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Table 2 Seminal plasma biomarkers for predicting successful sperm retrieval in men with nonobstructive azoospermia

From: Seminal plasma biomarkers for predicting successful sperm retrieval in patients with nonobstructive azoospermia: a narrative review of human studies

Year

Authors

Sample size

Predictors

Results

Country

1999

Fénichel

et al. [11]

10 NOA men with positive surgical sperm extraction and 13 NOA men with negative surgical sperm extraction.

AMH

In NOA group, comparison of seminal AMH concentration and the results of histological analysis of testicular biopsies revealed that undetectable AMH found in 14 cases was associated in 11 of them with lack of spermatozoa, whereas detectable concentrations of AMH (10–68.5 pmol/L) found in nine cases were associated in seven of them with persistent spermatogenesis (no surgical method provided).

France

2005

Nagata

et al. [12]

17 NOA men with TESE (+) and 45 NOA men with TESE (-).

INHB

The seminal inhibin B concentrations were significantly higher in the TESE (+) group compared with the TESE (−) group.

Japan

2007

Mostafa

et al. [13]

19 NOA men with TESE (+) and 21 NOA men with TESE (-).

AMH

There were no significant differences in terms of AMH between TESE (+) and TESE (−) patients.

Egypt

2008

Duvilla et al. [14]

11 NOA men with TESE (+) and 15 NOA men with TESE (-).

AMH and INHB

There were no significant differences in terms of AMH and inhibin B between TESE (+) and TESE (−) patients.

France

2009

Roshdy

et al. [15]

24 NOA men with TESE (+) and 13 NOA men with TESE (-).

Survivin

Seminal survivin was detectable in TESE (+) men but not in TESE (−) men.

Egypt

2010

Sabetian et al. [16]

8 NOA men with TESE (+) and 70 NOA men with TESE (-).

fructose, NAG, INHB, and AMH

There were significant differences in inhibin B and AMH concentrations between TESE (+) and TESE (−) patients. There were no differences regarding the levels of NAG and fructose between TESE (+) and TESE (−) patients.

Iran

2010

Mitchell

et al. [17]

60 NOA men with TESE (+) and 79 NOA men with TESE (-).

AMH and INHB

TESE (+) and TESE (−) patients did not differ significantly in terms of either AMH or inhibin B seminal plasma concentrations.

France

2011

Ma et al. [18]

110 NOA men with TESE (+) and 170 NOA men with TESE (-).

leptin, alpha-glucosidase and fructose

There was a significant difference in SP-leptin levels between positive and negative SSR groups, and the cut-off value was 2.9 ng/mL (sensitivity of 43.1% and specificity of 75.0%) to predict SSR at TESE with 59% accuracy. Combined leptin and other markers can significantly improve the prediction accuracy of sperm retrieval in NOA patients. There were no significant differences in terms of seminal α-glucosidase and fructose between TESE (+) and TESE (−) patients.

China

2011

Aslani et al. [19]

21 NOA men with TESE (+) and 89 NOA men with TESE (-).

PRM1, PRM2, AKAP4, and DAZ

Comparison of the biomarkers and TESE (+) results did not show any significant correlation. But the presence of germ cell-specific DAZ and PRM2 transcripts in the semen of NOA patients can be used as specific noninvasive markers to predict the presence of mature spermatids and/or sperm in the testis.

Germany

2013

Freour

et al. [20]

20 NOA men with TESE (+) and 20 NOA men with TESE (-).

LGALS3BP

Seminal LGALS3BP expression was found to be significantly higher in TESE (+) men.

France

2014

Pansa

et al. [21]

20 NOA men with TESE (+) and 16 NOA men with TESE (-);24 NOA men with micro-TESE (+) and 18 NOA men with micro-TESE (-).

ESX1

ESX1 mRNA expression in the testis was strongly correlated with TESE (+) and micro-TESE (+).

Italy

2016

Fukuda

et al. [22]

9 NOA men with micro-TESE (+) and 19 NOA men with micro-TESE (-).

clusterin

There were no significant differences in terms of clusterin between micro-TESE (+) and micro-TESE (−) patients. However, univariate analysis identified seminal clusterin level as significant predictors of SSR by micro-TESE.

