Methotrexate or expectant management in women with an ectopic pregnancy or pregnancy of unknown location and low serum hCG concentrations? A randomized comparison.

STUDY QUESTION: What is the treatment success rate of systemic methotrexate (MTX) compared with expectant management in women with an ectopic pregnancy or a pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations? SUMMARY ANSWER: In women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations, expectant management is an alternative to medical treatment with single-dose systemic MTX. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: MTX is often used in asymptomatic women with an ectopic pregnancy or a PUL with low and plateauing serum hCG concentrations. These pregnancies may be self-limiting and watchful waiting is suggested as an alternative, but evidence from RCTs is lacking. The results of this RCT show that expectant management is an alternative to treatment with systemic MTX in a single-dose regimen in these women. STUDY DESIGN, SIZE, DURATION: A multicentre RCT women were assigned to systemic MTX (single dose) treatment or expectant management, using a web-based randomization program, block randomization with stratification for hospital and serum hCG concentration (<1000 versus 1000-2000 IU/l). The primary outcome measure was an uneventful decline of serum hCG to an undetectable level (<2 IU/l) by the initial intervention strategy. Secondary outcome measures included additional treatment, side effects and serum hCG clearance time. PARTICIPANTS, SETTING, METHODS: From April 2007 to January 2012, we performed a multicentre study in The Netherlands. All haemodynamically stable women >18 years old with both an ectopic pregnancy visible on transvaginal sonography and a plateauing serum hCG concentration <1500 IU/l or with a PUL and a plateauing serum hCG concentration <2000 IU/l were eligible for the trial. MAIN RESULTS: We included 73 women of whom 41 were allocated to single-dose MTX and 32 to expectant management. There was no difference in primary treatment success rate of single-dose MTX versus expectant management, 31/41 (76%) and 19/32 (59%), respectively [relative risk (RR) 1.3 95% confidence interval (CI) 0.9-1.8]. In nine women (22%), additional MTX injections were needed, compared with nine women (28%) in whom systemic MTX was administered after initial expectant management (RR 0.8; 95% CI 0.4-1.7). One woman (2%) from the MTX group underwent surgery compared with four women (13%) in the expectant management group (RR 0.2; 95% CI 0.02-1.7), all after experiencing abdominal pain within the first week of follow-up. In the MTX group, nine women reported side effects versus none in the expectant management group. No serious adverse events were reported. Single-dose systemic MTX does not have a larger treatment effect compared with expectant management in women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations. WIDER IMPLICATIONS OF THE FINDINGS: Sixty percent of women after expectant management had an uneventful clinical course with steadily declining serum hCG levels without any intervention, which means that MTX, a potentially harmful drug, can be withheld in these women. BIAS, LIMITATION AND GENERALISABILITY: A limitation of this RCT is that it was an open (not placebo controlled) trial. Nevertheless, introduction of bias was probably limited by the strict criteria to be fulfilled for treatment with MTX. STUDY FUNDING: This trial is supported by a grant of the Netherlands Organization for Health Research and Development (ZonMw Clinical fellow grant 90700154). TRIAL REGISTRATION: ISRCTN 48210491.

Guideline adherence in ectopic pregnancy management.

BACKGROUND: Evidence-based guidelines have been issued for ectopic pregnancy (EP), covering both diagnostic and therapeutic management. In general, guidelines aim to reduce practice variation and to improve quality of care. To assess the guideline adherence in the management of EP, we developed guideline-based quality indicators and measured patient care in various hospitals. METHODS: A panel of experts and clinicians developed quality indicators based on recommendations from the Dutch guideline on EP management, using the systematic RAND-modified Delphi method. With these indicators, patient care was assessed in six Dutch hospitals between January 2003 and December 2005. For each quality indicator, a ratio for guideline adherence was calculated. Overall adherence was reported, as well as adherence per hospital type, i.e. academic, teaching and non-teaching hospitals. RESULTS: Out of 30 guideline-based recommendations, 12 quality indicators were selected covering procedural, structural and outcome aspects of care. For 317 women surgically treated for EP, these aspects were assessed. Overall adherence to the guideline was 75%. The highest adherence (98%) was observed for performing transvaginal sonography during the diagnostic workup. The lowest adherence (21%) was observed for performing salpingotomy in case of contra-lateral tubal pathology. Wide variance in adherence (0-100%) existed between academic, teaching and non-teaching hospitals. CONCLUSIONS: The overall guideline adherence was reasonable, with ample room for improvement in various aspects of care. Further research should focus on the barriers for guideline dissemination and adherence, to further improve the management of EP.

Can hysterosalpingocontrast-sonography replace hysterosalpingography in the assessment of tubal subfertility?

INTRODUCTION: Hysterosalpingo-contrastsonography (HyCoSy) is a new method for assessing tubal patency using transvaginal ultrasound. It is thought to have several advantages over conventional hysterosalpingography (HSG). We prospectively evaluated the performance of HyCoSy and HSG in the diagnosis of tubal pathology. METHODS AND PATIENTS: One-hundred consecutive subfertile women underwent both HyCoSy and HSG in randomised order. Results of both tests were related to findings at laparoscopy with dye, which was used as the reference test. Each woman was asked to score the pain exsperienced at both procedures on a visual analogue scale. RESULTS: When laparoscopy with dye was used as reference test, the likelihood ratios of HyCoSy were slightly inferior to those obtained for HSG. Since the performance of HyCoSy was dependent on experience, the results were recalculated omitting the 50 initial procedures from the analysis. In that calculation, results of HyCoSy and HSG were comparable. There were no differences in pain experienced during the procedure, as there appeared also to be no differences in patient preferences. CONCLUSION: There appear to be no strong arguments either to replace HSG by HyCoSy, or to reject the use of HyCoSy. Both procedures can be used in the evaluation of tubal pathology.