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Background: Thin endometrium on ultrasound in the course of ovarian hyperstimulation has been thought to be associated with poor success rates after IVF, even in the absence of prior intrauterine surgery or infection. To assess the clinical significance of endometrial thickness (EMT) for IVF outcome, we performed a systematic review and meta-analysis., Methods: The electronic databases Pubmed, Cochrane and Embase were searched up to October 2013 for articles that studied the association between EMT and IVF outcome. The articles had to be written in the English or Dutch language. Studies were included if two-by-two tables for EMT and pregnancy rates could be constructed. Study quality was scored using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Summary receiver operating characteristic (sROC) curves were estimated to assess the accuracy of EMT in the prediction of pregnancy. In addition, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a Mantel-Haenszel random effect model expressing the association between EMT and pregnancy chances. Meta-regression was performed to determine if female age and number of oocytes at retrieval interacted in the estimated effect of EMT on IVF outcome., Results: A total of 1170 studies was retrieved by the search. The overall quality of the 22 studies included in the review and meta-analysis was moderate. The estimated sROC curve indicated a virtually absent discriminatory capacity of EMT in the prediction of pregnancy. A thin endometrium (≤ 7 mm) was observed in only 2.4% of the reported cases (260/10 724). In these cases a trend towards lower ongoing pregnancy and live birth rates for women with EMT ≤ 7 mm was observed [OR 0.38 (95% CI 0.09-1.5)]. The probability of clinical pregnancy for an EMT ≤ 7 mm was significantly lower compared with cases with EMT > 7 mm [23.3% versus 48.1%, OR 0.42 (95% CI 0.27-0.67)]. Positive and negative predictive values for the outcome of clinical pregnancy 77 and 48%, respectively. The relationship between the number of oocytes and female age on the one hand and pregnancy on the other hand was very weak making correction for these variables unfeasible., Conclusions: Current data indicate that EMT has a limited capacity to identify women who have a low chance to conceive after IVF. The frequently reported cut-off of 7 mm is related to a lower chance of pregnancy, but occurs infrequently. The use of EMT as a tool to decide on cycle cancellation, freezing of all embryos or refraining from further IVF treatment seems not to be justified based on the current meta-analysis. Further research is needed to investigate the real independent significance of EMT in IVF., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Approximately 15-20% of all clinically confirmed pregnancies end in a miscarriage. Intrauterine adhesions (IUAs) are a possible complication after miscarriage, but their prevalence and the contribution of possible risk factors have not been elucidated yet. In addition, the long-term reproductive outcome in relation to IUAs has to be elucidated., Methods: We systematically searched the literature for studies that prospectively assessed the prevalence and extent of IUAs in women who suffered a miscarriage. To be included, women diagnosed with a current miscarriage had to be systematically evaluated within 12 months by hysteroscopy after either spontaneous expulsion or medical or surgical treatment. Studies that included women with a history of recurrent miscarriage only or that evaluated the IUAs after elective abortion or beyond 12 months after the last miscarriage were not included. Subsequently, long-term reproductive outcomes after expectant (conservative), medical or surgical management were assessed in women with and without post-miscarriage IUAs., Results: We included 10 prospective studies reporting on 912 women with hysteroscopic evaluation within 12 months of miscarriage and 8 prospective studies, including 1770 women, reporting long-term reproductive outcome. IUAs were detected in 183 women, resulting in a pooled prevalence of 19.1% [95% confidence interval (CI): 12.8-27.5%]. The extent of IUAs was reported in 124 women (67.8%) and was mild, moderate and severe respectively in 58.1, 28.2 and 13.7% of cases. Relative to women with one miscarriage, women with two or three or more miscarriages showed an increased risk of IUAs by a pooled OR of 1.41 and 2.1, respectively. The number of dilatation and curettage (D&C) procedures seemed to be the main driver behind these associations. A total of 150 congenital and acquired intrauterine abnormalities were encountered in 675 women, resulting in a pooled prevalence of 22.4% (95% CI: 16.3-29.9%). Similar reproductive outcomes were reported subsequent to conservative, medical or surgical management for miscarriage, although the numbers of studies and of included women were limited. No studies reported long-term reproductive outcomes following post-miscarriage IUAs., Conclusions: IUAs are frequently encountered, in one in five women after miscarriage. In more than half of these, the severity and extent of the adhesions was mild, with unknown clinical relevance. Recurrent miscarriages and D&C procedures were identified as risk factors for adhesion formation. Congenital and acquired intrauterine abnormalities such as polyps or fibroids were frequently identified. There were no studies reporting on the link between IUAs and long-term reproductive outcome after miscarriage, while similar pregnancy outcomes were reported subsequent to conservative, medical or surgical management. Although this review does not allow strong clinical conclusions on treatment management, it signals an important clinical problem. Treatment strategies are proposed to minimize the number of D&C in an attempt to reduce IUAs.

