1. The document discusses a lecture on medical therapy for male infertility given by Dr. Sandro Esteves in Dubai in 2012.
2. It outlines the use of specific therapies like hormones for conditions like hypogonadism, and non-specific empirical treatments. Oral antioxidants are discussed as a hot topic for improving fertility outcomes.
3. Obesity is identified as a risk factor for male infertility, and the use of aromatase inhibitors to increase sperm production by reducing estrogen levels in obese men is presented.
SPERM DNA FRAGMENTATION
Clinical threshold value of DNA Fragmentation Index is 30%, that means 70% are normal.
Has role in deciding to go for ICSI in patients who have high fragmentation
DIAGNOSTIC CATEGORIES
After evaluation we should be able to segregate the patients into different categories depending on cause and what treatment we can offer.
Broadly we have can segregate into categories:
Medical/ Surgical treatment
Will help
May Help or improve chances of success in ART
Will not help
MEDICAL AND SURGICAL
MANAGEMENT OF
MALE INFERTILITY
MEDICAL THERAPYSPECIFIC
Endocrine Disorders
Ejaculatory Disorders
Genital Tract
Infections
EMPIRICAL THERAPY
Treatments for Idiopathic Male infertility
AROMATASE INHIBITORS
Empirical antioxidant treatment
Vitamin C and E
Carotenoids and Lycopene
Folate
Carnitine and N-acetylcysteine
Selenium
Clomiphene citrate and aromatase inhibitors
Lifestyle complimentary treatments
Environmental exposure prevention
Obesity prevention
Coital Lubricants
Eastern approaches-Acupuncture
Pyospermia: evaluate the patient for sexually transmitted diseases, penile discharge, prostatitis, or epididymitis
Coital therapy
Immunologic infertility
Corticosteroid suppression, sperm washing, IUI, IVF, and ICSI.
COMPLIMENTARY TREATMENTS
Lifestyle complimentary treatments
Environmental exposure prevention
Obesity prevention
Coital Lubricants
Eastern approaches-Acupuncture
Nonsurgical treatments
Pyospermia: evaluate the patient for sexually transmitted diseases, penile discharge, prostatitis, or epididymitis
Coital therapy
Immunologic infertility
Corticosteroid suppression, sperm washing, IUI, IVF, and ICSI.
Ejaculatory Duct obstruction
PESA-Percutaneous Epididymal Sperm Aspiration
Micro-TESE : Testicular Sperm Extraction (involves a small incision and snipping off some tissue from inside the testicle.
Micro TESE- Surgical Approach
MANAGEMENT
The management of infertility should take place in a dedicated infertility clinic staffed by an appropriately trained professional team of Andrologists with facilities for investigating and managing problems in both partners.
SCI International Hospital
M-4, Greater Kailash-1, New Delhi-110048
www.scihospital.com
SPERM DNA FRAGMENTATION
Clinical threshold value of DNA Fragmentation Index is 30%, that means 70% are normal.
Has role in deciding to go for ICSI in patients who have high fragmentation
DIAGNOSTIC CATEGORIES
After evaluation we should be able to segregate the patients into different categories depending on cause and what treatment we can offer.
Broadly we have can segregate into categories:
Medical/ Surgical treatment
Will help
May Help or improve chances of success in ART
Will not help
MEDICAL AND SURGICAL
MANAGEMENT OF
MALE INFERTILITY
MEDICAL THERAPYSPECIFIC
Endocrine Disorders
Ejaculatory Disorders
Genital Tract
Infections
EMPIRICAL THERAPY
Treatments for Idiopathic Male infertility
AROMATASE INHIBITORS
Empirical antioxidant treatment
Vitamin C and E
Carotenoids and Lycopene
Folate
Carnitine and N-acetylcysteine
Selenium
Clomiphene citrate and aromatase inhibitors
Lifestyle complimentary treatments
Environmental exposure prevention
Obesity prevention
Coital Lubricants
Eastern approaches-Acupuncture
Pyospermia: evaluate the patient for sexually transmitted diseases, penile discharge, prostatitis, or epididymitis
Coital therapy
Immunologic infertility
Corticosteroid suppression, sperm washing, IUI, IVF, and ICSI.
COMPLIMENTARY TREATMENTS
Lifestyle complimentary treatments
Environmental exposure prevention
Obesity prevention
Coital Lubricants
Eastern approaches-Acupuncture
Nonsurgical treatments
Pyospermia: evaluate the patient for sexually transmitted diseases, penile discharge, prostatitis, or epididymitis
Coital therapy
Immunologic infertility
Corticosteroid suppression, sperm washing, IUI, IVF, and ICSI.
Ejaculatory Duct obstruction
PESA-Percutaneous Epididymal Sperm Aspiration
Micro-TESE : Testicular Sperm Extraction (involves a small incision and snipping off some tissue from inside the testicle.
