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ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 4  |  Page : 1697-1702

Ischemia-modified albumin as a predicting biomarker of oxidative stress in males with primary infertility


1 Department of Dermatology and Andrology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission22-Aug-2022
Date of Decision17-Sep-2022
Date of Acceptance28-Sep-2022
Date of Web Publication04-Mar-2023

Correspondence Address:
Hanan A Derbala
Shebin Elkom, Menoufia Governorate
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_283_22

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  Abstract 


Objectives
To evaluate the serum ischemia-modified albumin (IMA) level in patients with primary infertility as a useful marker for assessing oxidative stress.
Background
Infertility is a condition affecting 15% of the world's population. IMA is calculated through the evaluation of the binding of cobalt to albumin.
Patients and methods
This prospective study was conducted on 40 male patients of primary infertility with completely normal partner and 40 apparently healthy volunteers as a control group. Every participant was subjected to laboratory tests (complete blood count, liver and renal functions, hemoglobin A1c, measurement of serum IMA by enzyme-linked immunosorbent assay, and semen analysis) and scrotal ultrasound.
Results
IMA was significantly higher in the case group compared with the control group (P < 0.001). Sperm count per milliliter was significantly lower in the case group compared with the control group (P < 0.001). Red blood cell count was significantly higher in the case group compared with the control group (P = 0.002), whereas white blood cell count was significantly lower in the case group compared with the control group (P = 0.001).
Conclusion
Both RBC count and IMA were significantly higher in cases compared with the control group. IMA may be a good predictor for patients with oligozoospermia due to reactive oxygen species injury.

Keywords: biomarker, ischemia-modified albumin, males, oxidative stress, primary infertility


How to cite this article:
Shoeib MA, Hassan RA, Bayomy NR, Derbala HA. Ischemia-modified albumin as a predicting biomarker of oxidative stress in males with primary infertility. Menoufia Med J 2022;35:1697-702

How to cite this URL:
Shoeib MA, Hassan RA, Bayomy NR, Derbala HA. Ischemia-modified albumin as a predicting biomarker of oxidative stress in males with primary infertility. Menoufia Med J [serial online] 2022 [cited 2024 Mar 28];35:1697-702. Available from: http://www.mmj.eg.net/text.asp?2022/35/4/1697/371014




  Introduction Top


Infertility is a condition affecting 15% of the world's population. It is a multifactorial phenomenon. Both males and females are implicated in the cause. Males contribute to 45–50% of these infertility cases [1]. The male factor is considered to be involved when one or more semen parameters are abnormal. These semen parameters include sperm concentration, motility, and/or morphology. Abnormalities in concentration is termed as oligozoospermia [2].

Abnormalities in semen parameters can occur owing to age, chromosomal abnormalities, hormonal imbalance, or infection and are often idiopathic. In the past, studies have attempted to delineate a relationship between male infertility and sperm quality as well as semen parameter abnormalities. Recently, studies have also drawn relationships between reactive oxygen species (ROS) and male infertility [3],[4],[5].

A few studies have performed small comparisons between oligozoospermic and nonoligozoospermic groups in terms of oxidative stress. These studies showed a negative correlation between hydrogen peroxide and nitric oxide and sperm count and motility. Furthermore, hydrogen peroxide was shown to be increased in groups of oligozoospermia [6].

Ischemia-modified albumin (IMA), calculated through the evaluation of the binding of cobalt to albumin, is a new biomarker for ischemia. A level of IMA is also detected in diseases related to oxidative stress, such as psoriasis, vascular injury of diabetes mellitus, multiple sclerosis, some cancers, acute appendicitis, polycystic ovary syndrome, and beta-thalassemia major. However, IMA has not yet been evaluated in infertility [7]. Our aim was to evaluate the serum IMA level in patients with primary infertility as a useful marker for assessing oxidative stress.


  Patients and methods Top


This prospective study was conducted on 40 male patients of primary infertility with completely normal partner and 40 apparently healthy volunteers as a control group.

A written consent was taken from patients and controls according to their rights and ethical committee, Faculty of Medicine, Menoufia University.

Inclusion criteria were male patients of primary infertility with completely normal partners.

Exclusion criteria were patients with hereditary, congenital, and obstructive causes of infertility; systemic diseases, for example, liver or kidney or heart diseases or diabetes mellitus or autoimmune diseases; obese patients; those who received drugs such as diuretics; or those who underwent hormone replacement therapy.

