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Meta-Analysis
. 2016 May 1;2016(5):CD012179.
doi: 10.1002/14651858.CD012179.

Blood biomarkers for the non-invasive diagnosis of endometriosis

Vicki Nisenblat  1 , Patrick M M Bossuyt, Rabia Shaikh, Cindy Farquhar, Vanessa Jordan, Carola S Scheffers, Ben Willem J Mol, Neil Johnson, M Louise Hull
Affiliations
Meta-Analysis

Blood biomarkers for the non-invasive diagnosis of endometriosis

Vicki Nisenblat et al. Cochrane Database Syst Rev. .

Abstract

Background: About 10% of reproductive-aged women suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive or minimally invasive tests available in clinical practice to accurately diagnose endometriosis. Although other reviews have assessed the ability of blood tests to diagnose endometriosis, this is the first review to use Cochrane methods, providing an update on the rapidly expanding literature in this field.

Objectives: To evaluate blood biomarkers as replacement tests for diagnostic surgery and as triage tests to inform decisions on surgery for endometriosis. Specific objectives include:1. To provide summary estimates of the diagnostic accuracy of blood biomarkers for the diagnosis of peritoneal, ovarian and deep infiltrating pelvic endometriosis, compared to surgical diagnosis as a reference standard.2. To assess the diagnostic utility of biomarkers that could differentiate ovarian endometrioma from other ovarian masses.

Search methods: We did not restrict the searches to particular study designs, language or publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to May 2015, as well as these databases to 20 April 2015: CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed.

Selection criteria: We considered published, peer-reviewed, randomised controlled or cross-sectional studies of any size, including prospectively collected samples from any population of reproductive-aged women suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of one or more blood biomarkers with the findings of surgical visualisation of endometriotic lesions.

Data collection and analysis: Two authors independently collected and performed a quality assessment of data from each study. For each diagnostic test, we classified the data as positive or negative for the surgical detection of endometriosis, and we calculated sensitivity and specificity estimates. We used the bivariate model to obtain pooled estimates of sensitivity and specificity whenever sufficient datasets were available. The predetermined criteria for a clinically useful blood test to replace diagnostic surgery were a sensitivity of 0.94 and a specificity of 0.79 to detect endometriosis. We set the criteria for triage tests at a sensitivity of ≥ 0.95 and a specificity of ≥ 0.50, which 'rules out' the diagnosis with high accuracy if there is a negative test result (SnOUT test), or a sensitivity of ≥ 0.50 and a specificity of ≥ 0.95, which 'rules in' the diagnosis with high accuracy if there is a positive result (SpIN test).

Main results: We included 141 studies that involved 15,141 participants and evaluated 122 blood biomarkers. All the studies were of poor methodological quality. Studies evaluated the blood biomarkers either in a specific phase of the menstrual cycle or irrespective of the cycle phase, and they tested for them in serum, plasma or whole blood. Included women were a selected population with a high frequency of endometriosis (10% to 85%), in which surgery was indicated for endometriosis, infertility work-up or ovarian mass. Seventy studies evaluated the diagnostic performance of 47 blood biomarkers for endometriosis (44 single-marker tests and 30 combined tests of two to six blood biomarkers). These were angiogenesis/growth factors, apoptosis markers, cell adhesion molecules, high-throughput markers, hormonal markers, immune system/inflammatory markers, oxidative stress markers, microRNAs, tumour markers and other proteins. Most of these biomarkers were assessed in small individual studies, often using different cut-off thresholds, and we could only perform meta-analyses on the data sets for anti-endometrial antibodies, interleukin-6 (IL-6), cancer antigen-19.9 (CA-19.9) and CA-125. Diagnostic estimates varied significantly between studies for each of these biomarkers, and CA-125 was the only marker with sufficient data to reliably assess sources of heterogeneity.The mean sensitivities and specificities of anti-endometrial antibodies (4 studies, 759 women) were 0.81 (95% confidence interval (CI) 0.76 to 0.87) and 0.75 (95% CI 0.46 to 1.00). For IL-6, with a cut-off value of > 1.90 to 2.00 pg/ml (3 studies, 309 women), sensitivity was 0.63 (95% CI 0.52 to 0.75) and specificity was 0.69 (95% CI 0.57 to 0.82). For CA-19.9, with a cut-off value of > 37.0 IU/ml (3 studies, 330 women), sensitivity was 0.36 (95% CI 0.26 to 0.45) and specificity was 0.87 (95% CI 0.75 to 0.99).Studies assessed CA-125 at different thresholds, demonstrating the following mean sensitivities and specificities: for cut-off > 10.0 to 14.7 U/ml: 0.70 (95% CI 0.63 to 0.77) and 0.64 (95% CI 0.47 to 0.82); for cut-off > 16.0 to 17.6 U/ml: 0.56 (95% CI 0.24, 0.88) and 0.91 (95% CI 0.75, 1.00); for cut-off > 20.0 U/ml: 0.67 (95% CI 0.50 to 0.85) and 0.69 (95% CI 0.58 to 0.80); for cut-off > 25.0 to 26.0 U/ml: 0.73 (95% CI 0.67 to 0.79) and 0.70 (95% CI 0.63 to 0.77); for cut-off > 30.0 to 33.0 U/ml: 0.62 (95% CI 0.45 to 0.79) and 0.76 (95% CI 0.53 to 1.00); and for cut-off > 35.0 to 36.0 U/ml: 0.40 (95% CI 0.32 to 0.49) and 0.91 (95% CI 0.88 to 0.94).We could not statistically evaluate other biomarkers meaningfully, including biomarkers that were assessed for their ability to differentiate endometrioma from other benign ovarian cysts.Eighty-two studies evaluated 97 biomarkers that did not differentiate women with endometriosis from disease-free controls. Of these, 22 biomarkers demonstrated conflicting results, with some studies showing differential expression and others no evidence of a difference between the endometriosis and control groups.

Authors' conclusions: Of the biomarkers that were subjected to meta-analysis, none consistently met the criteria for a replacement or triage diagnostic test. A subset of blood biomarkers could prove useful either for detecting pelvic endometriosis or for differentiating ovarian endometrioma from other benign ovarian masses, but there was insufficient evidence to draw meaningful conclusions. Overall, none of the biomarkers displayed enough accuracy to be used clinically outside a research setting. We also identified blood biomarkers that demonstrated no diagnostic value in endometriosis and recommend focusing research resources on evaluating other more clinically useful biomarkers.

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Conflict of interest statement

Vicki Nisenblat: none known. Patrick MM Bossuyt: none known. Rabia Shaikh: none known. Cindy Farquhar: Cindy Farquhar is a director/shareholder of a small day stay surgical unit and fertility/gynaecology clinic and undertakes private practice within those facilities. Vanessa Jordan: none known. Carola S Scheffers: none known. Ben Willem J Mol: none known. Neil Johnson: Professor Neil Johnson is involved in research funded by Abb‐Vie. He has received support to attend conferences from MSD, Merck‐Serono and Bayer. He has been on an advisory board for Vifor Pharma. M Louise Hull: Dr M. L. Hull obtained a grant of $10,000 to carry out a prevalence study of ultrasonographically diagnosed endometriosis in a fertility population.

