Peripheral biomarkers of endometriosis: a systematic review.
BACKGROUND
Endometriosis is estimated to affect 1 in 10 women during the reproductive years. There is often delay in making the diagnosis, mainly due to the non-specific nature of the associated symptoms and the need to verify the disease surgically. A biomarker that is simple to measure could help clinicians to diagnose (or at least exclude) endometriosis; it might also allow the effects of treatment to be monitored. If effective, such a marker or panel of markers could prevent unnecessary diagnostic procedures and/or recognize treatment failure at an early stage.


METHODS
We used QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to perform a systematic review of the literature over the last 25 years to assess critically the clinical value of all proposed biomarkers for endometriosis in serum, plasma and urine.


RESULTS
We identified over 100 putative biomarkers in publications that met the selection criteria. We were unable to identify a single biomarker or panel of biomarkers that have unequivocally been shown to be clinically useful.


CONCLUSIONS
Peripheral biomarkers show promise as diagnostic aids, but further research is necessary before they can be recommended in routine clinical care. Panels of markers may allow increased sensitivity and specificity of any diagnostic test.
May
K E
KE
Nuffield Department of Obstetrics & Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Conduit-Hulbert
S A
SA
Villar
J
J
Kirtley
S
S
Kennedy
S H
SH
Becker
C M
CM
D000906:Antibodies / Q000097:blood / Q000378:metabolism / Q000652:urine; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood / Q000378:metabolism* / Q000652:urine; D002448:Cell Adhesion; D016207:Cytokines / Q000097:blood / Q000378:metabolism / Q000652:urine; D004715:Endometriosis / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006728:Hormones / Q000097:blood; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007962:Leukocytes / Q000473:pathology / Q000502:physiology; D040901:Proteomics; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000652:urine
D000906:Antibodies; D015415:Biomarkers; D016207:Cytokines; D006023:Glycoproteins; D006728:Hormones; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A
Eur J Obstet Gynecol Reprod Biol. 2005 Dec 1;123(2):198-203
16046047
Clin Exp Immunol. 1982 Nov;50(2):259-66
6759000
Hum Reprod. 2005 Oct;20(10):2698-704
15980014
Am J Obstet Gynecol. 1991 Dec;165(6 Pt 1):1857-64
1721486
Hum Reprod. 2009 Dec;24(12):3019-24
19690352
J Reprod Med. 1991 Mar;36(3):177-82
2030493
Arch Gynecol Obstet. 2009 Jun;279(6):891-5
19023580
Fertil Steril. 1998 Dec;70(6):1139-42
9848307
Eur J Obstet Gynecol Reprod Biol. 2005 Oct 1;122(2):199-205
15893866
J Reprod Med. 1999 May;44(5):450-4
10360259
Postepy Hig Med Dosw (Online). 2008 Mar 03;62:103-9
18334925
Eur J Cancer. 2006 Apr;42(6):793-802
16524718
Eur J Med Res. 2007 Apr 26;12(4):145-51
17509958
Am J Reprod Immunol. 1998 Aug;40(2):69-73
9764347
Obstet Gynecol. 1991 Jun;77(6):927-31
2030870
Obstet Gynecol. 1993 May;81(5 ( Pt 1)):665-8
8469451
