this series were primarily solid. The correlation between ectopic size and initial hCG level was r = 0.17 (not significant by the Pearson test). Free fluids were identified in the pouch of Douglas in 38 women (68%). Eight of the eleven cases without identifiable ectopic mass had free fluids in the pouch of Douglas as the only sign of EUP.
Following the first week of MTX injection, the mean size of the ectopic mass increased significantly (to 6 ± 0.8 cm2, P = 0.02) and free fluid was identified in 40 women (71%). An increase in the ectopic mass was observed in 25 women (55%), mostly (23 women) in the first week (92%). No significant correlations were observed between the size of the ectopic mass and subsequent hCG concentration at 1, 2 or 3 weeks following the MTX injection (r = 0.001, 0.2 and 0.2 respectively). The initial and subsequent increase in the size of the ectopic mass was not related to the success of the treatment.
Ectopic mass was identified by sonography before initiation of MTX in all six cases in which MTX failed and surgery was performed. Ultrasonographic resolution of the ectopic mass was documented in all of the remaining 39 women. The resolution of the mass was observed in 27 women (69%) before or with normalization of hCG, following a mean of 42 ± 2.4 days (range 763 days). The other 12 still had a residual mass with a mean size of 11 ± 3.8 cm2 (range 2.139 cm2) at the time of hCG normalization. Complete resolution of the tubal mass in the last 12 women took a further 44 ± 4.3 days (range 2863 days).
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Discussion |
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The role of TVUS in the management of cases with suspected EUP includes the capability to exclude the presence of an intrauterine gestational sac and, at the same time, to identify an adnexal mass, as well as to determine the eligibility for conservative management, mostly MTX treatment. According to the findings of the present study, the rate of detection of tubal mass in cases with ectopic pregnancy was 80%, which concurs with previous reports (Fleischer et al., 1990; Sadek and Schiotz, 1995
). One can argue that the ectopic mass in the 11 cases in which the ectopic pregnancy was not identified by TVUS could be in the cervix, ovary or elsewhere. In any event, however, these were not the focus of our study.
The conclusions of the present study are that a weekly TVUS follow-up of the size of the ectopic mass or the amount of free fluids has limited, if any, diagnostic value following MTX treatment of EUP. Failure of MTX treatment and the decision to intervene surgically were based on clinical signs of acute severe abdominal pain or haemodynamic imbalance and not on TVUS results. These conclusions should be viewed with respect to the specific protocol of the present study (i.e., inclusion criteria, single dose MTX, weekly TVUS) and the possibility that a different set of cases or a different protocol of TVUS monitoring would give different results cannot be ruled out.
Previous reports (Ory et al., 1986), and guidelines (American College of Obstetricians and Gynaecologists, 1999) have suggested that certain ultrasonographic features should contra-indicate treatment with MTX, e.g. the presence of free fluids or of an EUP mass >34 cm (at its greater dimension), as well as fetal heart rate (Ory et al., 1986
; American College of Obstetricians and Gynaecologists, 1999). According to our results, however, the size of the EUP mass was not different in the failed cases nor did it correlate with the level of hCG concentration. This is in accordance with a previous study (Lipscomb et al., 1999
) who reported that only the initial serum hCG concentration determines the success rate, whereas neither of the sonographic parameters has a significant value (Buster and Pisarska, 1999
; Lipscomb et al., 1999
). Although failure still occurs more often when fetal heartbeat is identified (Lipscomb et al., 1999
), such cases are usually accompanied with high hCG concentrations.
Furthermore, according to our results, the size of the ectopic mass increases in most cases during TVUS follow-up. This increase concurs with a previous report (Brown et al., 1991) in a small cohort. Thus, the decision for surgical intervention due to enlargement of the mass above certain limits is not justified.
Interestingly, we observed a few cases in which there was a change in the sonographic features of the tubal mass from primarily solid into a semi-solid mass containing more sonolucent areas. A possible explanation is the presence of blood clots and haematoma around the mass that cannot be easily separated from the main mass.
The present data support previous reports regarding the association between ectopic mass and hCG normalization (Brown et al., 1991; Lipscomb et al., 1999
). The resolution of the ectopic mass lagged far behind the hCG resolution in at least 12 cases. For example, the ectopic mass resolved in four women only 9 weeks after the hCG was <200 mIU/ml. This suggests that the residual mass is not an active trophoblastic tissue in most cases.
The main lessons that can be learned from the present study are that the initial size of tubal pregnancy is not related to the success of single-dose MTX treatment and that MTX treatment in tubal pregnancy is followed by an initial increase in the size of the ectopic mass.
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Notes |
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References |
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Submitted on February 4, 2002; resubmitted on May 20, 2002; accepted on June 27, 2002.