Figures

1
1
Sequential approach to non‐invasive testing of endometriosis.
2
2
Flow of the studies identified in literature search for systematic review on imaging modalities for a non‐invasive diagnosis of endometriosis.
3
3
Risk of bias and applicability concerns graph: review authors' judgements about each domain presented as percentages across included studies
4
4
Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study
5
5
Summary ROC plot of Glycodelin for detection of endometriosis. Each point represents the pair of sensitivity and specificity for each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different cut‐off values. The bars correspond to 95% CIs of each individual evaluation. Two evaluations (> 9 ng/ml and > 18 ng/ml) were performed on overlapping populations. The data were not assessed by meta‐analysis.
6
6
Summary ROC plot of VEGF for detection of endometriosis. Each point represents the pair of sensitivity and specificity for each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different cut‐off values. The bars correspond to 95% CIs of each individual evaluation. The data were not assessed by meta‐analysis.
7
7
Summary ROC plot of proteome by SELDI‐TOF‐MS for detection of endometriosis. Each point represents the pair of sensitivity and specificity for each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different sets of proteins determined by molecular weight (MW) in daltons (Da). The bars correspond to 95% CIs of each individual evaluation. The data were not assessed by meta‐analysis.
8
8
Forest plot of anti‐endometrial Abs for detection of endometriosis. Plot shows study‐specific estimates of sensitivity and specificity (squares) with 95% CI (black line), country in which the study was conducted, menstrual cycle phase at which the test was performed and severity of the disease assessed by each study, reported as rASRM stage. The studies are ordered according to the study names. FN: false negative; FP: false positive; TN: true negative; TP: true positive.
9
9
Summary ROC plot of anti‐endometrial Abs, IgG for detection of endometriosis. Each point represents the pair of sensitivity and specificity from each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different sets of antibodies tested. The bars correspond to 95% CIs of each individual evaluation. The solid black circle represents the mean sensitivity and specificity, which is surrounded by a 95% confidence region (dotted line) and by 95% prediction region (dashed line). Meta‐analysis was performed for 4 studies (the data for Anti‐endometrial Abs (MW 26/34/42 kd) were not included, considering it as a separate test).
10
10
Summary ROC plot of TNF‐α for detection of endometriosis. Each point represents the pair of sensitivity and specificity for each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different cut‐off values. The bars correspond to 95% CIs of each individual evaluation. The data were not assessed by meta‐analysis.
11
11
Forest plot of IL‐6 (all the included evaluations) for detection of endometriosis. Plot shows estimates of sensitivity and specificity (squares) with 95% CI (black line) specific for each evaluation, country in which the study was conducted, menstrual cycle phase at which the test was performed and severity of the disease assessed by each study, reported as rASRM stage. The studies are ordered according to the study names. FN: false negative; FP: false positive; TN: true negative; TP: true positive.
12
12
Forest plot of IL‐6 with cut‐off values above 1.9‐2 pg/ml for detection of endometriosis. Plot shows estimates of sensitivity and specificity (squares) with 95% CI (black line) specific for each evaluation, country in which the study was conducted, menstrual cycle phase at which the test was performed and severity of the disease assessed by each study, reported as rASRM stage. The studies are ordered according to the study names. FN: false negative; FP: false positive; TN: true negative; TP: true positive.
13
13
Summary ROC plot of IL‐6 with cut‐off values ranging > 1.9‐2 pg/ml for detection of endometriosis. Each point represents the pair of sensitivity and specificity from each evaluation. The size of each point is proportional to the sample size the shape designates the tests with different sets of antibodies tested. The bars correspond to 95% CIs of each individual evaluation. The solid black circle represents the summary sensitivity and specificity.
14
14
Forest plot of direct comparisons of IL‐6 for detection of endometriosis performed between different cut‐off values in 2 separate studies. Plot shows the estimates of sensitivity and specificity (squares) with 95% CI (black line) specific for each evaluation, country in which the study was conducted, menstrual cycle phase at which the test was performed and severity of the disease assessed by each study, reported as rASRM stage. The studies are ordered according to the study names. FN: false negative; FP: false positive; TN: true negative; TP: true positive.
15
15
Summary ROC plot of IL‐8 for detection of endometriosis. Each point represents the pair of sensitivity and specificity from each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different cut‐off values. The bars correspond to 95% CIs of each individual evaluation. The data were not assessed by meta‐analysis.
16
16
Forest plot of hs‐CRP for detection of endometriosis. Plot shows the estimates of sensitivity and specificity (squares) with 95% CI (black line) specific for each evaluation, country in which the study was conducted, menstrual cycle phase at which the test was performed and severity of the disease assessed by each study, reported as rASRM stage. The studies are ordered according to the study names. FN: false negative; FP: false positive; TN: true negative; TP: true positive.
17
17
