Ben W. J. Mol

The accuracy of hysterosalpingography in the diagnosis of tubal pathology: a meta-analysis

OBJECTIVEnTo assess the value of hysterosalpingography (HSG) in diagnosing tubal patency and peritubal adhesions using laparoscopy with chromopertubation as the gold standard.nnnDESIGNnMeta-analysis of 20 studies comparing HSG and laparoscopy for tubal patency and peritubal adhesions.nnnPATIENTSnFour thousand one hundred seventy-nine patients with infertility in 20 studies.nnnINTERVENTIONnHysterosalpingography and diagnostic laparoscopy as part of infertility workup.nnnMAIN OUTCOME MEASUREnTubal patency and peritubal adhesions.nnnRESULTSnFor tubal patency the reported sensitivity and specificity differed between studies. In a subset of studies that evaluated HSG and laparoscopy independently, a point estimate of 0.65 for sensitivity and 0.83 for specificity was calculated. For peritubal adhesions a summary receiver operating characteristic curve could be estimated.nnnCONCLUSIONSnAlthough HSG is of limited use for detecting tubal patency because of its low sensitivity, its high specificity makes it a useful test for ruling in tubal obstruction. For the evaluation of peritubal adhesions HSG is not reliable.

The performance of CA-125 measurement in the detection of endometriosis: a meta-analysis

OBJECTIVEnTo assess the diagnostic performance of serum CA-125 measurement in the detection of endometriosis.nnnDESIGNnMeta-analysis.nnnSETTING AND PATIENT(S)nTwenty-three studies comparing serum CA-125 levels and laparoscopically confirmed endometriosis.nnnINTERVENTION(S)nSerum CA-125 measurement and laparoscopy.nnnMAIN OUTCOME MEASURE(S)nSensitivity and specificity of serum CA-125 measurement in the diagnosis of endometriosis with laparoscopy as the reference standard.nnnRESULT(S)nThe estimated summary receiver operating characteristic curves showed that the performance of serum CA-125 measurement in the diagnosis of endometriosis grade I/IV is limited, whereas its performance in the diagnosis of endometriosis grade III/IV is better.nnnCONCLUSION(S)nDespite its limited diagnostic performance, we believe that the routine use of serum CA-125 measurement in patients with infertility might be justified. In contrast to laparoscopy, serum CA-125 measurement is an inexpensive test that is not a burden for the patient. It could identify a subgroup of patients who are more likely to benefit from early laparoscopy. Studies reporting on the mutual dependence between serum CA-125 measurement and data from the history and physical examination are needed.

The accuracy of serum chlamydial antibodies in the diagnosis of tubal pathology: a meta-analysis

OBJECTIVEnTo assess the discriminative capacity of Chlamydia antibody titers in the diagnosis of tubed pathology in subfertile patients.nnnDESIGNnMeta-analysis of studies comparing Chlamydia antibody titers and laparoscopy for tubal patency and peritubal adhesions.nnnPATIENTSnA total of 2,729 patients with subfertility in 23 studies.nnnINTERVENTION(S)nChlamydia antibody titer and laparoscopy as part of subfertility work-up.nnnMAIN OUTCOME MEASUREnSensitivity and specificity of Chlamydia antibody titers in the diagnosis of tubal pathology using laparoscopy with chromopertubation as the reference standard.nnnRESULT(S)nThe discriminative capacity of Chlamydia antibody titers depended on the type of assay that was used. Summary receiver operating characteristic (ROC) curves of studies using ELISA or (micro)immunofluorescence revealed a better discrimination than the summary ROC-curve of studies using immunoperoxidase assay.nnnCONCLUSION(S)nThe discriminative capacity of Chlamydia antibody titers by means of ELISA, microimmunofluorescence, or immunofluorescence in the diagnosis of any tubal pathology is comparable to that of hysterosalpingography (HSG) in the diagnosis of tubal occlusion. Chlamydia antibody testing involves little burden but provides no details on the anatomy of uterus and tubes. Whether or not Chlamydia antibody testing can replace HSG depends on the perspective taken in the diagnostic work-up of subfertility.

Serum human chorionic gonadotropin measurement in the diagnosis of ectopic pregnancy when transvaginal sonography is inconclusive