J Exp Med. 1995 Dec 1;182(6):1777-83
7500022
Obstet Gynecol. 2007 Sep;110(3):594-600
17766605
Prenat Diagn. 2008 Mar;28(3):247-53
18302310
Obstet Gynecol. 2000 Jun;95(6 Pt 1):810-3
10831972
Fertil Steril. 2007 Apr;87(4):982-4
17261287
Hum Reprod Update. 2009 Jul-Aug;15(4):441-61
19279046
Am J Obstet Gynecol. 1988 Jun;158(6 Pt 1):1365-73
3132855
Am J Reprod Immunol. 2006 Feb;55(2):106-14
16433829
Clin Pharmacol Ther. 2001 Mar;69(3):89-95
11240971
J Reprod Med. 1992 Jun;37(6):552-6
1535659
Fertil Steril. 1990 Feb;53(2):242-5
2298309
Pediatr Nephrol. 2009 Jan;24(1):105-11
18800229
Reprod Biomed Online. 2009 Mar;18(3):407-11
19298741
Eur J Obstet Gynecol Reprod Biol. 2005 Dec 1;123(2):254-5
15893865
Sao Paulo Med J. 2006 Jul 6;124(4):223-7
17086305
Fertil Steril. 1989 May;51(5):774-80
2651165
Am J Obstet Gynecol. 1989 Oct;161(4):866-71
2801831
Lancet. 2004 Nov 13-19;364(9447):1789-99
15541453
Gynecol Obstet Invest. 2002;54(2):82-7
12566749
Gynecol Endocrinol. 2004 Mar;18(3):144-51
15255283
Hum Reprod. 2004 Jan;19(1):172-8
14688178
Acta Obstet Gynecol Scand. 1996 Nov;75(10):927-31
9003095
Int J Biochem Cell Biol. 1997 Nov;29(11):1231-4
9451819
Cytokine. 1997 May;9(5):370-4
9195137
Immunol Rev. 1986 Jun;91:39-60
2426181
Int J Fertil Womens Med. 2004 Mar-Apr;49(2):75-8
15188832
Fertil Steril. 2009 Feb;91(2):350-8
18314105
Reproduction. 2001 May;121(5):761-9
11427164
Science. 1995 Mar 10;267(5203):1449-56
7533326
Am J Reprod Immunol. 2007 Dec;58(6):497-504
17997748
Hum Reprod. 1997 Nov;12(11):2523-7
9436699
Fertil Steril. 1999 Nov;72(5):857-67
10560990
Hum Reprod. 2009 Oct;24(10):2600-6
19549703
Int J Gynaecol Obstet. 2007 Oct;99(1):33-7
17602688
Gynecol Endocrinol. 1992 Mar;6(1):19-24
1580163
Fertil Steril. 2004 May;81(5):1441-6
15136136
Gynecol Endocrinol. 1992 Dec;6(4):265-9
1492582
Fertil Steril. 2008 May;89(5):1073-1081
17706208
Hum Reprod. 2007 Mar;22(3):836-42
17062580
J Cell Biol. 1992 Nov;119(3):629-41
1383237
J Endocrinol. 2002 May;173(2):R9-14
12010647
Hum Reprod Update. 2007 Jul-Aug;13(4):395-404
17584822
Int J Fertil. 1993 Mar-Apr;38(2):92-8
8097504
Fertil Steril. 2003 Oct;80(4):889-94
14556808
Acta Obstet Gynecol Scand. 1993 Apr;72(3):157-61
8385848
Fertil Steril. 2008 Oct;90(4):994-9
18635170
Hum Reprod. 2008 Jan;23(1):100-4
18000171
Am J Clin Pathol. 1994 May;101(5):611-5
8178769
Fertil Steril. 2002 Feb;77(2):297-302
11821086
Reprod Biomed Online. 2008 Jun;16(6):817-24
18549691
Fertil Steril. 2007 Apr;87(4):988-90
17207800
Autoimmunity. 1999;29(2):121-7
10433073
Int J Fertil Womens Med. 1997 May-Jun;42(3):211-4
9222806
Fertil Steril. 1998 Jun;69(6):1128-34
9627304
Fertil Steril. 1991 Jul;56(1):45-51
2065804
Circ Heart Fail. 2009 Sep;2(5):465-71
19808377
Fertil Steril. 1988 Dec;50(6):864-71
3060379
Obstet Gynecol. 1998 Jan;91(1):25-9
9464715
Obstet Gynecol. 1992 May;79(5 ( Pt 1)):743-6
1565359
Reprod Sci. 2007 Sep;14(6):595-604
17959888
Am J Reprod Immunol. 2004 Feb;51(2):166-73
14748845
Hum Reprod. 2005 Jul;20(7):1999-2003
15890727
Fertil Steril. 2004 May;81(5):1235-9
15136083
Reprod Sci. 2008 Nov;15(9):906-11
19050323
Fertil Steril. 1985 Dec;44(6):772-7