Summary ROC plot of hs‐CRP for detection of endometriosis. Each point represents the pair of sensitivity and specificity for each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different cut‐off values. The bars correspond to 95% CIs of each individual evaluation. Five evaluations (excluding 1 with a cut‐off > 438 μg/ml) were performed on overlapping populations. The data were not assessed by meta‐analysis.
18
18
Summary ROC plot of oxidative stress biomarkers for detection of endometriosis. Each point represents the pair of sensitivity and specificity from each evaluation. The size of each point is proportional to the sample size and the shape designates different biomarkers from this group, each assessed in a single study. The bars correspond to 95% CIs of each individual evaluation. The data were not assessed by meta‐analysis.
19
19
Summary ROC plot of microRNAs for detection of endometriosis. Each point represents the pair of sensitivity and specificity from each evaluation. The size of each point is proportional to the sample size and the shape designates different biomarkers from this group, each assessed in a single study. The bars correspond to 95% CIs of each individual evaluation. The data were not assessed by meta‐analysis.
20
20
Summary ROC plot of CA‐19.9 with a cut‐off value > 37 U/ml for detection of endometriosis. Each point represents the pair of sensitivity and specificity from each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different sets of antibodies tested. The bars correspond to 95% CIs of each individual evaluation. The solid black circle represents the summary sensitivity and specificity.
21
21
Forest plot of CA‐19.9 (all the evaluations) for detection of endometriosis. Plot shows estimates of sensitivity and specificity (squares) with 95% CI (black line) specific for each evaluation, country in which the study was conducted, menstrual cycle phase at which the test was performed and severity of the disease assessed by each study, reported as rASRM stage. The studies are ordered according to the study names. FN: false negative; FP: false positive; TN: true negative; TP: true positive.
22
22
Forest plot of CA‐125 (all the included evaluations) for detection of endometriosis. Plot shows the estimates of sensitivity and specificity (squares) with 95% CI (black line) specific for each evaluation, country in which the study was conducted, menstrual cycle phase at which the test was performed and severity of the disease assessed by each study, reported as rASRM stage. The studies are ordered according to the study names. FN: false negative; FP: false positive; TN: true negative; TP: true positive.
23
23
Summary ROC plot of CA‐125 with cut‐off values ranging > 10‐14.7 U/ml for detection of endometriosis. Each point represents the pair of sensitivity and specificity from each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different cut‐off values. The solid black circle represents the mean sensitivity and specificity, which is surrounded by a 95% confidence region (dotted line) and by 95% prediction region (dashed line). Meta‐analysis was performed for 5 studies (the data for 2 evaluations (CA‐125 > 11.5 U/ml and CA‐125 > 13.5 U/ml were not included as overlapping populations with already included study).
24
24
Summary ROC plot of CA‐125 with cut‐off values ranging > 16‐17.6 U/ml for detection of endometriosis. Each point represents the pair of sensitivity and specificity from each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different cut‐off values. The solid black circle represents the mean sensitivity and specificity, which is surrounded by a 95% confidence region (dotted line) ad by 95% prediction region (dashed line).
25
25
Summary ROC plot of CA‐125 with cut‐off values > 20 U/ml for detection of endometriosis. Each point represents the pair of sensitivity and specificity from each evaluation. The size of each point is proportional to the sample size. The solid black circle represents the mean sensitivity and specificity, which is surrounded by a 95% confidence region (dotted line) and by 95% prediction region (dashed line).
26
26
Summary ROC plot of CA‐125 with cut‐off values ranging > 25‐26 U/ml for detection of endometriosis. Each point represents the pair of sensitivity and specificity from each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different cut‐off values. The bars correspond to 95% CIs of each individual evaluation. The solid black circle represents the summary sensitivity and specificity.
27
27
Summary ROC plot of CA‐125 with cut‐off values ranging > 30‐33 U/ml for detection of endometriosis. Each point represents the pair of sensitivity and specificity from each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different cut‐off values. The solid black circle represents the mean sensitivity and specificity, which is surrounded by a 95% confidence region (dotted line) and by 95% prediction region (dashed line).
28
28
Summary ROC plot of CA‐125 with cut‐off values ranging > 35‐36 U/ml for detection of endometriosis. Each point represents the pair of sensitivity and specificity from each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different cut‐off values. The solid black circle represents the mean sensitivity and specificity, which is surrounded by a 95% confidence region (dotted line) and by 95% prediction region (dashed line).
29
29
Forest plot of direct comparisons of CA‐125 for detection of endometriosis performed between different cut‐off values in 8 separate studies. Plot shows the estimates of sensitivity and specificity (squares) with 95% CI (black line) specific for each evaluation, country in which the study was conducted, menstrual cycle phase at which the test was performed and severity of the disease assessed by each study, reported as rASRM stage. The studies are ordered according to the study names. FN: false negative; FP: false positive; TN: true negative; TP: true positive.