Cases of infertility were diagnosed by measurement of serum IMA by enzyme-linked immunosorbent assay (ELISA) and semen analysis, as well as scrotal ultrasound.

Every participant was subjected to complete history taking, general and local andrological examination, laboratory tests (complete blood count, liver enzymes, renal function, and hemoglobin A1c), measurement of serum IMA by ELISA and semen analysis, and scrotal ultrasound.

Patients fasted for at least 12 h. Blood samples were taken, and after 30 min, they were centrifuged at 4°C (1000 rpm, 15 min). The serum was stored at −80°C for no longer than 3 months. Moreover, all patients were subjected to laboratory investigation, including complete blood count (Sysmex xn 1000, Bornbarch 1, 22848 Norderstedt, Germany, and Kobe HQ Japan, Wakihama Park, 5 Chome-1-11 Iwaya Kitamachi, Nada-ku) and liver enzymes, renal function, and hemoglobin A1c using Cobas 6000 (c501 module) (Roche, Sandhofer Str. 116, 68305 Mannheim, Germany).

IMA was assessed by ELISA.

Name of kits: human IMA ELISA Kit (Zhejiang Quark Biotechnology Company, Zhejiang, People's Republic of China).

Scrotal ultrasound:

Scrotal ultrasound was performed using linear high-frequency transducers (above 7 MHz). Broadband transducers with a frequency range of 6 up to 12 MHz or higher were preferred.

Technique

Scrotal ultrasound was preceded by a thorough medical history and palpation. Palpation was performed to assess testicular and epididymal size, symmetry, tenderness, as well as to examine the spermatic cords. In the case of suspected pedicle torsion, palpation should be performed in a standing position. The scrotum (together with its contents) should be elevated with a hand, which alleviates pain accompanying orchitis and epididymitis, and increases pain associated with testicular torsion.

Scrotal ultrasound was performed with the patient in a supine or standing position. A lignin roll placed on patient's thighs to support and elevate the scrotum can be used to allow for an assessment of all scrotal structures. A similar effect can be achieved with the patient crossing his legs. This prevents scrotal movement between the thighs and, consequently, its unreliable evaluation.

Ultrasound examination begins with an assessment of testicular parenchyma, symmetry, size, and echogenicity. Rotating ellipsoid measurement with a precise determination of testicular borders in a maximum longitudinal section can be used for testicular size assessment.

Three perpendicular measurements, that is, top-to-bottom, sagittal, and frontal dimensions, can also be used for testicular measurement.

Ultrasound transducer compression on the testes changes their shape and can lead to false measurements. Preferably, the maximum longitudinal epididymal section should be visualized with the parenchyma of the entire testis. Testicular volume measurement is important in adult patients receiving hormonal therapy following scrotal surgeries.

The evaluation of testicular parenchyma should be performed accurately, starting from the longitudinal sections, through cross-sections and intermediate sections.

Statistical analysis

Statistical analysis was done by SPSS v26 (IBM Inc., Chicago, Illinois, USA). Quantitative variables were presented as mean and SD and compared between the two groups using unpaired Student's t test. Linear correlation coefficient (r) was used for detection of correlation between two quantitative variables in one group. Receiver operating characteristic curve analysis evaluates the overall test performance (where the area under the curve >50% denotes acceptable performance and area about 100% is the best performance for the test). A two-tailed P value less than 0.05 was considered statistically significant.


  Results Top


The mean ± SD age was 34.23 ± 8.89 years in the case group and 32.78 ± 6.97 years in the control group. Age was insignificantly different between both groups. RBC count was significantly higher in the case group compared with the control group (P = 0.002), whereas white blood cell (WBC) count was significantly lower in the case group compared with the control group (P = 0.001). However, the remaining parameters such as hemoglobin, platelet, SGOT, SGPT, urea, and creatinine were insignificantly different between both groups [Table 1].
Table 1: Age, laboratory investigations, serum ischemia-modified albumin, and sperm count of the studied groups

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Regarding IMA, the mean ± SD was 56.85 ± 5.44 U/ml in the case group and 40.23 ± 4.5 U/ml in the control group. IMA was significantly higher in the case group compared with the control group (P < 0.001) [Table 1].