Japan

2017

Korbakiset al. [23]

15 NOA men with TESE (+) and 11 NOA men with TESE (-)

TEX101

A cut-off value of ≥ 0.6 ng/mL provided 73% sensitivity at 64% specificity for predicting sperm or spermatid retrieval in patients with NOA by TESE.

Canada

2017

Gilany

et al. [24]

9 NOA men with TESE (+) and 11 NOA men with TESE (-)

metabolites

Thirty-six differentiating metabolites were identified as prognostic biomarkers for TESE (−) and TESE (+) men.

Iran

2018

Gilany et al. [25]

10 NOA men with TESE (+) and 10 NOA men with TESE (-).

metabolic fingerprinting

Metabolic fingerprint, particularly oxidative status, significantly differed between TESE (+) and TESE (−) patients.

Iran

2018

Barceló

et al. [26]

8 NOA men with TESE (+) and 4 NOA men with TESE (-).

microRNAs

No significant differences between TESE (+) and TESE (−) were found regarding the individual levels of the eight miRNAs and the piRNA in SP exosomes. However, when the multivariate regression analysis was performed, it resulted in a model that included the miR-539-5p and the miR-941 expression values.

Spain

2020

Hashemi

et al. [27]

8 NOA men with micro-TESE (+) and 11 NOA men with micro-TESE (-)

ESX1, ZMYND15, TNP1 and PRM1

No significant differences between micro-TESE (−) and micro-TESE (+) were found regarding the level of ESX1 and ZMYND15. However, the expression level of TNP1 and PRM1 was significantly decreased in the sample with micro-TESE (−) versus micro-TESE (+).

Iran

2020

Xie et al. [28]

64 NOA men with micro-TESE(+) and 32 NOA men with micro-TESE(-)

long noncoding RNAs

A biomarker panel of lncRNAs (LOC100505685, SPATA42, CCDC37-DT, GABRG3-AS1, LOC440934, LOC101929088 (XR_927561.2),LOC101929088 (XR_001745218.1), LINC00343 and LINC00301)was constructed and verified in 64 NOA patients with micro-TESE (+) and 32 NOA patients with micro-TESE (−). When the decision-making process score exceeds 0.532 (cut-off value), the predictive accuracy of our panel reaches 95.238%, and the sperm retrieval surgery is recommended.

China

2021

Ji etal. [29]

20 NOA men with micro-TESE(+) and 32 NOA men with micro-TESE(-)

circRNAs

circRNAs (hsa_circ_0000277, hsa_circ_0060394 and hsa_circ_0007773) significantly differed between micro-TESE (+) and micro-TESE (−) patients.

China

2022

Zhang

et al. [30]

53 NOA men with micro-TESE(+) and 23 NOA men with micro-TESE(-).

microRNAs

A biomarker panel of microRNAs (hsa-miR-34b-3p, hsa-miR-34c-3p, hsa-miR-3065-3p, and hsa-miR-4446-3p) was constructed and tested in 53 NOA patients with micro-TESE (+) and 23 NOA patients with micro-TESE (−). The predictive model provided a high predictive accuracy (AUC = 0.927).

China

2022

Han et al. [31]

18 NOA men with micro-TESE(+) and 23 NOA men with micro-TESE(-).

tsRNAs

The extracellular vesicle tRF-Val-AAC-010 resulted in high predictive ability (AUC = 0.89, sensitivity = 72%, specificity = 91%, P < 0.0001) for predicting the presence of sperm in nonobstructive azoospermia undergoing micro-TESE.

China

  1. (+), successful; (-), unsuccessful; AMH Anti-Mullerian hormone, INHB Inhibin B, NOA Non-obstructive azoospermia, NAG neutral alpha glucosidase, PRM1 Protamine 1, PRM2 Protamine 2, AKAP4 A-kinase anchoring protein-4, DAZ Deleted in azoospermia, LGALS3BP Lectin galactoside-binding, soluble 3 binding protein, ESX1 Extra-embryonic tissue-spermatogenesis-homeobox gene 1, TEX101 Testis expressed gene 101, TNP1 Transition Protein 1, ZMYND15 Zinc Finger MYND Domain-Containing Protein 15