30
30
Forest plot of direct comparisons of CA‐125 for detection of endometriosis performed between different phases of menstrual cycle in 2 separate studies. Plot shows the estimates of sensitivity and specificity (squares) with 95% CI (black line) specific for each evaluation, country in which the study was conducted, menstrual cycle phase at which the test was performed and severity of the disease assessed by each study, reported as rASRM stage. The studies are ordered according to the study names. FN: false negative; FP: false positive; TN: true negative; TP: true positive.
31
31
Forest plot of the combined tests (all the included evaluations) for detection of endometriosis, which consist of the combinations of 2‐6 blood biomarkers. Plot shows the estimates of sensitivity and specificity (squares) with 95% CI (black line) specific for each evaluation, country in which the study was conducted, menstrual cycle phase at which the test was performed and severity of the disease assessed by each study, reported as rASRM stage. The studies are ordered according to the study names. FN: false negative; FP: false positive; TN: true negative; TP: true positive.
32
32
Forest plot of the combined tests for detection of endometriosis, which consist of the combinations of CA‐125 with other blood biomarkers. Plot shows the estimates of sensitivity and specificity (squares) with 95% CI (black line) specific for each evaluation, country in which the study was conducted, menstrual cycle phase at which the test was performed and severity of the disease assessed by each study, reported as rASRM stage. The studies are ordered according to the study names. FN: false negative; FP: false positive; TN: true negative; TP: true positive.
33
33
Forest plot of the most promising combined tests of blood biomarkers for detection of endometriosis. Plot shows the estimates of sensitivity and specificity (squares) with 95% CI (black line) specific for each evaluation, country in which the study was conducted, menstrual cycle phase at which the test was performed and severity of the disease assessed by each study, reported as rASRM stage. FN: false negative; FP: false positive; TN: true negative; TP: true positive.
34
34
Forest plot of the tests for detection of ovarian endometriosis performed through comparisons in women with endometriosis versus other benign ovarian cysts in 6 studies. Plot shows the estimates of sensitivity and specificity (squares) with 95% CI (black line) specific for each evaluation, country in which the study was conducted, menstrual cycle phase at which the test was performed and severity of the disease assessed by each study, reported as rASRM stage. The studies are ordered according to the study names. FN: false negative; FP: false positive; TN: true negative; TP: true positive.
35
35
Summary ROC plot of urocortin for detection of endometriosis. Each point represents the pair of sensitivity and specificity for each evaluation. The size of each point is proportional to the sample size and the shape designates the tests with different cut‐off values. The bars correspond to 95% CIs of each individual evaluation. Two evaluations (> 29 pg/ml and > 33 pg/ml) were performed in the same population. The data were not assessed by meta‐analysis.
1
1. Test
Glycodelin‐A (> 2.07 ng/ml).
2
2. Test
Glycodelin (> 9.0 ng/ml).
3
3. Test
Glycodelin (> 18 ng/ml).
4
4. Test
IGFBP‐3 (> 200 ng/ml).
5
5. Test
IGFBP‐3 (> 210 ng/ml).
6
6. Test
VEGF (> 1.5 pg/ml).
7
7. Test
VEGF (> 236 pg/ml).
8
8. Test
VEGF‐A (> 680 pg/ml).
9
9. Test
Urocortin (> 29 pg/ml), endometrioma.
10
10. Test
Urocortin (> 33 pg/ml), endometrioma.
11
11. Test
Urocortin (> 41.6 pg/ml), endometrioma.
12
12. Test
Survivin (cut‐off not reported).
13
13. Test
sICAM‐1 (< 243 ng/ml).
14
14. Test
sICAM‐1 (< 254.6 ng/ml).
15
15. Test
sICAM‐1 (> 241.46 µg/ml).
16
16. Test
LN‐1 (> 1110.0 pg/ml).
17
17. Test
Metabolome by ESI‐MS/MS (SMOH C16:1 + PCaa C36:2/ PCae C34:2) age‐/BMI‐adjusted.
18
18. Test
Proteome by SELDI‐TOF‐MS (3 peaks with the molecular weight of 3,956.00, 11,710.00 and 6,986.00 Da).
19
19. Test
Proteome by SELDI‐TOF MS (5 peaks with molecular weights of 4159.00, 5264.00, 5603.00, 9861.00 and 10,533.00 Da).
20
20. Test
Proteome by SELDI‐TOF MS (5 peaks with molecular weight of 9,926.31, 10,072.2, 6,753.04, 4,302.67, 9,328.49 Da).
21
21. Test
Proteome by SELDI‐TOF MS (5 peaks with molecular weight of 2,831.02, 7,554.66, 4,241.29, 2,953.25, 9,927.73 Da).
22
22. Test
Proteome by SELDI‐TOF MS (5 peaks with molecular weight of 11,366.3, 5,712.69, 10,070.7, 3,017.68, 3,824.44 Da).
23
23. Test
Proteome by SELDI‐TOF‐MS (6 peaks with molecular weights of 1629.00 3047.00, 3526.00, 3774.00, 5046.00 and 5068.00 Da).
24
24. Test
Prolactin (> 14.8 ng/ml).
25
25. Test
Prolactin (> 20 ng/ml).
26
26. Test
Anti‐endometrial Abs, IgG.
27
27. Test
Anti‐endometrial Abs (MW 26/34/42 kd).
28
28. Test
Anti‐laminin auto Abs, IgG (> 1 U/ml).
29
29. Test
sCD23 (cut‐off not reported).
30
30. Test
MCP‐1 (> 100 pg/ml).
31
31. Test
Copeptin (> 251.18 pg/ml).
32
32. Test
hs‐CRP (> 0.61 mg/l).
33
33. Test
hs‐CRP (> 0.62 mg/l).
34
34. Test
hs‐CRP (> 0.70 mg/l).
35
35. Test
hs‐CRP (> 0.73 mg/l).
36
36. Test
hs‐CRP (> 438 μg/ml).
37
37. Test
hs‐CRP (cut‐off not reported).
38
38. Test
IFN‐γ (< 76 pg/ml).
39
39. Test
MIF (> 0.57 ng/ml).
40
40. Test
TNF‐α (> 12.45 pg/ml).
41
41. Test
TNF‐α (< 45.6 pg/ml).
42
42. Test
TNF‐α (cut‐off not reported).
43
43. Test
Neutrophils (> 4058/ml).
44
44. Test
NLR (> 2.19).
45
45. Test
WBC (> 6400/ml).
46
46. Test
IL‐1β (< 0.9 pg/ml).
47
47. Test
IL‐4 (≥ 3 pg/ml).
48
48. Test
IL‐6 (> 1.03 pg/ml).
49
49. Test
IL‐6 (> 1.9 pg/ml).
50
50. Test
IL‐6 (> 2 pg/ml).
51
51. Test
IL‐6 (> 2.6 pg/ml).
52
52. Test
IL‐6 (> 4 pg/ml).
53
53. Test
IL‐6 (> 7.5 pg/ml).
54
54. Test
IL‐6 (< 10 pg/ml).
55
55. Test
IL‐6 (> 12.2 pg/ml).
56
56. Test
IL‐6 (> 15.4 pg/ml).
57
