World J Mens Health.  2019 Sep;37(3):296-312. 10.5534/wjmh.190055.

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

Affiliations
  • 1American Center for Reproductive Medicine, Cleveland Clinic, OH, USA. agarwaa@ccf.org
  • 2Department of Urology, Cleveland Clinic, Cleveland, OH, USA.
  • 3Department of Medical Bioscience, University of the Western Cape, Cape Town, South Africa.
  • 4Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India.
  • 5School of Biosciences, University of Kent, Canterbury, UK.
  • 6Department of Urology, University of Miami, Miami, FL, USA.
  • 7Department of Urology, Loma Linda University Health, Loma Linda, CA, USA.
  • 8Department of Obstetrics Gynaecology and Reproductive Medicine, Flinders University, Bedford Park, Australia.
  • 9Division of Urology, Department of Surgery, University of Campinas (UNICAMP), Campinas, Brazil.
  • 10Faculty of Health, Aarhus University, Aarhus, Denmark.
  • 11Department of Urology, Hamad Medical Corporation and Weill Cornell Medicine-Qatar, Doha, Qatar.
  • 12Centro Androgen, La Coruña, Spain and Harvard Medical School, Boston, MA, USA.
  • 13School of BioSciences, University of Melbourne, Parkville, Australia.
  • 14Section of Investigative Medicine, Imperial College London, UK.
  • 15Department of Andrology, Hammersmith Hospital, London, UK.
  • 16Department of Surgery, Union Hospital, Shatin, Hong Kong.
  • 17Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt.
  • 18Boston IVF, Waltham, MA, USA.
  • 19Department of Urology, University of Utah, Salt Lake City, UT, USA.
  • 20Cooper University Hospital, Camden, NJ, USA.
  • 21Departamento de Biología, Universidad Autónoma de Madrid, Madrid, Spain.
  • 22Department of Urology, Pusan National University School of Medicine, Busan, Korea.
  • 23Medical Research Institute of Pusan National University Hospital, Busan, Korea.
  • 24Department of Surgery, McGill University, Montreal, QC, Canada.
  • 25Austin Fertility & Reproductive Medicine/Westlake IVF, Austin, TX, USA.
  • 26Uromedica Polyclinic, Kneza Milosa, Belgrade, Serbia.
  • 27Department of Urology, University of Virginia, Charlottesville, VA, USA.
  • 28Sapienza University of Rome, Rome, Italy.
  • 29Istanbul Florence Nightingale Hospital, Istanbul, Turkey.
  • 30Department of Dermatology, University Hospital Bonn, Bonn, Germany.
  • 31Division of Endocrinology, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Umberto I Hospital, Ancona, Italy.
  • 32IVI Foundation Edificio Biopolo - Instituto de Investigación Sanitaria la Fe, Valencia, Spain.
  • 33University Hospital, School of Médicine and PERITOX Laboratory, Amiens, France.
  • 34Division of Urology, Southern Illinois University School of Medicine, Springfield, IL, USA.
  • 35Centre for Human Reproductive Science, IMSR, College of Medical & Dental Sciences, The University of Birmingham Edgbaston, UK.
  • 36The Birmingham Women's Fertility Centre, Birmingham Women's and Children's NHS Foundation Trust, Mindelsohn Drive, Edgbaston, UK.
  • 37Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada.
  • 38Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 39Fertility Medical Group, São Paulo, Brazil.
  • 40Department of Obstetrics & Gynecology, Andrology Unit Faculties of Health Sciences, Tygerberg Hospital, Tygerberg, South Africa.
  • 41Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 42IVF Japan Group, Horac Grand Front Osaka Clinic, Osaka, Japan.
  • 43Manipal Fertility, Bangalore, India.
  • 44Genk Institute for Fertility Technology, Genk, Belgium.
  • 45Hasselt University, Biomedical Research Institute, Diepenbeek, Belgium.
  • 46Department of Experimental and Clinical Medicine, Center of Excellence DeNothe, University of Florence, Italy.
  • 47Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, Unit of Sexual Medicine and Andrology, Center of Excellence DeNothe, University of Florence, Florence, Italy.
  • 48Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan.
  • 49Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
  • 50Androbest Andrology & Urology Center, Hyderabad, India.
  • 51Section of Urology, University of Santo Tomas Hospital, Manila, Philippines.
  • 52SCSA Diagnostics, Brookings, SD, USA.
  • 53Fleury Group and Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • 54Origen, Center for Reproductive Medicine, Rio de Janeiro, Brazil.
  • 55Department of Urology, University of São Paulo (USP), Brazil.
