PMID- 22736326 OWN - NLM STAT- MEDLINE DCOM- 20130111 LR - 20220408 IS - 1460-2350 (Electronic) IS - 0268-1161 (Linking) VI - 27 IP - 9 DP - 2012 Sep TI - Evaluation of a panel of 28 biomarkers for the non-invasive diagnosis of endometriosis. PG - 2698-711 LID - 10.1093/humrep/des234 [doi] AB - BACKGROUND: At present, the only way to conclusively diagnose endometriosis is laparoscopic inspection, preferably with histological confirmation. This contributes to the delay in the diagnosis of endometriosis which is 6-11 years. So far non-invasive diagnostic approaches such as ultrasound (US), MRI or blood tests do not have sufficient diagnostic power. Our aim was to develop and validate a non-invasive diagnostic test with a high sensitivity (80% or more) for symptomatic endometriosis patients, without US evidence of endometriosis, since this is the group most in need of a non-invasive test. METHODS: A total of 28 inflammatory and non-inflammatory plasma biomarkers were measured in 353 EDTA plasma samples collected at surgery from 121 controls without endometriosis at laparoscopy and from 232 women with endometriosis (minimal-mild n = 148; moderate-severe n = 84), including 175 women without preoperative US evidence of endometriosis. Surgery was done during menstrual (n = 83), follicular (n = 135) and luteal (n = 135) phases of the menstrual cycle. For analysis, the data were randomly divided into an independent training (n = 235) and a test (n = 118) data set. Statistical analysis was done using univariate and multivariate (logistic regression and least squares support vector machines (LS-SVM) approaches in training- and test data set separately to validate our findings. RESULTS: In the training set, two models of four biomarkers (Model 1: annexin V, VEGF, CA-125 and glycodelin; Model 2: annexin V, VEGF, CA-125 and sICAM-1) analysed in plasma, obtained during the menstrual phase, could predict US-negative endometriosis with a high sensitivity (81-90%) and an acceptable specificity (68-81%). The same two models predicted US-negative endometriosis in the independent validation test set with a high sensitivity (82%) and an acceptable specificity (63-75%). CONCLUSIONS: In plasma samples obtained during menstruation, multivariate analysis of four biomarkers (annexin V, VEGF, CA-125 and sICAM-1/or glycodelin) enabled the diagnosis of endometriosis undetectable by US with a sensitivity of 81-90% and a specificity of 63-81% in independent training- and test data set. The next step is to apply these models for preoperative prediction of endometriosis in an independent set of patients with infertility and/or pain without US evidence of endometriosis, scheduled for laparoscopy. FAU - Vodolazkaia, A AU - Vodolazkaia A AD - Leuven University Fertility Centre, Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Leuven, Belgium. FAU - El-Aalamat, Y AU - El-Aalamat Y FAU - Popovic, D AU - Popovic D FAU - Mihalyi, A AU - Mihalyi A FAU - Bossuyt, X AU - Bossuyt X FAU - Kyama, C M AU - Kyama CM FAU - Fassbender, A AU - Fassbender A FAU - Bokor, A AU - Bokor A FAU - Schols, D AU - Schols D FAU - Huskens, D AU - Huskens D FAU - Meuleman, C AU - Meuleman C FAU - Peeraer, K AU - Peeraer K FAU - Tomassetti, C AU - Tomassetti C FAU - Gevaert, O AU - Gevaert O FAU - Waelkens, E AU - Waelkens E FAU - Kasran, A AU - Kasran A FAU - De Moor, B AU - De Moor B FAU - D'Hooghe, T M AU - D'Hooghe TM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120626 PL - England TA - Hum Reprod JT - Human reproduction (Oxford, England) JID - 8701199 RN - 0 (Biomarkers) RN - 9G34HU7RV0 (Edetic Acid) SB - IM MH - Adult MH - Biomarkers/*metabolism MH - Case-Control Studies MH - Edetic Acid/metabolism MH - Endometriosis/*blood/*diagnosis MH - Female MH - Humans MH - Inflammation MH - Laparoscopy MH - Least-Squares Analysis MH - Menstrual Cycle MH - Middle Aged MH - Models, Statistical MH - ROC Curve MH - Regression Analysis MH - Sensitivity and Specificity EDAT- 2012/06/28 06:00 MHDA- 2013/01/12 06:00 CRDT- 2012/06/28 06:00 PHST- 2012/06/28 06:00 [entrez] PHST- 2012/06/28 06:00 [pubmed] PHST- 2013/01/12 06:00 [medline] AID - des234 [pii] AID - 10.1093/humrep/des234 [doi] PST - ppublish SO - Hum Reprod. 2012 Sep;27(9):2698-711. doi: 10.1093/humrep/des234. Epub 2012 Jun 26.