57. Test
IL‐6 (> 25.75 pg/ml).
58
58. Test
IL‐6 (cut‐off not reported).
59
59. Test
IL‐8 (> 24 pg/ml).
60
60. Test
IL‐8 (≥ 25 pg/ml), endometrioma.
61
61. Test
IL‐8 (cut‐off not reported).
62
62. Test
Follistatin (> 1433 pg/ml), endometrioma.
63
63. Test
STX‐5 (> 55 ng/ml).
64
64. Test
Carbonyls (< 14.9 μM).
65
65. Test
PON‐1 (< 141.5 U/l).
66
66. Test
Thiols (< 396.44 μM).
67
67. Test
miR‐9* (cut‐off not reported).
68
68. Test
miR‐17‐5 (< 0.9057).
69
69. Test
miR‐20a (< 0.6879).
70
70. Test
miR‐22 (< 0.5647).
71
71. Test
miR‐122 (cut‐off not reported).
72
72. Test
miR‐141* (cut‐off not reported).
73
73. Test
miR‐145* (cut‐off not reported).
74
74. Test
miR‐199a (cut‐off not reported).
75
75. Test
miR‐532‐3p (cut‐off not reported).
76
76. Test
Ca‐15.3 (> 15 IU/ml).
77
77. Test
Ca‐15.3 (> 30 IU/ml).
78
78. Test
CA‐19.9 (> 7.5 IU/ml).
79
79. Test
CA‐19.9 (> 9.5 IU/ml).
80
80. Test
CA‐19.9 (> 10.67 IU/ml).
81
81. Test
CA‐19.9 (≥ 12 U/ml), endometrioma.
82
82. Test
CA‐19.9 (> 37 IU/ml).
83
83. Test
CA‐19.9 (cut‐off not reported).
84
84. Test
CA‐72 (TAG‐72) (> 4 U/ml).
85
85. Test
CA‐72 (TAG‐72) (> 6 U/ml).
86
86. Test
CA‐125 (> 10 IU/ml).
87
87. Test
CA‐125 (> 11 U/ml).
88
88. Test
CA‐125 (> 11.5 U/ml).
89
89. Test
CA‐125 (> 12.5 U/ml).
90
90. Test
CA‐125 (> 12.8 U/ml).
91
91. Test
CA‐125 (> 13.5 U/ml).
92
92. Test
CA‐125 (> 14.7 IU/ml).
93
93. Test
CA‐125 (> 16 U/ml).
94
94. Test
CA‐125 (> 17.6 IU/ml).
95
95. Test
CA‐125 (> 20 IU/ml).
96
96. Test
CA‐125 (> 20 U/ml), endometrioma.
97
97. Test
CA‐125 (> 25 U/ml), endometrioma.
98
98. Test
CA‐125 (> 26 IU/ml).
99
99. Test
CA‐125 (> 30 U/ml).
100
100. Test
CA‐125 (> 30 U/ml), endometrioma.
101
101. Test
CA‐125 (> 33 U/ml).
102
102. Test
CA‐125 (> 35 U/ml).
103
103. Test
CA‐125 (> 35 U/ml), endometrioma.
104
104. Test
CA‐125 (> 36 U/l) endometrioma.
105
105. Test
CA‐125 (> 42 U/l), endometrioma.
106
106. Test
CA‐125 (> 43 U/ml).
107
107. Test
CA‐125 (cut‐off not reported).
108
108. Test
CA‐125 (cut‐off not reported).
109
109. Test
CA‐125 (cut‐off not reported).
110
110. Test
CA‐125 (cut‐off not reported).
111
111. Test
Combined test (CA‐125 ≥ 25 U/ml +/or CA‐19.9 ≥ 12 U/ml), endometrioma.
112
112. Test
Combined test (CA‐125 ≥ 25 U/ml + Ca‐19.9 ≥ 12 U/ml), endometrioma.
113
113. Test
Combined test (CA‐125 > 19.8 U/l + Prolactin > 14.8 ng/ml).
114
114. Test
Combined test (CA‐125 > 35 U/l + Prolactin > 20 ng/ml).
115
115. Test
Combined test (CA‐125 > 17.6 IU/ml + VEGF > 236 pg/ml).
116
116. Test
Combined test (CA‐125 > 20 U/l + Anti‐endometrial Abs > 0.3 A‐value).
117
117. Test
Combined test (CA‐125 x NLR; (> 43.1).
118
118. Test
Combined test (CA‐125 > 30 U/ml +/or IL‐8 ≥ 25 pg/ml), endometrioma.
119
119. Test
Combined test (CA‐125 + IL‐8) (cut‐off not reported).
120
120. Test
Combined test (IL‐6 > 12.2 pg/ml + TNF‐α > 12.45 pg/ml).
121
121. Test
Combined test (IL‐6 > 12.2 pg/ml + CRP > 438 μg/ml).
122
122. Test
Combined test (TNF‐α > 12.45 pg/ml + CRP > 438 μg/ml).
123
123. Test
Combined test (miR‐199a + miR‐122) (cut‐off not reported).
124
124. Test
Combined test (miR‐199a + miR‐542‐3p) (cut‐off not reported).
125
125. Test
Combined test (Ca‐125 + Ca 19‐9 + Survivin) (cut‐off not reported).
126
126. Test
Combined test (CA‐125 + STX‐5 + LN‐1) (cut‐off not reported).
127
127. Test
Combined test (CA‐125 > 35 IU/ml +/or CA‐19.9 > 37 IU/ml +/or IL‐6 > 2 pg/ml).
128
128. Test
Combined test (CA‐125 > 50 IU/mL +/ or CCR1 > 1.16 +/or MCP‐1 > 140 pg/ml).
129
129. Test
Combined test (Ca‐125 > 20 mIU/ml + MCP‐1 > 152.74 pg/ml + Leptin > 3.14 ng/ml).
130
130. Test
Combined test CA‐125 + IL‐8 + TNF‐α) (cut‐off not reported).
131
131. Test
Combined test (IL‐6 > 12.2 pg/ml + TNF‐α > 12.45 pg/ml + CRP > 438 μg/ml).
132
132. Test
Combined test (CA‐125 + VEGF + annexin V + glycodelin] ‐ MLR (cut‐off not reported).
133
133. Test
Combined test (CA‐125 + VEGF + annexin V + glycodelin] ‐ LS‐SVM (cut‐off not reported).
134
134. Test
Combined test (CA‐125 + VEGF + annexin V + sICAM‐1) ‐ MLR or LS‐SVM (cut‐off not reported).
135
135. Test
Combined test (CA‐125 > 20 mIU/ml + MCP‐1 > 53.5 pg/ml + Leptin > 29.1 ng/ml + MIF > 14.7 ng/ml).
136
136. Test
Combined test (miR‐199a + miR‐122 + miR‐145* + miR‐542‐3p) (cut‐off not reported).
137
137. Test
Combined test (CA‐125 + CA‐19.9 + IL‐6 + IL‐8 + TNF‐α + hs‐CRP) (cut‐off not reported).
138
138. Test
Combined test (CA‐125 + CA‐19.9 + IL‐6 + IL‐8 + TNF‐α + hs‐CRP) (cut‐off not reported).
139
139. Test
Combined test (CA‐125 + CA‐19.9 + IL‐6 + IL‐8 + TNF‐α + hs‐CRP) (cut‐off not reported).
140
140. Test
Combined test (CA‐125 + CA‐19.9 + IL‐6 + IL‐8 + TNF‐α + hs‐CRP) (cut‐off not reported).
141
141. Test
CA‐125 (> 20 U/ml), Bilibio 2014.
142
142. Test
CA‐125 (> 35 U/ml), Bilibio 2014.
143
143. Test
CA‐125 (> 16 U/ml), Ferreira 1994.
144
144. Test
CA‐125 (> 35 U/ml), Ferreira 1994.
145
145. Test
CA‐125 (> 30 U/ml), Florio 2007.
146
146. Test
CA‐125 (> 36 U/ml), Florio 2007.
147
147. Test
CA‐125 (> 12.8 U/ml), Gagne 2003a.
148
148. Test
CA‐125 (> 35 U/ml), Gagne 2003a.
149
149. Test
CA‐125 (> 20 U/ml), Guerriero 1996b.
150
150. Test
CA‐125 (≥ 25 U/ml), Guerriero 1996b.
151
151. Test
CA‐125 (> 35 U/ml), Guerriero 1996b.
152
152. Test
CA‐125 (> 20 U/ml), Kitawaki 2005.
153
153. Test
CA‐125 (> 26 U/ml), Kitawaki 2005.
154
154. Test
CA‐125 (> 30 U/ml), Kitawaki 2005.
155
155. Test
CA‐125 (> 35 U/ml), Kitawaki 2005.
156
156. Test
CA‐125 (> 10 U/ml), Rosa E Silva 2007.
157
157. Test
CA‐125 (> 20 U/ml), Rosa E Silva 2007.
158
158. Test
CA‐125 (> 20 U/ml), Yang 1994.
159
159. Test
CA‐125 (> 35 U/ml), Yang 1994.
160
160. Test
IL‐6 (> 1.03 pg/ml), Othman 2008.
161
161. Test
IL‐6 (> 1.9 pg/ml), Othman 2008.
162
162. Test
IL‐6 (> 2.6 pg/ml), Othman 2008.
163
163. Test
IL‐6 (> 2 pg/ml), Bedaiwy 2002.
164
164. Test
IL‐6 (> 4 pg/ml), Bedaiwy 2002.
165
165. Test
IL‐6 (> 7.5 pg/ml), Bedaiwy 2002.
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References