Regarding semen analysis, the mean ± SD sperm count was 7.56 ± 3.25 count/ml in the case group and 125.13 ± 30.33 count/ml in the control group. Sperm count per milliliter was significantly lower in the case group compared with the control group (P < 0.001) [Table 1].

IMA had a significant positive correlation with RBCs (r = 0.319, P = 0.004) and SGPT (r = 0.238, P = 0.034), whereas a significant negative correlation was detected with WBCs (r=−0.249, P = 0.026) and sperm count (r=−0.879, P < 0.001) [Table 2].
Table 2: Correlation between serum ischemia-modified albumin and different parameters in all the studied participants (n=80)

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Based on the results of receiver operating characteristic curve analysis, IMA is a significant predictor of oxidative stress (area under the curve = 1.00, P < 0.001). At a cutoff more than 45.72 U/ml, it gives 100% sensitivity, 100% specificity, 100% positive predictive value, and 100% negative predictive value [Table 3] and [Figure 1].
Table 3: Receiver operating characteristic curve analysis of ischemia-modified albumin as a predicting biomarker of oxidative stress in the studied participants (n=80)

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Figure 1: ROC curve of IMA as a predicting biomarker of oxidative stress in the studied participants. IMA, ischemia-modified albumin; ROC, receiver operating characteristic.

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  Discussion Top


Infertility causes substantial psychological and social distress and imposes a considerable economic burden on patients and health care systems [8].

IMA is a nonspecific marker for many diseases, which are tightly associated with ischemia and oxidative stress. Despite this marker's low specificity, the evaluation of its content may provide valuable information regarding the duration of diseases and possible complications, and it can be used in the differential diagnosis of certain pathological conditions [9].

The mean ± SD age was 34.23 ± 8.89 years in the case group and 32.78 ± 6.97 years in the control group. There was no statistically significant difference between case and control groups. There was a wide age range included in our study, which gives an accurate result about marker efficacy and its availability among different target groups.

In line with our results, Inal et al.[10] included 30 men with nonobstructive azoospermia (no spermatozoa in ejaculate), 30 men with oligospermia (total progressive motile sperm count <15 × 106/ml), and 33 fertile men with nomospermia (with at least one child, as the control group). The results showed that there was no statistically significant difference among the three groups (nonobstructive azoospermia, oligospermia, and normospermia).

In our study, according to laboratory investigations, RBC count was significantly higher in the case group compared with the control group, whereas WBC count was significantly lower in the case group compared with the control group. However, the remaining parameters, such as hemoglobin, platelet, SGOT, SGPT, urea, and creatinine, were insignificantly different between both groups.

In the present study, it was found that IMA was significantly higher in the case group compared with the control group.

Varicocele has been recognized as the leading cause of male infertility and can affect spermatogenesis and cause testicular and epididymal disorders through multiple diverse pathophysiological processes. Reactive oxygen species (ROS) produced by oxidative stress have been reconciled as an important pathogenic factor throughout the course of varicocele. Testis responds to heat stress, hypoxia, and inflammation at the cost of producing excessive ROS. High levels of ROS can lead to infertility not only through lipid peroxidation or DNA damage but also through inactivating enzymes and proteins in spermatogenesis; abnormal sperm morphology, DNA fragmentation, and protamine scarcity in men with varicocele were apparently higher than those infertile individuals [11].

Piwowar et al.[12] aimed to evaluate IMA in patients with type 2 diabetes mellitus and estimation of its connection with vascular complications, glycemic control, hypertension, dyslipidemia, and obesity, where about 76 diabetic patients and 25 controls were included in the study. The results showed that diabetic patients had significantly higher level of IMA in comparison with controls. Patients with poor glycemic control had higher IMA level in comparison with those with good glycemic control.

Depending on the pathogenesis of obesity, lipid oxidation is impaired, and a protein uncoupling oxidative phosphorylation in white fat cells is dysfunctional in these individuals. Oxidative stress biomarkers in body fluids and tissues can be used in the diagnosis, treatment, and follow-up of diseases in both research and the clinical setting. There are numerous oxidative stress-related biomarkers, but one of the most commonly used parameters is IMA [13].