OBJECTIVEnTo assess the accuracy of initial and repeated serum hCG measurements in the diagnosis of ectopic pregnancy (EP) in patients in whom transvaginal sonography is inconclusive and to evaluate whether patient characteristics influence the accuracy of serum hCG measurements.nnnDESIGNnProspective study.nnnSETTINGnTwo large teaching hospitals in Amsterdam, the Netherlands.nnnPATIENT(S)nThree hundred fifty-four consecutively seen pregnant patients with suspected EP and inconclusive transvaginal sonographic findings.nnnINTERVENTION(S)nSerum hCG measurements.nnnMAIN OUTCOME MEASURE(S)nThe performance of repeated serum hCG measurements in the diagnosis of EP was evaluated through the analysis of receiver operating characteristic curves.nnnRESULT(S)nInitial serum hCG measurements were more diagnostic in conjunction with sonographic evidence of an ectopic mass or fluid in the pouch of Douglas than in the absence of sonographic abnormalities. On repeated measurement, the course of the serum hCG concentration provided more diagnostic information than did the absolute serum hCG concentration 2 and 4 days after the start of the diagnostic process.nnnCONCLUSION(S)nThe interpretation of serum hCG measurements should depend on additional findings at transvaginal sonography. A cutoff level of 1,500 IU/L is recommended for patients with an ectopic mass or fluid in the pouch of Douglas; in patients without these findings, the cutoff level should be at least 2,000 IU/L. Four days after the start of the diagnostic process, any rise in the serum hCG concentration makes the diagnosis of EP very likely.

Salpingotomy versus salpingectomy in women with tubal pregnancy (ESEP study): an open-label, multicentre, randomised controlled trial.

BACKGROUNDnTubal ectopic pregnancy can be surgically treated by salpingectomy, in which the affected Fallopian tube is removed, or salpingotomy, in which the tube is preserved. Despite potentially increased risks of persistent trophoblast and repeat ectopic pregnancy, salpingotomy is often preferred over salpingectomy because the preservation of both tubes is assumed to offer favourable fertility prospects, although little evidence exists to support this assumption. We aimed to assess whether salpingotomy would improve rates of ongoing pregnancy by natural conception compared with salpingectomy.nnnMETHODSnIn this open-label, multicentre, international, randomised controlled trial, women aged 18 years and older with a laparoscopically confirmed tubal pregnancy and a healthy contralateral tube were randomly assigned via a central internet-based randomisation program to receive salpingotomy or salpingectomy. The primary outcome was ongoing pregnancy by natural conception. Differences in cumulative ongoing pregnancy rates were expressed as a fecundity rate ratio with 95% CI, calculated by Cox proportional-hazards analysis with a time horizon of 36 months. Secondary outcomes were persistent trophoblast and repeat ectopic pregnancy (expressed as relative risks [RRs] with 95% CIs) and ongoing pregnancy after ovulation induction, intrauterine insemination, or IVF. The researchers who collected data for fertility outcomes were masked to the assigned intervention, but patients and the investigators who analysed the data were not. All endpoints were analysed by intention to treat. We also did a (non-prespecified) meta-analysis that included the findings from the present trial. This trial is registered, number ISRCTN37002267.nnnFINDINGSn446 women were randomly assigned between Sept 24, 2004, and Nov 29, 2011, with 215 allocated to salpingotomy and 231 to salpingectomy. Follow-up was discontinued on Feb 1, 2013. The cumulative ongoing pregnancy rate was 60·7% after salpingotomy and 56·2% after salpingectomy (fecundity rate ratio 1·06, 95% CI 0·81-1·38; log-rank p=0·678). Persistent trophoblast occurred more frequently in the salpingotomy group than in the salpingectomy group (14 [7%] vs 1 [<1%]; RR 15·0, 2·0-113·4). Repeat ectopic pregnancy occurred in 18 women (8%) in the salpingotomy group and 12 (5%) women in the salpingectomy group (RR 1·6, 0·8-3·3). The number of ongoing pregnancies after ovulation induction, intrauterine insemination, or IVF did not differ significantly between the groups. 43 (20%) women in the salpingotomy group were converted to salpingectomy during the initial surgery because of persistent tubal bleeding. Our meta-analysis, which included our own results and those of one other study, substantiated the results of the trial.nnnINTERPRETATIONnIn women with a tubal pregnancy and a healthy contralateral tube, salpingotomy does not significantly improve fertility prospects compared with salpingectomy.nnnFUNDINGnNetherlands Organisation for Health Research and Development (ZonMW), Region Västra Götaland Health & Medical Care Committee.

Harmonising evidence-based medicine teaching : a study of the outcomes of e-learning in five European countries

BackgroundWe developed and evaluated the outcomes of an e-learning course for evidence based medicine (EBM) training in postgraduate medical education in different languages and settings across five European countries.MethodsWe measured changes in knowledge and attitudes with well-developed assessment tools before and after administration of the course. The course consisted of five e-learning modules covering acquisition (formulating a question and search of the literature), appraisal, application and implementation of findings from systematic reviews of therapeutic interventions, each with interactive audio-visual learning materials of 15 to 20 minutes duration. The modules were prepared in English, Spanish, German and Hungarian. The course was delivered to 101 students from different specialties in Germany (psychiatrists), Hungary (mixture of specialties), Spain (general medical practitioners), Switzerland (obstetricians-gynaecologists) and the UK (obstetricians-gynaecologists). We analysed changes in scores across modules and countries.ResultsOn average across all countries, knowledge scores significantly improved from pre- to post-course for all five modules (p < 0.001). The improvements in scores were on average 1.87 points (14% of total score) for module 1, 1.81 points (26% of total score) for module 2, 1.9 points (11% of total score) for module 3, 1.9 points (12% of total score) for module 4 and 1.14 points (14% of total score) for module 5. In the country specific analysis, knowledge gain was not significant for module 4 in Spain, Switzerland and the UK, for module 3 in Spain and Switzerland and for module 2 in Spain. Compared to pre-course assessment, after completing the course participants felt more confident that they can assess research evidence and that the healthcare system in their country should have its own programme of research about clinical effectiveness.ConclusionE-learning in EBM can be harmonised for effective teaching and learning in different languages, educational settings and clinical specialties, paving the way for development of an international e-EBM course.

