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, 37 (3), 296-312

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Ashok Agarwal  1   2 Neel Parekh  3 Manesh Kumar Panner Selvam  1   3 Ralf Henkel  1   4 Rupin Shah  5 Sheryl T Homa  6 Ranjith Ramasamy  7 Edmund Ko  8 Kelton Tremellen  9 Sandro Esteves  10   11 Ahmad Majzoub  1   12 Juan G Alvarez  13 David K Gardner  14 Channa N Jayasena  15   16 Jonathan W Ramsay  16 Chak Lam Cho  17 Ramadan Saleh  18 Denny Sakkas  19 James M Hotaling  20 Scott D Lundy  3 Sarah Vij  3 Joel Marmar  21 Jaime Gosalvez  22 Edmund Sabanegh  3 Hyun Jun Park  23   24 Armand Zini  25 Parviz Kavoussi  26 Sava Micic  27 Ryan Smith  28 Gian Maria Busetto  29 Mustafa Emre Bakırcıoğlu  30 Gerhard Haidl  31 Giancarlo Balercia  32 Nicolás Garrido Puchalt  33 Moncef Ben-Khalifa  34 Nicholas Tadros  35 Jackson Kirkman-Browne  36   37 Sergey Moskovtsev  38 Xuefeng Huang  39 Edson Borges  40 Daniel Franken  41 Natan Bar-Chama  42 Yoshiharu Morimoto  43 Kazuhisa Tomita  43 Vasan Satya Srini  44 Willem Ombelet  45   46 Elisabetta Baldi  47 Monica Muratori  48 Yasushi Yumura  49 Sandro La Vignera  50 Raghavender Kosgi  51 Marlon P Martinez  52 Donald P Evenson  53 Daniel Suslik Zylbersztejn  54 Matheus Roque  55 Marcello Cocuzza  56 Marcelo Vieira  57   58 Assaf Ben-Meir  59 Raoul Orvieto  60   61 Eliahu Levitas  62 Amir Wiser  63   64 Mohamed Arafa  65 Vineet Malhotra  66 Sijo Joseph Parekattil  67   68 Haitham Elbardisi  65 Luiz Carvalho  69   70 Rima Dada  71 Christophe Sifer  72 Pankaj Talwar  73 Ahmet Gudeloglu  74 Ahmed M A Mahmoud  75 Khaled Terras  76 Chadi Yazbeck  77 Bojanic Nebojsa  78 Damayanthi Durairajanayagam  79 Ajina Mounir  80 Linda G Kahn  81 Saradha Baskaran  1 Rishma Dhillon Pai  82 Donatella Paoli  83 Kristian Leisegang  84 Mohamed Reza Moein  85 Sonia Malik  86 Onder Yaman  87 Luna Samanta  88 Fouad Bayane  89 Sunil K Jindal  90 Muammer Kendirci  91 Baris Altay  92 Dragoljub Perovic  93 Avi Harlev  94

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Ashok Agarwal et al. World J Mens Health.


Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

Keywords: Infertility, male; MOSI; Oxidation reduction potential; Oxidative stress; Semen.

Conflict of interest statement

None of the authors declares competing financial interests. The authors do not have any potential interest in promoting MiOXSYS.


Fig. 1
Fig. 1. World map containing percentages of infertility cases per region that are due to male factor involvement among regions studied. Asia includes all of Russia. Data from Agarwal et al (Reprod Biol Endocrinol 2015;13:37) [10].
Fig. 2
Fig. 2. Conditions affecting male reproductive potential.
Fig. 3
Fig. 3. Worldwide incidence of MOSI in infertile men. aNational Institutes of Health (NIH) ( [61], Agarwal et al (2014) [60], Jarow et al (2011) [63].
Fig. 4
Fig. 4. (A) A receiver operating characteristic (ROC) curve was used to identify the oxidation-reduction potential (ORP) (mV/106 sperm/mL) cutoff that best predicted normal and abnormal semen parameters based on sensitivity (Sens), specificity (Spec), positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC). (B) Distribution of ORP in patients with at least one abnormal semen parameter versus patients with normal semen parameters, showing the established cutoff value of 1.34 mV/106 sperm/mL. Data from Agarwal et al (Asian J Androl 2019 [in press]) [59].
Fig. 5
Fig. 5. Distribution of oxidation-reduction potential (ORP) values in the infertile men with normal and abnormal semen parameters. (A) Data from Cleveland Clinic, Cleveland OH, USA (n=807); (B) Data from Hamad Medical Corporation, Doha, Qatar (n=3,966); (C) Data of asthenozoospermic patients from Hamad Medical Corporation, Doha, Qatar (n=3,966).
Fig. 6
Fig. 6. options for male oxidative stress infertility. OS: oxidative stress, ORP: oxidation-reduction potential, MiOXSYS: Male Infertility Oxidative System, MAGI: male accessory gland infection, MOSI: Male Oxidative Stress Infertility.

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