Micro TESE- Surgical Approach
MANAGEMENT
The management of infertility should take place in a dedicated infertility clinic staffed by an appropriately trained professional team of Andrologists with facilities for investigating and managing problems in both partners.
SCI International Hospital
M-4, Greater Kailash-1, New Delhi-110048
www.scihospital.com
Patient selection and work-up
Ovarian stimulation
Monitoring of follicular growth and endometrial development
Timing of insemination
Number of inseminations
Semen preparation
Insemination procedure
Luteal support
Dr Sujoy Dasgupta moderated a Panel Discussion on "Difficult cases in IUI" in the Annual Conference of ISAR (Indian Society of Assisted Reproduction), Bengal held in December, 2022
Individualizing Ovarian Stimulation Protocols for IVFSherInstitute
Have you experienced poor response to IVF medications? Been told you had "Empty Follicle Syndrome?" Had lots of eggs retrieved but very few fertilized? Experienced Ovarian Hyperstimulation Syndrome? All of these issues can be tied to or affected by your protocol of stimulation. Dr. Geoffrey Sher presents his approach to customizing ovarian stimulation based on 30 years' experience in the IVF field. He outlines a number of his stimulation protocols and discusses the factors that can cause IVF failure due to improper stimulation protocols.
Patient selection and work-up
Ovarian stimulation
Monitoring of follicular growth and endometrial development
Timing of insemination
Number of inseminations
Semen preparation
Insemination procedure
Luteal support
Dr Sujoy Dasgupta moderated a Panel Discussion on "Difficult cases in IUI" in the Annual Conference of ISAR (Indian Society of Assisted Reproduction), Bengal held in December, 2022
Individualizing Ovarian Stimulation Protocols for IVFSherInstitute
Have you experienced poor response to IVF medications? Been told you had "Empty Follicle Syndrome?" Had lots of eggs retrieved but very few fertilized? Experienced Ovarian Hyperstimulation Syndrome? All of these issues can be tied to or affected by your protocol of stimulation. Dr. Geoffrey Sher presents his approach to customizing ovarian stimulation based on 30 years' experience in the IVF field. He outlines a number of his stimulation protocols and discusses the factors that can cause IVF failure due to improper stimulation protocols.
Physiology of Male Infertility | Seeds of InnocenceSOI Delhi
Male Infertility is a inability that causes pregnancy in a female fertile. Male infertility is commonly due to Low sperm Count. Soi provides best male infertility treatment in delhi, ghaziabad - India. Call us : 9810350512
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Rational Investigations and Management of Male InfertilitySujoy Dasgupta
Dr Sujoy Dasgupta delivered an invited lecture in the annual conference of WMOGS (West Midnapore Obstetric and Gynaecological Society) held on 16 September, 2023
Acquired Disorders of Spermatogenesis By Paul J. Turek MD, Emeritus Professor...The Turek Clinics
Lecture on Acquired Disorders of Spermatogenesis written and presented by Paul J. Turek MD, Emeritus Professor and Endowed Chair in Urology Education, Department of Urology, University of California San Francisco and current Director of the The Turek Clinic, in San Francisco, California.
Discuss the etiologies and the pathophysiology of erectile dysfunction (ED)
Describe the mechanism of action of agents used to treat ED
Recommend pharmacologic and non-pharmacologic treatment for ED
Identify drug interactions and adverse effects of currently used medications for ED
Identify treatment related side effects.
Points:
Male Sex Hormone - Androgens (Mainly Testosterone)
Synthesis, Regulation & metabolism (By both Hypothalamus & Pituitory gland)
Various Action/ Physiological roles over:
1. Sex organs and secondary sex characters (Androgenic)
2. Testes
3. Skeleton and skeletal muscles (Anabolic)
4. Erythropoiesis
Anabolic Steroids & their uses
Antiandrogens (Classification, MOA & Uses)
Drugs for erectile dysfunction (MOA & Uses)
Main Male Sex Hormone is Testosterone which converts into its highly active form i.e. dihydrotestosteron (DHT).
Main Female Sex Hormones are Estrogen & Progesterone.
IVF- How it changed the perspective of Male InfertilitySujoy Dasgupta
Dr Sujoy Dasgupta was invited to deliver a talk in a CME held on the World IVF Day (25 July, 2023) organized by Burdwan Obst Gynae Society and Corona Remedies.
Air quality: is it that important? And if so, how to measure and control it?Sandro Esteves
Quality and Risk Management in the IVF Laboratory; Redlara Brasil, Belo Horizonte, 14-15 September 2016
Content:
1.Air quality: is it that important?