Effect of study design on the association between nuchal translucency measurement and Down syndrome

OBJECTIVEnTo evaluate the effect of verification bias on the accuracy of first-trimester nuchal translucency measurement for Down syndrome detection.nnnMETHODSnWe used MEDLINE and EMBASE to identify all papers relating the results of nuchal translucency measurement to fetal karyotype. The detected studies were scored for verification bias. Fifteen studies without and ten with verification bias were included.nnnRESULTSnSensitivity and specificity were calculated for each study. For studies with verification bias, adjusted estimates of the sensitivity were calculated assuming a fetal loss rate for Down syndrome pregnancies of 48%. The sample size weighted sensitivity was 55% in studies without and 77% in those with verification bias, for specificities of 96% and 97%, respectively. After adjustment for verification bias, the sample size weighted sensitivity changed from 77% to 63%.nnnCONCLUSIONnStudies with verification bias reported higher sensitivities, but also slightly higher specificities of nuchal translucency measurement than studies without verification bias. The difference in sensitivity is greater than could be explained by verification bias. We postulate that the experience of the sonographist might be an explanation for the differences.

Effectiveness of an e-learning course in evidence-based medicine for foundation (internship) training

Summary Aim To evaluate the educational effectiveness of a clinically integrated e-learning course for teaching basic evidence-based medicine (EBM) among postgraduate medical trainees compared to a traditional lecture-based course of equivalent content. Methods We conducted a cluster randomized controlled trial to compare a clinically integrated e-learning EBM course (intervention) to a lecture-based course (control) among postgraduate trainees at foundation or internship level in seven teaching hospitals in the UK West Midlands region. Knowledge gain among participants was measured with a validated instrument using multiple choice questions. Change in knowledge was compared between groups taking into account the cluster design and adjusted for covariates at baseline using generalized estimating equations (GEE) model. Results There were seven clusters involving teaching of 237 trainees (122 in the intervention and 115 in the control group). The total number of postgraduate trainees who completed the course was 88 in the intervention group and 72 in the control group. After adjusting for baseline knowledge, there was no difference in the amount of improvement in knowledge of EBM between the two groups. The adjusted post course difference between the intervention group and the control group was only 0.1 scoring points (95% CI −1.2–1.4). Conclusion An e-learning course in EBM was as effective in improving knowledge as a standard lecture-based course. The benefits of an e-learning approach need to be considered when planning EBM curricula as it allows standardization of teaching materials and is a potential cost-effective alternative to standard lecture-based teaching.

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

INTRODUCTIONnHysterosalpingo-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.nnnMETHODS AND PATIENTSnOne-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.nnnRESULTSnWhen 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.nnnCONCLUSIONnThere 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.

The effectiveness of a clinically integrated e-learning course in evidence-based medicine: A cluster randomised controlled trial

BackgroundTo evaluate the educational effects of a clinically integrated e-learning course for teaching basic evidence-based medicine (EBM) among postgraduates compared to a traditional lecture-based course of equivalent content.MethodsWe conducted a cluster randomised controlled trial in the Netherlands and the UK involving postgraduate trainees in six obstetrics and gynaecology departments. Outcomes (knowledge gain and change in attitude towards EBM) were compared between the clinically integrated e-learning course (intervention) and the traditional lecture based course (control). We measured change from pre- to post-intervention scores using a validated questionnaire assessing knowledge (primary outcome) and attitudes (secondary outcome).ResultsThere were six clusters involving teaching of 61 postgraduate trainees (28 in the intervention and 33 in the control group). The intervention group achieved slightly higher scores for knowledge gain compared to the control, but these results were not statistically significant (difference in knowledge gain: 3.5 points, 95% CI -2.7 to 9.8, p = 0.27). The attitudinal changes were similar for both groups.ConclusionA clinically integrated e-learning course was at least as effective as a traditional lecture based course and was well accepted. Being less costly than traditional teaching and allowing for more independent learning through materials that can be easily updated, there is a place for incorporating e-learning into postgraduate EBM curricula that offer on-the-job training for just-in-time learning.Trial registrationTrial registration number: ACTRN12609000022268.