4076434
Fertil Steril. 2007 Nov;88(5):1298-303
17482181
Am J Obstet Gynecol. 2000 Jul;183(1):58-62
10920309
Int J Fertil Menopausal Stud. 1993 Jul-Aug;38(4):229-34
8401682
Am J Reprod Immunol. 2009 Sep;62(3):187-95
19694644
BMJ. 2005 Apr 2;330(7494):753
15681569
Am J Reprod Immunol. 1996 Feb;35(2):118-22
8839140
Fertil Steril. 2006 Aug;86(2):274-82
16750201
Hum Reprod. 2003 Aug;18(8):1674-80
12871881
Fertil Steril. 2003 Aug;80(2):300-4
12909491
Ultrasound Obstet Gynecol. 2002 Dec;20(6):630-4
12493057
Am J Reprod Immunol. 2007 Oct;58(4):374-82
17845208
Fertil Steril. 2005 Dec;84(6):1705-11
16359969
Braz J Med Biol Res. 2006 Aug;39(8):1121-7
16906287
Fertil Steril. 1990 Jul;54(1):56-63
2358092
J Obstet Gynaecol Res. 2000 Apr;26(2):141-9
10870308
Eur J Obstet Gynecol Reprod Biol. 2008 Apr;137(2):240-6
17582674
Fertil Steril. 2007 Dec;88(6):1700-2
17482609
Fertil Steril. 1990 May;53(5):930-2
2332066
Am J Reprod Immunol. 2004 May;51(5):364-72
15212673
Fertil Steril. 1995 Feb;63(2):314-21
7531162
Am J Reprod Immunol. 2000 Mar;43(3):160-6
10735592
Hum Reprod. 1995 May;10(5):1214-9
7657768
Fertil Steril. 2002 Oct;78(4):855-9
12372468
Chin Med Sci J. 2004 Mar;19(1):56-9
15104227
Fertil Steril. 2010 May 1;93(7):2137-44
19230876
Arch Gynecol Obstet. 2006 Jan;273(4):227-31
16208475
J Reprod Immunol. 2001 Jul;51(1):9-19
11438377
Am J Obstet Gynecol. 1996 Dec;175(6):1620-5
8987950
Br J Obstet Gynaecol. 1997 Jan;104(1):78-81
8988701
Fertil Steril. 1986 Dec;46(6):1077-82
3781023
Fertil Steril. 2002 Apr;77(4):679-83
11937115
Blood. 1995 Aug 15;86(4):1243-54
7632928
Fertil Steril. 2002 Oct;78(4):733-9
12372448
Am J Reprod Immunol. 2001 Apr;45(4):232-8
11327550
Gynecol Obstet Invest. 2008;66(1):47-52
18311079
Int J Gynaecol Obstet. 2007 Mar;96(3):206-7
17289049
Horm Metab Res. 2001 Apr;33(4):216-20
11383925
JAMA. 1994 May 25;271(20):1615-9
8182815
Int J Gynaecol Obstet. 1999 Jul;66(1):19-22
10458545
Curr Opin Obstet Gynecol. 2003 Dec;15(6):519-22
14624220
Eur Respir J. 2008 Jan;31(1):140-2
17804443
Hum Reprod. 2003 Aug;18(8):1681-5
12871882
BJU Int. 2009 Mar;103(5):694-7
19040529
J Reprod Med. 1987 Aug;32(8):605-8
3656300
Hum Reprod. 2004 Aug;19(8):1871-6
15218003
J Obstet Gynaecol Res. 2007 Aug;33(4):490-5
17688616
Int J Cancer. 1983 Jun 15;31(6):711-4
6190763
Obstet Gynecol. 2001 Aug;98(2):258-64
11506842
Gynecol Obstet Invest. 1993;36(1):39-41
8349177
Int J Gynaecol Obstet. 2008 Jun;101(3):253-8
18325521
Fertil Steril. 2009 Nov;92(5):1761-3
19631319
Fertil Steril. 1996 Oct;66(4):547-56
8816615
JAMA. 2000 Apr 19;283(15):2008-12
10789670
Am J Reprod Immunol Microbiol. 1987 Mar;13(3):78-82
3605484
Gynecol Obstet Invest. 2006;62(3):136-8
16679771
Hum Reprod. 1998 Nov;13(11):3206-10
9853882
Mediators Inflamm. 2003 Jun;12(3):131-8
12857596
Immunol Invest. 2008;37(1):43-61
18214799
Biomed Pharmacother. 2004 Jan;58(1):24-38
14739059
J Endocrinol Invest. 1988 Dec;11(11):801-4
3225401
Arch Gynecol Obstet. 2009 Mar;279(3):361-4
18665375
FEBS Lett. 1992 Jul 27;307(1):97-101
1639201
Acta Obstet Gynecol Scand. 2006;85(4):458-66
16612709
Fertil Steril. 2009 Jan;91(1):46-50