Therefore, Ates et al.[14] conducted a cross-sectional study and compared plasma thiol/disulphide, IMA levels, and ferroxidase activity between the study groups. Participants were divided into three groups: group 1 consisted of 30 insulin-resistant women with obesity, group 2 consisted of 31 noninsulin-resistant women with obesity, and group 3 consisted of 34 overweight women. The results showed that IMA was lower in the noninsulin-resistant group than in the insulin-resistant group and overweight group.

Early stages of pregnancy are associated with oxidative stress existing between the maternal decidua and villus placenta. This state of hypoxia exists before the development of maternofetal circulation [15].

Hence, Bahinipati and Mohapatra [15] aimed to evaluate maternal serum IMA in normal pregnancy and correlate it with serum malondialdehyde, a known lipid peroxidation marker. Similarly, IMA/albumin was evaluated for correction of decrease in serum albumin in pregnancy and correlated with serum malondialdehyde, where 40 healthy normal pregnant women and 41 nonpregnant healthy controls were included in the study. The results showed that serum IMA and IMA/albumin were significantly higher in normal pregnant women (72.54 ± 9.89 U/l, 20.16 ± 3.94) compared with nonpregnant healthy controls (48.47 ± 8.30 U/l, 10.51 ± 1.76).

Furthermore, acute kidney injury (AKI) is a serious kidney disease carrying high morbidity and mortality. Many factors including ischemic reperfusion injury, inflammation, hypoxia, and oxidative stress play a central role in the physiopathology of AKI. Oxidative stress is defined as tilting the balance between antioxidant defense mechanisms and attacks of free radicals in favor of free radicals [16].

Mertoglu et al.[17] measured IMA and other biochemical and hematological parameters in serum of 39 patients with AKI and of 38 healthy controls. The results showed that IMA was significantly higher in patients with AKI compared with the control group.

Hypertension is one of the leading causes of morbidity and mortality worldwide. A prompt diagnosis and treatment of hypertensive retinopathy (HR), the leading complication of hypertension, is pivotal for a better visual outcome. Increased blood pressure on its own cannot fully clarify the development of retinal alterations; therefore, an additional pathogenetic mechanism, such as oxidative stress, might be inquired [18].

Pavlovschi et al.[18] evaluated the changes in the level of IMA in the serum and tears of patients with hypertensive retinopathy to establish the predictive value of IMA for the HR progression. Serum and tear samples for the measurement of IMA were collected from 90 patients detected primarily with HR, who were not taking any antihypertensive or other drug that could influence the results of the study. They were divided according to the Keith-Wagener classification into GI – 36 patients with HR grade I, GII – 35 with HR grade II, and GIII – 19 with HR grade III. The results showed that there was a statistically significant difference in serum IMA (P = 0.006), and the values increased in parallel with the progression of HR.

In the present study, it was found that sperm count per milliliter was significantly lower in the case group compared with the control group.

In line with our results, Dorostghoal et al.[19] screened semen specimens obtained from fertile volunteer donors (n = 105), with normal semen characteristics whose wives achieved a full-term pregnancy within the last 2 years, and from infertile men (n = 112). The results showed that sperm count per milliliter was significantly lower in the case group compared with the control group [60.0 (55.0–64.0) and 12.0 (8.0–45.0), respectively].

Moreover, Venkatesh et al.[20] conducted a pilot study where about 51 semen samples were collected. Approximately 33 primary infertile cases and 18 proven fertile controls were included to find the clinical significance of ROS levels in infertile Indian men. The results showed that that sperm count per milliliter was significantly lower in the case group compared with the control group.


  Conclusion Top


In patients with oligozoospermia, IMA was observed to be significantly higher in the case group compared with the control group. However, sperm count per milliliter was considerably lower than in patients with oligozoospermia. Owing to ROS injury, IMA may be a good predictor for patients with oligozoospermia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rowe PJ, Comhaire FH, Hargreave TB, Mahmoud AMA. World health manual for the standardized investigation, diagnosis and management of the infertile male. Geneva: World Health Organization; 2000.  Back to cited text no. 1
    
2.
Cavallini G. Male idiopathic oligoasthenoteratozoospermia. Asian J Androl 2006; 8:43–57.  Back to cited text no. 2
    
3.
Agarwal A, Makker K, Sharma R. Clinical relevance of oxidative stress in male factor infertility: an update. Am J Reprod Immunol 2008; 59:2–11.  Back to cited text no. 3
    