BACKGROUND Although ovarian reserve tests (ORTs) are frequently used prior to IVF treatment for outcome prediction, their added predictive value is unclear. We assessed the added value of ORTs to patient characteristics in the prediction of IVF outcome. METHODS An individual patient data (IPD) meta-analysis from published studies was performed. Studies on FSH, anti-Müllerian hormone (AMH) or antral follicle count (AFC) in women undergoing IVF were identified and authors were contacted. Using random intercept logistic regression models, we estimated the added predictive value of ORTs for poor response and ongoing pregnancy after IVF, relative to patient characteristics. RESULTS We were able to collect 28 study databases, comprising 5705 women undergoing IVF. The area under the receiver-operating characteristic curve (AUC) for female age in predicting poor response was 0.61. AFC and AMH each significantly improved the model fit (P-value <0.001). Moreover, almost a similar accuracy was reached using AMH or AFC alone (AUC 0.78 and 0.76, respectively). Combining the two tests, however, did not improve prediction (AUC 0.80, P = 0.19) of poor response. In predicting ongoing pregnancy after IVF, age was the best single predictor (AUC 0.57), and none of the ORTs added any value. CONCLUSIONS This IPD meta-analysis demonstrates that AFC and AMH clearly add to age in predicting poor response. As single tests, AFC and AMH both fully cover the prediction of poor ovarian response. In contrast, none of the ORTs add any information to the limited capacity of female age to predict ongoing pregnancy after IVF. The clinical usefulness of ORTs prior to IVF will be limited to the prediction of ovarian response.

BACKGROUND The term 'pregnancy of unknown location' (PUL) refers to cases where a pregnancy test is positive but the pregnancy cannot be visualized by transvaginal sonography (TVS). Various strategies integrating TVS and serum hCG measures are used to follow-up until the location and/or viability of the pregnancy becomes clear; however, the optimal strategy to predict the outcome of pregnancy in women with PUL is unknown. Therefore, we performed a systematic review and meta-analysis to determine the diagnostic accuracy of the various serum hCG strategies in women with PUL. METHODS We searched Medline and EMBASE for articles which were published (in any language) from 1980 to January 2012 on strategies using serum hCG in women with PUL and reporting on the final outcome of pregnancy. RESULTS From 980 selected titles, 23 articles, all cohort studies, were included. There were 10 studies on a single serum hCG cut-off level, 4 on serum hCG ratio (hCG 48 h/hCG 0 h) and 6 on logistic regression modelling. Three other strategies were reported using serum hCG, serum progesterone and/or uterine curettage findings; each of these strategies comprised a single study. Comparative diagnostic studies have not been performed on the diagnostic value of serum hCG in women with PUL. Included studies showed substantial clinical heterogeneity in the definition of the outcome, and only data for the pregnancy outcome ectopic pregnancy (EP) were suitable for meta-analysis. The receiver operating characteristic curves showed that the serum hCG ratios and logistic regression models had a better performance as compared with an absolute single serum hCG level (as the curve was considerably closer to the diagonal, indicating no diagnostic value). CONCLUSIONS Overall the study was limited by the high clinical heterogeneity of the data but in women with PUL diagnostic strategies using serum hCG ratios, either alone or in logistic regression models, have the best diagnostic performance in the case of EP. Well defined prospective comparative studies using standardized diagnostics and clinical application plus agreed definitions of outcome are required to identify the best strategy to diagnose pregnancy outcome in women with PUL.