2. How to control?
3. How to measure?
Novel concepts in male factor infertility: clinical and laboratory perspectivesSandro Esteves
Presentation Objectives:
1. Update on the WHO reference values for semen parameters, and understand the role of sperm DNA fragmentation testing to decision-making strategies;
2. Learn how to counsel azoospermic men seeking fertility, and the role of gonadotropin therapy in this infertility condition;
3. Understand the benefits of microsurgery to both sperm retrieval and varicocele treatment;
4. Appraise the role of medical and surgical interventions to infertile men undergoing ART.
Public lecture - Stem Cell and Male InfertilitySandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Public Lecture - Stem Cell and Male Infertility
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Evaluation of antidepressant activity of clitoris ternatea in animals
Advancements in the medical management of male infertility
1. EOFF 2012, Dubai, Nov 24th
Sandro Esteves, MD, PhD
Director, ANDROFERT
Center for Male Reproduction and Infertility
Campinas, BRAZIL
2. Learning Objectives
How to revert male hypogonadism and
infertility by specific medical therapy
Oral antioxidant therapy is a hot topic: what
you need to know in 2012
Obesity is a risk factor for male infertility: how
to use aromatase inhibitors to increase sperm
production
2
Esteves
3. Esteves, SC; EOFF 2012
Review this lecture at:
http://www.androfert.com.br/review
4. Medical Therapy for Male Infertility
Overview
Specific Non-specific
Therapy Therapy
Empirical
Genital tract treatment for
infection idiopathic male
infertility
Endocrine
disorders
Antioxidants Aromatase
inhibitors
Ejaculatory
disorders
4
Esteves
5. Medical Therapy for Male Infertility
Non-specific
Androgens Therapy
hCG/HMG
FSH Empirical
Anti-estrogens treatment for
idiopathic male
Bromocriptine infertility
Alpha-blockers
Systemic corticosteroids No demonstrable
cause for abnormal
semen parameters;
~44% infertile men
5
Esteves
6. Empirical Medical Treatment
for Idiopathic Male Infertility
In general, NOT
EFFECTIVE.
Selected cases
may benefit of FSH
and anti-estrogens
Guidelines on Male Infertility.
6 European Association of Urology 2012
Esteves
8. Adult onset hypo-hypo:
Medical therapy aimed to restore
spermatogenesis and
androgenic status
Classic Treatment:
Urinary hCG 1,000-2,000 UI IM injections; twice or t.i.w;
minimum 12 weeks
Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 Week 9 Week 10 Week 11 Week 12 Maintenance
8
Esteves
9. Adult onset Hypo-hypo:
hCG Preparations
LH activity Ampoule/ % Protein Source Technology Route of
(IU/ampule vial filling contamination administration
or vial) method
Urinary hCG 1,000- Filled-by- <5% Urine Chemical IM
10,000 bioassay extraction
Recombinant 250µg Filled-by- Negligible Transfected Recombinant SC
hCG mass CHO cells DNA
(FbM)
9
Esteves
10. Clinical Efficacy, Safety and Tolerability of Recombinant
hCG to Restore Spermatogenesis and Androgenic
Status of Hypogonadotropic Hypogonadism Males
Series of 11 azoospermic males with adult onset hypo-hypo
Pituitary tumor, Steroid abuse, Testosterone replacement therapy, Encephalic trauma
Once a week SC self-administration of 250µg rec-hCG (ready-to-use prefilled syringe)
Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 Week 9 Week 10 Week 11 Week 12 Evaluation
Restoration of spermatogenesis and androgen production: 10/11 men; No side-effects
Baseline Posttreatment
10
Esteves SC, Papanikolaou V; Fertil Steril 2011; Vol 96: S230
Esteves
11. Specific and Non-Specific Medical
Treatment of Male Infertility
1. There is little scientific
evidence for an empirical
medical treatment in idiopathic
male infertility.
2. Medical treatment is
recommended in cases of
Hypogonadotropic
Hypogonadism (GR-A) .
11
Esteves
12. Oxidative Stress
An emerging
explanation
30%-80% of infertile men have for several
elevated markers of OS
Agarwal et al., Urology 2006
cases of male
infertility
Seminal
Reactive Oxygen Species (ROS)
(Log ROS + 1; cpm)
2,5
2
1,5
1
0,5
0
Fertile Infertile
Pasqualotto et al., Fertil Steril 2000
12
Esteves
13. Reactive Oxygen Species (ROS)
Chemical species with unpaired
electron capable to oxidize lipids,
proteins and nucleic acids:
Superoxide anion (•O-2)
Hydroxyl radical (•OH)
Hydrogen peroxide (H2O2)
Peroxyl radical (ROO•)
Hypochlorite ion (OCl-)
Generated from aerobic metabolism in
mitochondria.
