GLOBAL ANDROLOGY FORUM
GLOBAL ANDROLOGY FORUM
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Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility
Article #40: “Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility”
Authors: Ashok Agarwal, et al.
World J Men’s Health 2019 Sep 37(3): 296-312, Published online May 8, 2019,
DOI: 10.5534/wjmh.190055
CAPSULE
Contributors: Kadir Böcü, MD (Turkey), and
Germar M. Pinggera, MD (Austria)
Preamble:
Oxidative stress (OS) is increasingly recognized as a major factor in male infertility. Seminal reactive oxygen species (ROS), produced by leukocytes or abnormal and immature spermatozoa, play a key role in this process. While small amounts of ROS are necessary for normal sperm function, excessive levels can lead to OS and disrupt fertility by damaging sperm membranes and DNA and potentially causing disease in offspring. Recent studies indicate that 30% to 80% of infertile men have high seminal ROS levels, a condition that might be treatable.
There's a lack of consensus on how to best measure OS in clinical settings, leading to the proposal of "Male Oxidative Stress Infertility" (MOSI) as a term for infertile men with abnormal semen characteristics and OS. This category could include many previously classified as having idiopathic infertility. Epidemiological studies suggest that OS might affect about 56 million infertile men globally, with two-thirds potentially falling under the MOSI category. The impact of OS in men with normal semen in couples with unexplained infertility is less clear, though some evidence suggests a higher prevalence of leukocytospermia in this group.
Conventional semen analysis, used for over a century to assess sperm quality, is now recognized as insufficient for accurately predicting male fertility due to its limitations, such as poor reproducibility and subjective results.
The emergence of the term "Male Oxidative Stress Infertility (MOSI)" represents a significant leap forward in the understanding and categorization of male infertility issues. It recognizes the substantial role that oxidative stress plays in impairing male reproductive functions and the need for a specific terminology to describe cases that have hitherto been marked as idiopathic due to a lack of identifiable cause.
The challenge with idiopathic male infertility has always been the diagnosis and management in the absence of a clear-cut underlying pathology. By introducing MOSI as a definitive term, the medical community may now have a more concerted direction for investigation and treatment. The classification of MOSI acknowledges the complex interplay between reactive oxygen species (ROS) and spermatozoa, which can lead to DNA damage, poor sperm quality, and ultimately, reduced fertility.
This article by GAF authors on the management of MOSI provides a much-needed framework for clinicians. These guidelines can standardize the approach to diagnosis, including the assessment of oxidative stress levels, lifestyle factors, and potential environmental or occupational exposures that could contribute to elevated ROS. Furthermore, the inclusion of antioxidant therapy as a management strategy could offer new avenues for treatment, especially in cases where traditional interventions have proven inadequate.
From a personal standpoint, this article serves a crucial function in the paradigm shift of observing and managing male reproductive health. The formulation of the term MOSI itself showcases an innovative approach to a condition that exists in swathes of the infertile male populace. In addition, the authors' advocacy for the implementation of oxidation-reduction potential (ORP) as a diagnostic modality shines light on the growing importance of biochemistry and reproductive toxicity in fertility studies.
Agarwal et al.'s efforts to underscore the adoption of ORP measurement techniques such as the MiOXSYS system to quantify seminal oxidative stress are particularly impressive. The predilection of this research team towards evidence-based treatment aligns closely with our own philosophical bearings toward clinical intervention.
Key Takeaways:
- MOSI's introduction provides a more directed investigative and treatment approach.
- This practical guideline for MOSI may help to standardize diagnosis, integrate antioxidant therapy, and address interdisciplinary management.
- Recognition of the delicate balance in addressing oxidative stress versus antioxidant defense is vital for treatment efficacy.
- The proposed terminology and guidelines could potentially lead to precision management, reducing idiopathic cases and empowering both clinicians and patients.
- Success is contingent upon acceptance within the broader medical community and effective translation into clinical practice.