4.
Desai N, Sharma R, Makker K, Sabanegh E, Agarwal A. Physiologic and pathologic levels of reactive oxygen species in neat semen of infertile men. Fertil Steril 2009; 92:26–31.  Back to cited text no. 4
    
5.
Mahfouz R, Sharma R, Thiyagarajan A, Kale V, Gupta S, Sabanegh E, et al. Semen characteristics and sperm DNA fragmentation in infertile men with low and high levels of seminal reactive oxygen species. Fertil Steril 2010; 94:21–41.  Back to cited text no. 5
    
6.
Kullisaar T, Türk S, Kilk K, Ausmees K, Punab M, Mändar R. Increased levels of hydrogen peroxide and nitric oxide in male partners of infertile couples. Andrology 2013; 1:50–85.  Back to cited text no. 6
    
7.
Ataş H, Gönül M, Öztürk Y, Kavutçu M. Ischemic modified albumin as a new biomarker in predicting oxidative stress in alopecia areata. Turk J Med Sci 2019; 49:129–138.  Back to cited text no. 7
    
8.
Agarwal A, Baskaran S, Parekh N, Cho C-L, Henkel R, Vij S, et al. Male infertility. Lancet 2021; 397:319–333.  Back to cited text no. 8
    
9.
Krzystek-Korpacka M, Kempiński R, Bromke MA, Neubauer K. Oxidative stress markers in inflammatory bowel diseases: systematic review. Diagnostics 2020; 10:601.  Back to cited text no. 9
    
10.
Inal HA, Ozturk Inal Z, Mermer S, Aksoy E, Bayraktar AM, Can U. Investigation of serum vitamin D and ischaemia-modified albumin levels in infertile Turkish men. Andrologia 2020; 52:e13507.  Back to cited text no. 10
    
11.
Wang K, Gao Y, Wang C, Liang M, Liao Y, Hu K. Role of oxidative stress in varicocele. Front Genet 2022; 13:850114.  Back to cited text no. 11
    
12.
Piwowar A, Knapik-Kordecka M, Warwas M. Ischemia-modified albumin level in type 2 diabetes mellitus – preliminary report. Dis Markers 2008; 24:311–317.  Back to cited text no. 12
    
13.
Manna P, Jain SK. Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: causes and therapeutic strategies. Metab Syndr Relat Disord 2015; 13:423–444.  Back to cited text no. 13
    
14.
Ates E, Set T, Karahan SC, Biçer C, Erel Ö. Thiol/disulphide homeostasis, ischemia modified albumin, and ferroxidase as oxidative stress markers in women with obesity with insulin resistance. J Med Biochem 2019; 38:445.  Back to cited text no. 14
    
15.
Bahinipati J, Mohapatra PC. Ischemia modified albumin as a marker of oxidative stress in normal pregnancy. J Clin Diagn Res 2016; 10:BC15.  Back to cited text no. 15
    
16.
Rahbar Saadat Y, Hosseiniyan Khatibi SM, Ardalan M, Barzegari A, Zununi Vahed S. Molecular pathophysiology of acute kidney injury: the role of sirtuins and their interactions with other macromolecular players. J Cell Physiol 2021; 236:3257–3274.  Back to cited text no. 16
    
17.
Mertoglu C, Gunay M, Gurel A, Gungor M, Gul V. Ischemic modified albumin increases in acute kidney injury. Rev Rom Med Lab 2018; 26:37–43.  Back to cited text no. 17
    
18.
Pavlovschi E, Pantea V, Borovic D, Tagadiuc O. Study of ischemia modified albumin (IMA) as a biomarker in hypertensive retinopathy. Med Pharma Rep 2021; 94:185.  Back to cited text no. 18
    
19.
Dorostghoal M, Kazeminejad S, Shahbazian N, Pourmehdi M, Jabbari A. Oxidative stress status and sperm DNA fragmentation in fertile and infertile men. Andrologia 2017; 49:e12762.  Back to cited text no. 19
    
20.
Venkatesh S, Riyaz A, Shamsi M, Kumar R, Gupta N, Mittal S, et al. Clinical significance of reactive oxygen species in semen of infertile Indian men. Andrologia 2009; 41:251–256.  Back to cited text no. 20
    


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