References to studies included in this review

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Markham 1997a {published data only}
    1. Markham R, Fraser IS, Song JY, Young L, Chullapram T. Blood and peritoneal fluid concentrations of TNFalpha and RANTES in patients with and without endometriosis. Australian Journal of Medical Science 1997;18(4):116‐8.
Martinez 2007 {published data only}
    1. Martinez S, Garrido N, Coperias JL, Pardo F, Desco J, Garcia‐Velasco JA, et al. Serum interleukin‐6 levels are elevated in women with minimal‐mild endometriosis. Human Reproduction 2007;22(3):836‐42. - PubMed
Matalliotakis 2003a {published data only}
    1. Matalliotakis IM, Goumenou AG, Koumantakis GE, Neonaki MA, Koumantakis EE, Dionyssopoulou E, et al. Serum concentrations of growth factors in women with and without endometriosis: the action of anti‐endometriosis medicines. International Immunopharmacology 2003;3(1):81‐9. - PubMed
Matalliotakis 2004 {published data only}
    1. Matalliotakis IM, Arici A, Goumenou AG, Katassos T, Karkavitsas N, Koumantakis EE. Comparison of the effects of leuprorelin acetate and danazol treatments on serum CA‐125 levels in women with endometriosis. International Journal of Fertility and Women's Medicine 2004;49(2):75‐8. - PubMed
Matveeva 1990 {published data only}
    1. Matveeva NK, Volkov NI, Petrenko EP, Mit'kin VV, Pshenichnikova TI, Sukhikh GT. Immunological studies of peripheral blood in patients with external genital endometriosis and infertility. Akusherstvo i Ginekologiia 1990;8:48‐51. - PubMed
Mier‐Cabrera 2011 {published data only}
    1. Mier‐Cabrera J, Jimenez‐Zamudio L, Garcia‐Latorre E, Cruz‐Orozco O, Hernandez‐Guerrero C. Quantitative and qualitative peritoneal immune profiles, T‐cell apoptosis and oxidative stress‐associated characteristics in women with minimal and mild endometriosis. BJOG: An International Journal of Obstetrics and Gynaecology 2011;118(1):6‐16. - PubMed
Mihalyi 2010 {published data only}
    1. Mihalyi A, Gevaert O, Kyama CM, Simsa P, Pochet N, Smet F, et al. Non‐invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers. Human Reproduction 2010;25(3):654‐64. - PubMed
Mohamed 2013 {published data only}
    1. Mohamed ML, Behery MM, Mansour SAEA. Comparative study between VEGF‐A and CA‐125 in diagnosis and follow‐up of advanced endometriosis after conservative laparoscopic surgery. Archives of Gynecology and Obstetrics 2013;287(1):77‐82. - PubMed
Molo 1994 {published data only}
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Morin 2005 {published data only}
    1. Morin M, Bellehumeur C, Therriault MJ, Metz C, Maheux R, Akoum A. Elevated levels of macrophage migration inhibitory factor in the peripheral blood of women with endometriosis. Fertility and Sterility 2005;83(4):865‐72. - PubMed
Muscatello 1992 {published data only}
    1. Muscatello R, Cucinelli F, Fulghesu A, Lanzone A, Caruso A, Mancuso S. Multiple serum marker assay in the diagnosis of endometriosis. Gynecological Endocrinology 1992;6:265‐9. - PubMed
Odukoya 1996 {published data only}
    1. Odukoya O, Bansal A, Cooke I. Serum endometrial IgG antibodies and soluble CD23 concentrations in patients with endometriosis. Acta Obstetricia et Gynecologica Scandinavica 1996;75(10):927‐31. - PubMed
Ohata 2008 {published data only}
    1. Ohata Y, Harada T, Miyakoda H, Taniguchi F, Iwabe T, Terakawa N. Serum interleukin‐8 levels are elevated in patients with ovarian endometrioma. Fertility and Sterility 2008;90(4):994‐9. - PubMed
Oku 2004 {published data only}
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Olkowska‐Truchanowicz 2013 {published data only}
    1. Olkowska‐Truchanowicz J, Bocian K, Maksym RB, Bialoszewska A, Wlodarczyk D, Baranowski W, et al. CD4+ CD25+ FOXP3+ regulatory T cells in peripheral blood and peritoneal fluid of patients with endometriosis. Human Reproduction 2013;28(1):119‐24. - PubMed
Othman 2008 {published data only}
    1. Othman EEDR, Homung D, Salem HT, Khalifa EA, El‐Metwally TH, Al‐Hendy A. Serum cytokines as biomarkers for nonsurgical prediction of endometriosis. European Journal of Obstetrics, Gynecology, & Reproductive Biology 2008;137(2):240‐6. - PubMed
Ozhan 2014 {published data only}
    1. Ozhan E, Kokcu A, Yanik K, Gunaydin M. Investigation of diagnostic potentials of nine different biomarkers in endometriosis. European Journal of Obstetrics, Gynecology, & Reproductive Biology 2014;178:128‐33. - PubMed
Paiva 2014 {published data only}
    1. Paiva P, Lappas M, Barker G, Healey M. Using symptom scores, lifestyle measures and biochemical markers to create a test for endometriosis. Journal of Endometriosis 2014;6(3):135‐43.
Patton 1986 {published data only}
    1. Patton PE, Field CS, Harms RW, Coulam CB. CA‐125 levels in endometriosis. Fertility and Sterility 1986;45(6):770‐3. - PubMed
Philippoussis 2004 {published data only}
    1. Philippoussis F, Gagne D, Hugo P, Gosselin D. Concentrations of alpha‐fetoprotein, insulin‐like growth factor binding protein‐3, c‐erbB‐2, and epidermal growth factor in serum of patients with endometriosis. Journal of the Society for Gynecologic Investigation 2004;11(3):175‐81. - PubMed
Pittaway 1989 {published data only}
    1. Pittaway DE, Douglas JW. Serum CA‐125 in women with endometriosis and chronic pelvic pain. Fertility and Sterility 1989;51(1):68‐70. - PubMed
Podgaec 2007 {published data only}
    1. Podgaec S, Abrao MS, Dias Jr JA, Rizzo LV, Oliveira RM, Baracat EC. Endometriosis: An inflammatory disease with a Th2 immune response component. Human Reproduction 2007;22(5):1373‐9. - PubMed
Ramos 2012 {published data only}
    1. Ramos IML, Podgaec S, Abrao MS, Oliveira R, Baracat EC. Evaluation of CA‐125 and soluble CD‐23 in patients with pelvic endometriosis: A case‐control study. Revista da Associacao Medica Brasileira 2012;58(1):26‐32. - PubMed
Randall 2007 {published data only}
    1. Randall GW, Gantt PA, Poe‐Zeigler RL, Bergmann CA, Noel ME, Strawbridge WR, et al. Serum antiendometrial antibodies and diagnosis of endometriosis. American Journal of Reproductive Immunology 2007;58(4):374‐82. - PubMed
Riley 2007 {published data only}
    1. Riley CF, Moen MH, Videm V. Inflammatory markers in endometriosis: reduced peritoneal neutrophil response in minimal endometriosis. Acta Obstetricia et Gynecologica Scandinavica 2007;86(7):877‐81. - PubMed
Rosa E Silva 2007 {published data only}
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Rosa E Silva 2014 {published data only}
    1. Rosa ESJC, Do Amara VF, Mendonca JL, Rosa ESACJDS, Nakao LS, Neto OBP, et al. Serum markers of oxidative stress and endometriosis. Clinical and Experimental Obstetrics & Gynecology 2014;41(4):371‐4. - PubMed
Salehpour 2009 {published data only}
    1. Salehpour S, Sene AA, Mehrjerdi EK, Akhoond MR. The correlation between serum and peritoneal fluid CA125 level in women with pelvic endometriosis. International Journal of Fertility & Sterility 2009;3(1):29‐34.
Seeber 2008 {published data only}
    1. Seeber B, Sammel MD, Fan X, Gerton GL, Shaunik A, Chittams J, et al. Panel of markers can accurately predict endometriosis in a subset of patients. Fertility & Sterility 2008;89(5):1073‐81. - PubMed
Seeber 2010 {published data only}
    1. Seeber B, Sammel MD, Fan X, Gerton GL, Shaunik A, Chittams J, et al. Proteomic analysis of serum yields six candidate proteins that are differentially regulated in a subset of women with endometriosis. Fertility & Sterility 2010;93(7):2137‐44. - PMC - PubMed
Somigliana 2002 {published data only}
    1. Somigliana E, Vigano P, Candiani M, Felicetta I, Blasio AM, Vignali M. Use of serum‐soluble intercellular adhesion molecule‐1 as a new marker of endometriosis. Fertility & Sterility 2002;77(5):1028‐31. - PubMed
Somigliana 2004 {published data only}