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Final Remarks:
In idiopathic male infertility, the diagnosis of MOSI serves as a key therapeutic target. Pinpointing oxidative stress allows for the effective implementation of antioxidant regimens, enhancing sperm quality and function. This strategy holds promise for improving ART success rates and enables the development of personalized treatment protocols for cases of unexplained infertility. MiOXSYS is a promising technology, however, its adoption as a diagnostic tool for seminal ORP is limited by cost, affecting its wider application in clinical practice. (Contributor: Ashok Agarwal)
My Personal Viewpoint on Male infertility in a MOSI setting
Dr. Kadir Böcü responds to the questions by Ashok Agarwal
Q1. What is your personal view on the significance of the MOSI diagnosis in the management of idiopathic male infertility?
Dr. Böcü: In my practice dealing with male infertility, I frequently come across cases where there's no clear explanation for the condition—termed idiopathic infertility. However, most of these cases are characterized by high levels of oxidative stress. High oxidative stress, a concept rooted in evidence-based medicine, usually affects the DNA within sperm and has been identified as a significant factor contributing to male infertility. I find that determining the imbalance between the body's creation of reactive oxygen species (ROS) and its ability to counteract these with antioxidants is crucial in tailoring treatment for individuals.
Examining MOSI from a standpoint rooted in evidence-based medicine is quite revealing when addressing idiopathic male infertility. Evaluating the oxidative stress in these patients could uncover previously hidden issues, offering new directions for their treatment.
Q2. What are the three main causes for the diagnosis of MOSI in your patients?
Dr. Böcü: The main causes for the diagnosis of MOSI in my patients generally include:
- Lifestyle factors such as smoking, excessive alcohol intake, and poor diet can increase oxidative stress.
- Environmental toxins and exposure to pollutants enhance ROS production.
- Varicoceles may impair scrotal thermoregulation and lead to a local increase in oxidative stress.
Q3. How do you diagnose patients with MOSI, and what are the three treatment choices (not including ART) that you offer to these patients in your practice?
Dr. Böcü: I can diagnose MOSI at a rate of 40-50% in my patients with idiopathic male infertility based on their oxidation-reduction potential (ORP) values.
For these patients with idiopathic male infertility where female factors and oxidative stress status are not present or unknown, I generally recommend three treatment choices that might include:
A. Lifestyle modifications: These include weight management, cessation of smoking, and limitation of alcohol intake, adopted as these changes can improve overall sperm quality.
B. Antioxidant therapy: Empirical use of antioxidants like vitamins E and C, Coenzyme Q10, or selenium might help reduce oxidative stress. Although commonly advised, recent studies suggest that indiscriminate use may not always be beneficial and should be personalized.
C. Varicocele repair: If a varicocele is present, surgical repair could potentially improve semen parameters and reduce oxidative stress.
On the other hand, in another group of idiopathic male infertility patients with normal ORP levels, I prefer off-label empirical hormonal treatment regimens aimed at inducing spermatogenesis, although the current literature is controversial.
Kadir Böcü, MD: Short Biography
Kadir Böcü, MD, FEBU
Assistant Professor in Urology
Niğde Ömer Halisdemir University Faculty of Medicine
Department of Urology, Niğde, Turkey
E-mail: drkadirbocu@gmail.com
ORCID ID: 0000-0003-4323-4037
Dr. Kadir Böcü
Dr. Kadir Böcü is a urologist with a focus on sexual medicine and men's health. He graduated from Necmettin Erbakan University School of Medicine in 2013 and completed his urology residency at Selcuk University School of Medicine in 2021. A member of the National Association of Urological Surgery since 2020. Dr. Böcü is active in the European Urology Association and has contributed significantly to the field through 13 articles, and numerous presentations at national and international forums. Currently, he is the leader of Research Team 13 in GAF.
My Personal Viewpoint on Male infertility in a MOSI setting
Dr. Germar M. Pinggera responds to the questions by Ashok Agarwal
1. What is your personal view on the significance of the MOSI diagnosis in the management of idiopathic male infertility?
Dr. Pinggera: As oxidative stress has been demonstrated to play a pivotal role in the etiology of male fertility, the introduction of the novel term MOSI represents a promising avenue. It offers the potential for clinicians to make more accurate diagnoses and treatments and for scientists to develop a structured foundation for a deeper understanding of the disease, facilitating comparable studies in the future.