Background: The Chlamydia IgG antibody test (CAT) shows considerable variations in reported estimates of test accuracy, partly because of the use of different assays and cut-off values. The aim of this study was to reassess the accuracy of CAT in diagnosing tubal pathology by individual patient data (IPD) meta-analysis for three different CAT assays., Methods: We approached authors of primary studies that used micro-immunofluorescence tests (MIF), immunofluorescence tests (IF) or enzyme-linked immunosorbent assay tests (ELISA). Using the obtained IPD, we performed pooled receiver operator characteristics analysis and logistic regression analysis with a random effects model to compare the three assays. Tubal pathology was defined as either any tubal obstruction or bilateral tubal obstruction., Results: We acquired data of 14 primary studies containing data of 6191 women, of which data of 3453 women were available for analysis. The areas under the curve for ELISA, IF and MIF were 0.64, 0.65 and 0.75, respectively (P-value < 0.001) for any tubal pathology and 0.66, 0.66 and 0.77, respectively (P-value = 0.01) for bilateral tubal pathology., Conclusions: In Chlamydia antibody testing, MIF is superior in the assessment of tubal pathology. In the initial screen for tubal pathology MIF should therefore be the test of first choice.

Background: Conventional meta-analysis has estimated the sensitivity and specificity of hysterosalpingography (HSG) to be 65% and 83%. The impact of patient characteristics on the accuracy of HSG is unknown. The aim of this study was to assess by individual patient data meta-analysis whether the accuracy of HSG is associated with different patient characteristics., Methods: We approached authors of primary studies reporting on the accuracy of HSG using findings at laparoscopy as the reference. We assessed whether patient characteristics such as female age, duration of subfertility and a clinical history without risk factors for tubal pathology were associated with the accuracy of HSG, using a random intercept logistic regression model., Results: We acquired data of seven primary studies containing data of 4521 women. Pooled sensitivity and specificity of HSG were 53% and 87% for any tubal pathology and 46% and 95% for bilateral tubal pathology. In women without risk factors, the sensitivity of HSG was 38% for any tubal pathology, compared with 61% in women with risk factors (P = 0.005). For bilateral tubal pathology, these rates were 13% versus 47% (P = 0.01). For bilateral tubal pathology, the sensitivity of HSG decreased with age [factor 0.93 per year (P = 0.05)]. The specificity of HSG was very stable across all subgroups., Conclusions: The accuracy of HSG in detecting tubal pathology was similar in all subgroups, except for women without risk factors in whom sensitivity was lower, possibly due to false-positive results at laparoscopy. HSG is a useful tubal patency screening test for all infertile couples.

Background: Anti-Mullerian hormone (AMH) is a marker of ovarian reserve status and represents a good predictor of ovarian response to ovarian hyperstimulation. The aim of this study was to assess the accuracy of AMH and antral follicle count (AFC) as predictors of an excessive response in IVF/ICSI treatment., Methods: A systematic review and meta-analysis of the existing literature was performed. Studies were included if 2 × 2 tables for the outcome excessive response in IVF patients in relation to AMH/AFC could be constructed. Using a bivariate meta-analytic model, both summary point estimates for sensitivity and specificity were calculated, as well as summary ROC curves. Clinical value was analysed by calculating post-test probabilities of excessive response at optimal cut-off levels, as well as the corresponding abnormal test rates., Results: Nine studies reporting on AMH and five reporting on AFC were found. Summary estimates of sensitivity and specificity for AMH were 82 and 76%, respectively, and 82 and 80%, respectively, for AFC. Comparison of the summary estimates and ROC curves for AMH and AFC showed no statistical difference. Abnormal test rates for AMH and AFC amounted to ∼14 and 16%, respectively, at cut-off levels where test performance is optimal [likelihood ratio for a positive result (LR + ) > 8], with a post-test probability of ± 70%., Conclusions: Both AMH and AFC are accurate predictors of excessive response to ovarian hyperstimulation. Moreover, both tests appear to have clinical value. This opens ways to explore the potential of individualized FSH dose regimens based on ovarian reserve testing.