    1. Somigliana E, Vigano P, Tirelli AS, Felicetta I, Torresani E, Vignali M, et al. Use of the concomitant serum dosage of CA 125, CA 19‐9 and interleukin‐6 to detect the presence of endometriosis. Results from a series of reproductive age women undergoing laparoscopic surgery for benign gynaecological conditions. Human Reproduction 2004;19(8):1871‐6. - PubMed
Steff 2004a {published data only}
    1. Steff AM, Gagne D, Page M, Rioux A, Hugo P, Gosselin D. Serum concentrations of insulin‐like growth factor‐1, soluble tumor necrosis factor receptor‐1 and angiogenin in endometriosis patients. American Journal of Reproductive Immunology 2004;51(2):166‐73. - PubMed
Suen 2014 {published data only}
    1. Suen JL, Chang Y, Chiu PR, Hsieh TH, Hsi E, Chen YC, et al. Serum level of IL‐10 is increased in patients with endometriosis, and IL‐10 promotes the growth of lesions in a murine model. American Journal of Pathology 2014;184(2):464‐71. - PubMed
Szczepanska 2001a {published data only}
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Szczepanska 2001b {published data only}
    1. Szczepanska M, Mikolajczyk M, Raczynska P, Skrzypczak J. The evaluation of IL‐12 levels in peritoneal fluid and serum of women with endometriosis. Ginekologia Polska 2001;72(5):408‐17. - PubMed
Szubert 2012 {published data only}
    1. Szubert M, Suzin J, Wierzbowski T, Kowalczyk‐Amico K. CA‐125 concentration in serum and peritoneal fluid in patients with endometriosis ‐ preliminary results. Archives of Medical Science 2012;8(3):504‐8. - PMC - PubMed
Szubert 2014 {published data only}
    1. Szubert M, Suzin J, Duechler M, Szuławska A, Czyż M, Kowalczyk‐Amico K. Evaluation of selected angiogenic and inflammatory markers in endometriosis before and after danazol treatment. Reproduction, Fertility, and Development 2014;26(3):414‐20. - PubMed
Thubert 2014 {published data only}
    1. Thubert T, Santulli P, Marcellin L, Menard S, M'Baye M, Streuli I, et al. Measurement of hs‐CRP is irrelevant to diagnose and stage endometriosis: prospective study of 834 patients. American Journal of Obstetrics and Gynecology 2014;210(6):533 e1‐e10. - PubMed
Tokmak 2011 {published data only}
    1. Tokmak A, Ugur M, Tonguc E, Var T, Moraloglu O, Ozaksit G. The value of urocortin and Ca‐125 in the diagnosis of endometrioma. Archives of Gynecology and Obstetrics 2011;283(5):1075‐9. - PubMed
Tuten 2014a {published data only}
    1. Tuten A, Kucur M, Imamoglu M, Kaya B, Acikgoz AS, Yilmaz N, et al. Copeptin is associated with the severity of endometriosis. Archives of Gynecology and Obstetrics 2014;290(1):75‐82. - PubMed
Vercellini 1993 {published data only}
    1. Vercellini P, Benedetti F, Rossi E, Colombo A, Trespidi L, Crosignani PG, et al. Tumor necrosis factor in plasma and peritoneal fluid of women with and without endometriosis. Gynecologic and Obstetric Investigation 1993; Vol. 36, issue 1:39‐41. - PubMed
Verit 2008 {published data only}
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Vigano 2002 {published data only}
    1. Vigano P, Somigliana E, Matrone R, Dubini A, Barron C, Vignali M, et al. Serum leptin concentrations in endometriosis. Journal of Clinical Endocrinology and Metabolism 2002;87(3):1085‐7. - PubMed
Vigil 1999 {published data only}
    1. Vigil PP, Aglony IM, Kolbach RM, Rubio AV, Villarroel Del Pino L. Endometriosis and CA 125 in women of reproductive age [Endometriosis y CA 125 en mujeres en edad reproductiva]. Revista Chilena de Obstetrica y Ginecologia 1999; Vol. 64, issue 5:385‐8.
Vodolazkaia 2011 {published data only}
    1. Vodolazkaia A, Bossuyt X, Fassbender A, Kyama CM, Meuleman C, Peeraer K, et al. A high sensitivity assay is more accurate than a classical assay for the measurement of plasma CRP levels in endometriosis. Reproductive Biology and Endocrinology 2011;9:113. - PMC - PubMed
Vodolazkaia 2012 {published data only}
    1. Vodolazkaia A, El‐Aalamat Y, Popovic D, Mihalyi A, Bossuyt X, Kyama CM, et al. Evaluation of a panel of 28 biomarkers for the non‐invasive diagnosis of endometriosis. Human Reproduction 2012;27:2698‐711. - PubMed
Vouk 2012 {published data only}
    1. Vouk K, Hevir N, Ribic‐Pucelj M, Haarpaintner G, Scherb H, Osredkar J, et al. Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis. Human Reproduction 2012;27(10):2955‐65. - PubMed
Wang 2013a {published data only}
    1. Wang WT, Zhao YN, Han BW, Hong SJ, Chen YQ, Wang X, et al. Circulating microRNAs identified in a genome‐wide serum microRNA expression analysis as noninvasive biomarkers for endometriosis [Study on polymorphism of human leukocyte antigen I in patients with endometriosis]. Journal of Clinical Endocrinology and Metabolism 2013;98(1):281‐9. - PubMed
Webster 2013 {published data only}
    1. Webster KE, Kennedy SH, Becker CM. Levels of circulating angiogenic cells are not altered in women with endometriosis. Human Reproduction 2013;28(3):651‐7. - PubMed
Wei 2005 {published data only}
    1. Wei XQ, Zhang Y, Tang M. Leptin levels and infertile patients with endometriosis. Zhongnan Daxue Xuebao (Yixue Ban) [Journal of Central South University (Medical Sciences)] 2005;30(4):487‐8. Chinese. - PubMed
Wild 1991a {published data only}
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Wolfler 2009 {published data only}
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Wu 1998 {published data only}
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Yagmur 2013 {published data only}
    1. Yagmur E, Bastu E, Karamustafaoglu‐Balci B, Akhan SE, Buyru F. Non‐invasive diagnosis of endometriosis based on a combined analysis of four plasma biomarkers. Central‐European Journal of Immunology 2013;38(2):154‐8.
Yang 1994 {published data only}
    1. Yang F, Fang AH, Gu RF. Value of CA125 (carbon hydrate tumor‐associated antigen) and endometrial antibodies for the detections of endometriosis. Zhonghua Fuchanke Zazhi [Chinese Journal of Obstetrics and Gynecology] 1994;29(3):147‐149, 189. Chinese. - PubMed
Yavuzcan 2013 {published data only}
    1. Yavuzcan A, Caglar M, Ustun Y, Dilbaz S, Ozdemir I, Yildiz E, et al. Evaluation of mean platelet volume, neutrophil/ lymphocyte ratio and platelet/lymphocyte ratio in advanced stage endometriosis with endometrioma [Endometrioma bulunan ileri evre endometrioziste ortalama trombosit hacmi, nötrofil/lenfosit orani ve trombosit/lenfosit oraninin degerlendirilmesi]. Journal of the Turkish German Gynecological Association 2013;14(4):210‐5. - PMC - PubMed
Zeng 2005 {published data only}
    1. Zeng F, Xue M, Zevallos HBV, Lai D, Arthur J, Ng C, et al. Diagnostic value of the detection of aromatase cytochrome P450 and CA125 for endometriosis. Zhongnan Daxue Xuebao (Yixue Ban) [Journal of Central South University (Medical Sciences)] 2005;30(6):682‐5. Chinese. - PubMed
Zhang 2005a {published data only}
    1. Zhang X, Lin J, Deng L, Chen Z, Chen L. Peritoneal fluid and serum concentration of interleukin‐16 in women with endometriosis. Acta Obstetricia et Gynecologica Scandinavica 2005;84(3):297‐8. - PubMed
Zhang 2005b {published data only}
    1. Zhang Y, Peng LX, Meng L. Measurements of interleukin‐18 in peritoneal fluid and serum of patients with endometriosis. Zhongnan Daxue Xuebao (Yixue Ban) [Journal of Central South University (Medical Sciences)] 2005;30(6):731‐2. Chinese. - PubMed
Zhang 2006a {published data only}
    1. Zhang C, Maeda N, Izumiya C, Yamamoto Y, Kusume T, Oguri H, et al. Killer immunoglobulin‐like receptor and human leukocyte antigen expression as immunodiagnostic parameters for pelvic endometriosis. American Journal of Reproductive Immunology 2006;55(2):106‐14. - PubMed
Zhang 2006b {published data only}
    1. Zhang R, Luo R. Soluble intercellular adhesion molecule 1 in serum and peritoneal fluid on patients with endometriosis. Wuhan Yike Daxue Xuebao (Yixueban) [Medical Journal of Wuhan University] 2006;27(1):97‐9. Chinese.