2. Do you diagnose patients with MOSI (idiopathic + high OS) in your practice? If yes, then how do you treat them?
Dr. Pinggera: While classical microscopic semen analysis serves as an initial step in assessing male fertility status, it is essential to emphasize that it primarily adopts a descriptive approach, not comprehensively covering all aspects of male infertility. For numerous patients, supplementing semen analysis with the assessment of Male Oxidative Stress Infertility (MOSI) can significantly enhance diagnostic accuracy. Our experience suggests that the inclusion of MOSI evaluation provides a more discriminating tool for cases of unexplained male infertility.
In instances of elevated MOSI levels, the conventional empirical and somewhat off-label medical treatments for idiopathic male infertility, such as Selective Estrogen Receptor (SER) or hormonal therapies, may benefit from augmentation with antioxidative therapy over a span of several months.
3. What are the three main causes for the diagnosis of MOSI in your patients?
Dr. Pinggera: MOSI is indeed a critical issue in the realm of male reproductive health.
a. Oxidative Stress: OS occurs when there is an imbalance between reactive oxygen species (ROS) and the body's ability to detoxify them. High levels of ROS can damage sperm cells and affect their motility and DNA integrity, potentially leading to infertility. Various factors such as environmental toxins, smoking, and certain medical conditions can increase oxidative stress in the male reproductive system.
b. Antioxidant Deficiency: Antioxidants play a crucial role in neutralizing ROS and protecting sperm from oxidative damage. Inadequate intake of antioxidants through diet or lifestyle factors may lead to a deficiency, contributing to MOSI. Vitamin C, vitamin E, zinc, and selenium are examples of antioxidants that are important for male fertility.
c. Lifestyle and Environmental Factors: Modern lifestyles can also impact male fertility. Factors such as excessive alcohol consumption, smoking, exposure to environmental toxins (like pesticides or heavy metals), and sedentary habits can contribute to MOSI. Additionally, chronic stress and obesity may also have detrimental effects on sperm quality and fertility.
4. What are the three treatment choices (not including ART) that you will offer to patients with idiopathic male infertility (poor semen quality, no female factor, unknown OS status)?
Dr. Pinggera: When addressing idiopathic male infertility characterized by poor semen quality, no identified female factor, and unknown oxidative stress (OS) status, several treatment options could be considered, always, depending on the specific patient history and after addressing any underlying medical conditions that may contribute to his infertility. But, in general, to support any treatment options and to increase his therapeutic adherence, the knowledge of MOSI appears fundamental. Such patients can profit from lifestyle modifications and specific counselling like diet and nutritional optimization by adopting a balanced diet rich in antioxidants, vitamins, and minerals that support sperm health. In adipose men or those with primarily sedentary lifestyles exercise and weight management should be encouraged. Notwithstanding, smoking or alcohol abuse must be recommended before only advising for any pharmacological interventions by prescribing antioxidant supplements in mono or combination therapy.
Germar M. Pinggera, MD: Short Biography
Germar M. Pinggera, MD, LLM
Department of Urology
Innsbruck Medical University
Anichstrasse 35
6020- Innsbruck
Austria
Email: urologie.pinggera@gmail.com
ORCID id: 0000-0001-6463-2494
Dr. Germar-M. Pinggera is a renowned urologist and andrologist with a focus on men’s sexual health and male infertility as well urethral reconstructive surgery. He serves as the head of the Andrology & Male Infertility Unit in the department of Urology of the Medical University Innsbruck, Austria. He is certified as a Fellow of the European Committee of Sexual Medicine (FECSM). Dr. Pinggera also leads the Working Group of Andrology and Sexual Health for the Austrian Society of Urology and is since many years board member of the Austrian Endocrinologic Society (ÖGES). His expertise extends to being a reviewer for multiple international urological journals and organizing scientific congresses. He is involved in conducting clinical and scientific research as the principal investigator of several academic studies to discover novel therapeutic approaches. Dr. Pinggera's commitment to his field is further evidenced by his position as a full academician at the European Academy of Andrology (EAA). He is a senior member of the Global Andrology Forum (GAF) and serves as the Assistant Chairman on the GAFs Senior Advisory Board.