18206876
Am J Reprod Immunol. 1996 May;35(5):483-94
8738720
Hum Reprod. 1998 Jul;13(7):1957-61
9740457
PLoS One. 2008 Aug 28;3(8):e3081
18769481
Fertil Steril. 2005 Apr;83(4):865-72
15820792
Hum Reprod. 1996 Apr;11(4):878-80
8671344
Hum Reprod. 2005 Dec;20(12):3510-3
16055459
Biol Reprod. 1998 Apr;58(4):988-94
9546730
Eur J Obstet Gynecol Reprod Biol. 2004 Sep 10;116(1):85-8
15294374
Fertil Steril. 2009 Oct;92(4):1221-1227
19022433
Am J Reprod Immunol. 2009 Apr;61(4):286-93
19260859
Fertil Steril. 2004 Jun;81(6):1507-12
15193469
Malays J Pathol. 1991 Jun;13(1):43-5
1795561
Fertil Steril. 1991 Jan;55(1):90-4
1986975
J Reprod Med. 1994 Dec;39(12):964-6
7884754
Fertil Steril. 2003 Jul;80(1):43-53
12849800
Gynecol Obstet Invest. 1996;42(3):183-6
8938471
Obstet Gynecol. 1984 Mar;63(3):271-5
6422368
Hum Reprod. 1995 Oct;10(10):2671-5
8567790
Fertil Steril. 2009 Feb;91(2):331-4
18281042
Ultrasound Obstet Gynecol. 2003 May;21(5):480-5
12768561
Fertil Steril. 1997 Jun;67(6):1059-64
9176444
BMC Med Res Methodol. 2003 Nov 10;3:25
14606960
J Soc Gynecol Investig. 2003 Feb;10(2):118-21
12594002
Eur J Gynaecol Oncol. 1998;19(5):498-500
9863924
J Immunol. 1995 Aug 1;155(3):1151-64
7636184
Hum Reprod. 2007 Dec;22(12):3159-69
17956924
Fertil Steril. 2009 Jun;91(6):2331-7
18555242
Chin Med Sci J. 2002 Jun;17(2):121-3
12906167
J Soc Gynecol Investig. 2002 Mar-Apr;9(2):98-101
11963839
J Reprod Med. 1987 Mar;32(3):194-7
3494842
J Soc Gynecol Investig. 2004 Apr;11(3):175-81
15051037
J Clin Endocrinol Metab. 2002 Mar;87(3):1085-7
11889169
Fertil Steril. 1998 Sep;70(3):425-31
9757870
Eur J Obstet Gynecol Reprod Biol. 2007 May;132(1):107-10
16698169
Fertil Steril. 2002 May;77(5):1028-31
12009362
Hum Reprod. 1995 Apr;10(4):942-6
7650148
Fertil Steril. 2006 Sep;86(3):554-8
16879825
Fertil Steril. 2003 Sep;80 Suppl 2:768-75
14505752
Lancet. 1978 Apr 29;1(8070):896-8
76843
Fertil Steril. 2008 Dec;90(6):2073-9
18555226
Hum Reprod. 2002 Feb;17(2):426-31
11821289
Hum Reprod. 2003 Mar;18(3):544-9
12615822
Acta Obstet Gynecol Scand. 2005 Mar;84(3):297-8
15715540
Chin Med J (Engl). 2009 Feb 20;122(4):373-6
19302738
Curr Biol. 1999 Dec 16-30;9(24):1441-7
10607586
Fertil Steril. 2009 Feb;91(2):320-4
18295214
Fertil Steril. 1991 Feb;55(2):436-7
1991544
Reproduction. 2006 Sep;132(3):501-9
16940291
Fertil Steril. 1998 Dec;70(6):1101-8
9848302
Hum Reprod. 2009 Dec;24(12):3025-32
19690351
Am J Reprod Immunol Microbiol. 1985 Jul;8(3):84-6
3895994
Acta Obstet Gynecol Scand. 1998 Jul;77(6):665-70
9688246
Fertil Steril. 2005 May;83(5):1536-43
15866595
Clin Exp Immunol. 1991 Dec;86(3):356-9
1836159
Mol Cell Endocrinol. 1996 Jan 15;116(1):105-14
8822271
Fertil Steril. 1987 Feb;47(2):218-24
3817170
Am J Obstet Gynecol. 2006 Mar;194(3):755-9
16522409
J Clin Endocrinol Metab. 2000 Jul;85(7):2483-7
10902797
Di Yi Jun Yi Da Xue Xue Bao. 2003 Aug;23(8):757-60
12919890
Fertil Steril. 1999 Jun;71(6):1115-8
10360920
Am J Reprod Immunol. 1994 Jan;31(1):25-31
8166944
Int J Biol Markers. 2007 Jul-Sep;22(3):200-2
17922463
Obstet Gynecol Clin North Am. 2003 Mar;30(1):95-114, viii-ix
12699260