  • 56Division of Urology, Infertility Center ALFA, São Paulo, Brazil.
  • 57Head of Male Infertility Division, Andrology Department, Brazilian Society of Urology, Rio de Janeiro, Brazil.
  • 58Fertility and IVF Unit, Department of Obstetrics and Gynecology, Hebrew-University Hadassah Medical Center, Jerusalem, Israel.
  • 59Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center (Tel Hashomer), Ramat Gan, Israel.
  • 60Tarnesby-Tarnowski Chair for Family Planning and Fertility Regulation, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
  • 61Soroka University Medical Center, Ben-Gurion University of the Negev Beer-Sheva, Beersheba, Israel.
  • 62IVF Unit, Meir Medical Center, Kfar Sava, Israel.
  • 63Sackler Medicine School, Tel Aviv University, Tel Aviv, Israel.
  • 64Department of Urology, Hamad Medical Corporation, Doha, Qatar.
  • 65Department of Andrology and Urology, Diyos Hospital, New Delhi, India.
  • 66PUR Clinic, South Lake Hospital, Clermont, FL, USA.
  • 67University of Central Florida, Orlando, FL, USA.
  • 68Baby Center, Institute for Reproductive Medicine, São Paulo, Brazil.
  • 69College Institute of Clinical Research and Teaching Development, São Paulo, Brazil.
  • 70Lab for Molecular Reproduction and Genetics, Anatomy, All India Institute of Medical Sciences, New Delhi, India.
  • 71Department of Reproductive Biology, Hôpitaux Universitaires Paris Seine Saint-Denis, Bondy, France.
  • 72Department of Reproductive Medicine and Embryology, Manipal Hospital, New Delhi, India.
  • 73Department of Urology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
  • 74Department of Endocrinology/ Andrology, University Hospital Ghent, Ghent, Belgium.
  • 75Department of Reproductive Medicine, Hannibal International Clinic, Tunis, Tunisia.
  • 76Department of Obstetrics, Gynecology and Reproductive Medicine, Pierre Cherest and Hartman Clinics, Paris, France.
  • 77Clinic of Urology, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
  • 78Department of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Selangor, Malaysia.
  • 79Department of Embryology, Faculty of Medicine, University of Sousse, Sousse, Tunisia.
  • 80Department of Pediatrics, New York University School of Medicine, New York, NY, USA.
  • 81Department of Obstetrics and Gynaecology, Lilavati Hospital and Research Centre, Mumbai, India.
  • 82Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
  • 83School of Natural Medicine, University of the Western Cape, Cape Town, South Africa.
  • 84Department of Andrology, Shahid Sadoughi Medical University, Yazd, Iran.
  • 85Southend Fertility & IVF, Delhi, India.
  • 86Department of Urology, School of Medicine, University of Ankara, Ankara, Turkey.
  • 87Redox Biology Laboratory, Department of Zoology and Center of Excellence in Environment and Public Health, Ravenshaw University, Cutrack, India.
  • 88Marrakech Fertility Institute, Marrakech, Morocco.
  • 89Jindal Hospital, Meerut, India.
  • 90Department of Urology, Istinye University Faculty of Medicine, Liv Hospital Ulus, Istanbul, Turkey.
  • 91Department of Urology, Ege University School of Medicine, Ä°zmir, Turkey.
  • 92Center of Urology, CODRA Hospital, Podgorica, Montenegro.
  • 93Fertility and IVF Unit, Soroka University Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel.

Abstract

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.

Keyword

Infertility, male; MOSI; Oxidation reduction potential; Oxidative stress; Semen

MeSH Terms

Antioxidants
Classification
Clinical Protocols
Diagnosis
DNA
Embryonic Structures
Female
Fertility
Health Expenditures
Humans
Infertility*
Infertility, Male*
Male*
Membranes
Ovum
Oxidants
Oxidation-Reduction
Oxidative Stress*
Reactive Oxygen Species
Reducing Agents
Reproductive Health
Semen
Spermatozoa
Subject Headings
Antioxidants
DNA
Oxidants
Reactive Oxygen Species
Reducing Agents

Figure

  • 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 Conditions affecting male reproductive potential.

  • Fig. 3 Worldwide incidence of MOSI in infertile men. aNational Institutes of Health (NIH) (https://www.nichd.nih.gov/health/topics/menshealth/conditioninfo/infertility) [61], Agarwal et al (2014) [60], Jarow et al (2011) [63].

  • 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 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 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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