References to studies excluded from this review

Abdallah 2006 {published data only}
    1. Abdallah MA, Kang S, Nakajima ST, Gercel‐Taylor C. Matrix metalloproteinase‐9 activity in the plasma of patients after surgical resection of endometriomas. Fertility and Sterility 2006;85(6):1847‐8. - PubMed
Abrao 1997 {published data only}
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Abrao 1999 {published data only}
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Acien 2007 {published data only}
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Adamyan 1993 {published data only}
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Agic 2007 {published data only}
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Alcazar 2011 {published data only}
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Amaral 2006 {published data only}
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Ammendola 2008 {published data only}
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Anastasi 2013 {published data only}
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Antsiferova 2005 {published data only}
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Arjona Berral 1996 {published data only}
    1. Arjona Berral JE, Contreras Puertas PI, Torres Avisbal M, Pacheco Capote C, Vallejo Casas JA, Benitez Velasco A, et al. Serum CA 125 and CA 19.9 levels in the diagnosis of patients with suspected endometriosis [Niveles sericos de CA‐125 y CA 19.9 en el diagnostico de pacientes con sospecha clinica de endometriosis]. Revista Espanola de Medicina Nuclear 1996;15(2):71‐6.
Avcioglu 2014 {published data only}
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Ayers 1987 {published data only}
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Badawy 1984 {published data only}
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Badawy 1987 {published data only}
    1. Badawy SZ, Cuenca V, Stitzel A, Tice D. Immune rosettes of T and B lymphocytes in infertile women with endometriosis. Journal of Reproductive Medicine 1987;32(3):194‐7. - PubMed
Badawy 1990 {published data only}
    1. Badawy SZA, Cuenca V, Freliech H, Stefanu C. Endometrial antibodies in serum and peritoneal fluid of infertile patients with and without endometriosis. Fertility and Sterility 1990;53(5):930‐2. - PubMed
Balasch 1985 {published data only}
    1. Balasch J, Vanrell JA. Mild endometriosis and luteal function. International Journal of Fertility 1985;30(3):4‐6. - PubMed
Barbieri 1986 {published data only}
    1. Barbieri RL, Niloff JM, Bast RC Jr, Scaetzl E, Kistner RW, Knapp RC. Elevated serum concentrations of CA‐125 in patients with advanced endometriosis. Fertility and Sterility 1986;45(5):630‐4. - PubMed
Barbieri 1987 {published data only}
    1. Barbieri RL. CA‐125 and endometriosis. Contributions to Gynecology and Obstetrics 1987;16:103‐8. - PubMed
Barrier 2002 {published data only}
    1. Barrier F, Sharpe‐Timms KL. Expression of soluble adhesion molecules in sera of women with stage III and IV endometriosis. Journal of the Society for Gynecologic Investigation 2002;9(2):98‐101. - PubMed
Basta 2009 {published data only}
    1. Basta P, Mach P, Pitynski K, Bednarek W, Klimek M, Zietek J, et al. Differences in the blood serum levels of soluble HLA‐G concentrations between the menstrual cycle phases and menopause in patients with ovarian endometriosis and uterine leiomyoma. Neuroendocrinology Letters 2009;30(1):91‐8. - PubMed
Bedaiwy 2006 {published data only}
    1. Bedaiwy MA, Falcone T, Mascha EJ, Casper RF. Genetic polymorphism in the fibrinolytic system and endometriosis. Obstetrics and Gynecology 2006;108(1):162‐8. - PubMed
Berkes 2013 {published data only}
    1. Berkes E, Muzinic A, Rigo Jr J, Tinneberg HR, Oehmke F. The analysis of the human plasma N‐glycome in endometriosis patients. European Journal of Obstetrics, Gynecology, & Reproductive Biology 2013;171(1):107‐15. - PubMed
Bianchi 2003 {published data only}
    1. Bianchi M, Macaya R, Durruty G, Manzur A. Correlation between CA‐125 marker with the presence and severity of pelvic endometriosis. Revista Medica de Chile 2003;131(4):367‐72. - PubMed
Bohler 2007 {published data only}
    1. Bohler HC, Gercel‐Taylor C, Lessey BA, Taylor DD. Endometriosis markers: immunologic alterations as diagnostic indicators for endometriosis. Reproductive Sciences 2007;14(6):595‐604. - PubMed
Bordin 2010 {published data only}
    1. Bordin L, Fiore C, Dona G, Andrisani A, Ambrosini G, Faggian D, et al. Evaluation of erythrocyte band 3 phosphotyrosine level, glutathione content, CA‐125, and human epididymal secretory protein E4 as combined parameters in endometriosis. Fertility and Sterility 2010;94(5):1616‐21. - PubMed
Bourlev 2006a {published data only}
    1. Bourlev V, Larsson A, Olovsson M. Elevated levels of fibroblast growth factor‐2 in serum from women with endometriosis. American Journal of Obstetrics and Gynecology 2006;194(3):755‐9. - PubMed
Bourlev 2006b {published data only}
    1. Bourlev V, Volkov N, Pavlovitch S, Lets N, Larsson A, Olovsson M. The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor‐A and its receptors in eutopic endometrium and endometriotic lesions. Reproduction 2006;132(3):501‐9. - PubMed
Bragatto 2013 {published data only}
    1. Bragatto FB, Barbosa CP, Christofolini DM, Peluso C, dos Santos AA, Mafra FA, et al. There is no relationship between Paraoxonase serum level activity in women with endometriosis and the stage of the disease: an observational study. Reproductive Health 2013;10:32. - PMC - PubMed
Brinton 1996 {published data only}
    1. Brinton DA, Quattrociocchi‐Longe TM, Kiechle FL. Endometriosis: identification by carbonic anhydrase autoantibodies and clinical features. Annals of Clinical and Laboratory Science 1996;26(5):409‐20. - PubMed
Brosens 1978 {published data only}
    1. Brosens IA, Koninckx PR, Corveleyn PA. A study of plasma progesterone, oestradiol‐17beta, prolactin and LH levels, and of the luteal phase appearance of the ovaries in patients with endometriosis and infertility. British Journal of Obstetrics and Gynaecology 1978;85(4):246‐50. - PubMed
Cai 2005 {published data only}
    1. Cai ZH, He YL, Peng DX. Changes of serum epithelial neutrophil‐activating peptide‐78 in patients with endometriosis. Di 1 Junyi Daxue Xuebao [Academic Journal of the First Medical College of PLA] 2005;25(4):464‐5. Chinese. - PubMed
Carmona 2012 {published data only}
    1. Carmona F, Chapron C, Martinez‐Zamora M‐A, Santulli P, Rabanal A, Martinez‐Florensa M, et al. Ovarian endometrioma but not deep infiltrating endometriosis is associated with increased serum levels of interleukin‐8 and interleukin‐6. Journal of Reproductive Immunology 2012;95(1‐2):80‐6. - PubMed
Cheng 2002 {published data only}
    1. Cheng YM, Wang ST, Chou CY. Serum CA‐125 in preoperative patients at high risk for endometriosis. Obstetrics and Gynecology 2002;99(3):375‐80. - PubMed
Chihal 1986 {published data only}
    1. Chihal HJ, Mathur S, Holtz GL, Williamson HO. An endometrial antibody assay in the clinical diagnosis and management of endometriosis. Fertility and Sterility 1986;46:408‐11. - PubMed
Cho 2008 {published data only}
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Cunha‐Filho 2001 {published data only}
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Dias 2006 {published data only}
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Fernandez‐Shaw 1993 {published data only}
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Fisk 1988 {published data only}
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Guerriero 1997 {published data only}
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Hornstein 1992 {published data only}
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Hrycek 1996 {published data only}
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Hsu 2014 {published data only}
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Illera 2001 {published data only}
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Jackson 2005 {published data only}
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Ozaksit 1995 {published data only}
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Pittaway 1986 {published data only}
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Sharpe‐Timms 1998 {published data only}
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Suryawanshi 2013 {published data only}
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Takahashi 1987 {published data only}
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Takahashi 1989 {published data only}
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Wild 1992 {published data only}
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Zomer 2013 {published data only}
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References to ongoing studies

JPRN‐UMIN000009223 {published data only}
    1. Analysis of miRNA in blood for development of diagnostic biomarkers for endometriosisClinicalTrials.gov Identifier: JPRN‐UMIN000009223Primary sponsor: Juntendo University Hospital, Department of Obstetrics and Gynecology. Ongoing study February 2013.
NCT01301885 {published data only}
    1. ENDOMET ‐ Novel diagnostic tools and treatments for endometriosisClinicalTrials.gov Identifier: NCT01301885Other study name: CA125_VAS_changes. Ongoing study February 2011.
NCT02091557 {published data only}
    1. CA‐125 and VAS pain score changes to diagnose endometriosisClinicalTrials.gov Identifier: NCT02091557Other study name: CA125_VAS_changes. Ongoing study January 2011.
NCT02337816 {published and unpublished data}
    1. Role of metabolomics in the diagnosis of endometriosisClinicalTrials.gov Identifier: NCT02337816Other study name: ENDOMETAB01. Ongoing study December 2014.

Additional references

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