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Author, year and reference

OS marker

Evidence

Study group (N)

Controls (N)

Results

A. Seminal OS markers

1.

Hendin et al. 1999 [104]

Seminal ROS (by CL)

Direct

Infertile (21) and fertile (15) men with varicocele

Sperm donors without varicocele (17)

Higher ROS levels in infertile & fertile men with varicocele

2.

Sharma et al. 1999 [145]

Seminal ROS (by CL)

Direct

Infertile men with varicocele (56)

Sperm donors (24)

Higher ROS levels in men with varicocele

3.

Pasqualotto et al. 2000 [146]

Seminal ROS (by CL)

Direct

Infertile men with varicocele (77)

Fertile men (19)

Higher ROS levels in varicocele

4.

Pasqualotto et al. 2001 [147]

Seminal ROS (by CL)

Direct

Infertile normospermic men with varicocele (16)

Healthy donors (19)

High ROS levels in varicocele group

5.

Nallella 2004 [144]

Seminal ROS levels by chemiluminescence assay

Direct

35 infertile men with varicocele

15 fertile donors

Significant elevation of ROS in semen of men with varicocele

6.

Allamaneni et al. 2004 [62]

Seminal ROS (by CL)

Direct

Infertile men with grades 2 and 3 left varicocele

Infertile men with grade 1 left varicocele

Higher ROS levels in grade 2–3 varicocele compared to grade 1

7.

Smith et al. 2006 [72]

Seminal ROS levels by chemiluminescence assay

Direct

55 with clinical varicocele, divided into normospermic and oligozoospermic

25 normozoospermic donors

ROS levels were significantly higher (P < 0.01) in both groups of patients with varicocele

8.

Pasqualotto et al. 2008 [105]

Seminal ROS (by CL)

Direct

Infertile men with varicocele (21), fertile men with varicocele (15)

Fertile men (17)

Higher ROS in varicocele group

9.

Dada 2010 [74]

Seminal ROS levels by (CL)

Direct

Infertile with varicocele (11)

Healthy men (15)

Higher ROS in varicocele group

10.

Mehraban et al. 2005 [150]

Seminal NO by Griess reaction

Direct

Infertile with varicocele (40)

Infertile men without varicocele (N = 40) and healthy men (40)

Significant rise in No level in semen of men with varicocele compared to other groups

11.

Xu 2008 [151]

Seminal NO, and NO synthase (NOS)

Direct

Infertile men with varicocele (53)

Infertile men (29), fertile men (28)

Higher seminal NO level and NOS activity in men with varicocele compared to infertile men and healthy donors

12.

Sakamoto et al. 2008 [149]

Seminal NO using NO2/NO3 assay kit, 8- hydroxy-2 deoxyguanosine (8-OHdG), hexanoyl-lysine (HEL)

Direct and indirect

Oligozoospermic (15) & normozoospermic men (15) with varicocele

Normozoospermic & oligozoospermic infertile men (15) without varicocele

Higher NO, HEL 8-OHdG concentration levels in varicocele group

13.

Abd-Elmoaty 2010 [152]

Seminal MDA Colorimetric method), NO

Direct and Indirect

Infertile men with varicocele (36)

Fertile men with normal genital examination (18)

Infertile men with varicoceles showed increased levels of MDA and NO

14.

Mazzilli 1996 [154]

Extracellular seminal superoxide anion (O2-) measured by cytochrome C reduction assay

Direct

Infertile men including varicocele (132)

Fertile normozoospermic (20)

Significant increase in superoxide anion in semen of infertile men with varicocele compared to fertile men

15.

Yesilli et al. 2005 [155]

Seminal MDA

Indirect

Infertile men with varicocele (56)

Healthy men (25)

Higher seminal MDA in the varicocele group

16.

Mostafa et al. 2011 [153]

Seminal MDA, hydrogen peroxide (H₂O)

Direct and indirect

Infertile OAT men with varicocele (89)

Healthy fertile controls (20)

Grades II, III demonstrated significant increase in estimated seminal MDA, H2O2

17.

Akyol 2001 [157]

Seminal MDA (TBARS), SOD

Indirect

Varicocele patients with abnormal semen parameters (13) and varicocele patients with normal semen (12)

Healthy men (10)

No significant differences among various study groups

18.

Blumer et al. 2011 [71]

Seminal MDA

Indirect

Patients with a clinically diagnosed varicocele of grade II or III (30)

Men without varicocele (32)

No significant differences

19.

Mostafa et al. 2009 [106]

Seminal MDA (TBARS), H₂O₂

Direct and indirect

Infertile (42) and fertile 45) men with varicocele

Fertile men without varicocele (45)

High ROS levels in varicocele groups vs. fertile men

B. Testicular biopsy

1.

Koksal 2000 [63]

Tissue MDA levels

Indirect

15 infertile men with varicocele

10 infertile without varicocele

Higher tissue MDA levels in infertile men with varicocele and this rise is grade related

2.

Santoro et al. 2001 [158]

NO synthase (NOS) activity in testicular biopsy specimen

Direct

20 adolescents with varicocele

8 adolescents without varicocele

The iNOS is up-regulated in Leydig cells and endothelial cells in adolescents with varicocele

3.

Shiraishi et al. 2005 [101]

Generation of 4-HNE-modified proteins and Expression of Leydig cell HO-1

Indirect

30 patients with varicocele

10 healthy

Increased generation of 4-HNE-modified proteins was observed in varicocele testes and increased in Leydig cell HO-1

4.

Shirashi 2007 [159]

Intratesticular fluid NO level, testicular biopsy NOS

Direct

27 patients with varicocele

5

Increased Intratesticular level of NO and activity of iNOS in men with grade 2 and grade 3 varicocele compared to controls

5.

Ishikawa 2007 [160]

Testicular tissue 8-hydroxy-2’-deoxyguanosine (8-OHdG assessed by immunohistochemistry

Indirect

36 patients with varicocele

5

Immunostained germ cells were significantly more prevalent in the varicocele group

6.

Shirashi et al. 2009 [78]

Testicular tissue 4-HNE-modified proteins

Indirect

30 infertile men with varicocele

12 fertile men with varicocele and 10 fertile with no varicocele

Tissue 4-HNE-modified proteins was higher among infertile men with varicocele than fertile men with and without varicocele and in the left testis more than the right

7.

Shirashi 2010 [161]

Testicular tissue 4-HNE-modified proteins

Indirect

32 infertile men with varicocele

8 healthy men

Scrotal temperature elevation is associated with higher production of 4-HNE-modified proteins