Sources:
Leukocytes (extrinsic)
Spermatozoa (intrinsic)
Sperm and Seminal Plasma Antioxidants:
Enzymatic (SOD, catalase, GPX): inactivate ROS (conversion into other substances)
Non-enzymatic (ascorbic acid, alpha-tocopherol, carnitine, etc.): neutralize ROS
13
Lampiao et al., Oxidative stress. In: Male Infertility. Parekattil & Agarwal (eds) 2012, pp.225-35
Esteves
14. Rationale for Oral
Antioxidants in Male
Infertility
AO classified according to
their mechanism of action:
Catalytic: enhances the
already present antioxidant
enzymes (Glutathione, NAC).
Scavenging:
Water soluble: react with
oxidants in the cytosol
(Vitamin C)
Lipid soluble: protect cell
membrane from lipid
peroxidation (Vitamin E)
14
Esteves
15. Oral Antioxidants
Cochrane Review 2011
Outcome N N Effect size
studies participants (OR; 95% CI)
Live birth 3 214 4.85 [1.92, 12.24]
Pregnancy rate 15 964 4.18 [2.65, 6.59]
DNA fragmentation 1 64 -13.80 [-17.50, -10.10]
Miscarriage, sperm 6-16 242-700 No effect
count, sperm motility
Adverse effects 6 426 No effect
Improve the outcomes of live birth and pregnancy rate for
subfertile couples undergoing ART cycles
15 Showell MG et al. Antioxidants for male subfertility.
Esteves Cochrane Database Syst Rev 2011 Jan 19;(1):CD007411.
16. Sperm DNA Fragmentation and
Assisted Conception
Live Birth Rates by Pregnancy by Method in Cases
Intrauterine Insemination of Elevated Sperm DNA
Fragmentation
42%
19%
P <0.05
26%
OR = 0.07
[95% CI: 0.01-0.48]
1.5%
Normal Elevated IVF ICSI
16 Adapted from Bungum et al., Hum Reprod 2007
Esteves
17. Sperm DNA Fragmentation and
Miscarriage
• Population: Meta-analysis of 16 cohort studies (2,969 couples),
14 prospective.
• Techniques for DNA integrity:
Acridine orange-based assays, TUNEL and COMET.
• Findings:
Significant increase in miscarriage rates in patients undergoing
IVF/ICSI with high sperm DNA damage compared with those
with low DNA damage.
Risk ratio (RR) = 2.16 (1.54, 3.03), P < 0.00001).
Miscarriage rates are positively correlated
with sperm DNA damage levels
17 Robinson L et al. Hum Reprod. 2012; 27(10): 2908-17
Esteves
18. Oral Antioxidant Therapy
Controversies
Methodological weakness of antioxidants
trials make it difficult to determine “who”,
“how” and “for how long”
• Patient selection and controls
• Associated pathology
• Single or combination antioxidants
• Dosage & formulation
• Outcome measures
• Varying duration of treatment
• Lack of diagnostic markers for oxidative stress
• Presence of molecular and genetic differences
18
Esteves
19. Oral Antioxidants
in Male Infertility
Beneficial No effect
Kodama 1997 Giovenco, 1987
Dawson, 1992 Moilanen, 1993
Kessopoulou, 1995 Iwanier, 1995 No consensus yet.
Vezina, 1996 Rolf, 1999
Vicari, 2001; 2002 Sigman, 2006 Short-term use
Lenzi, 2003; 2004 appear to be safe.
Cavallini, 2004
Comhaire, 2005 Detrimental Caution against
Grecco 2005
long-term use and indiscriminate use
Menezo 2007 high doses;
Tremellen 2007
of high dosages for
increased mortality in long periods.
Piomboni 2008 cancer population-
Gil Villa 2009 based studies.
Heinonen, 1994
Lonn, 2005
Bjelakovic, 2007
19
Esteves
20. Who are the candidates for Oral
Antioxidant Therapy?
Infertile men with OS
Diagnosis
Indirect Assessment
• Lipid Peroxidation (Malondialdehyde)
• Protein oxidation products (eg. 8-OHdG)
• Sperm DNA integrity
Direct Assessment
• Total Antioxidant Capacity
• Seminal ROS Levels
• Detection of Superoxide Anion
20 Esteves et al. What the gynecologist should know about male infertility:
Esteves an update. Arch Gynecol Obstet 2012; 286(1): 217-29
21. Quick and Easy Tests for OS
Sperm DNA Fragmentation Reactive Oxygen Species
Sperm Chromatin Detection of Superoxide
Dispersion Test: Anion:
● Sperm with absent “halos” ● Reduction of Nitroblue Tetrazolium
have DNA strand breaks in Formazan (coloured intermediate)
● Semen/Spermatozoa ● Semen
● Quantitative ● Qualitative
21
Esteves
22. How to use Antioxidant Therapy
Treatment Strategy
Once OS is diagnosed,
Differentiate between
focus on identifying Select antioxidant
sperm and leukocyte
and controlling source formulation and dosage
source of ROS
of increased ROS
Varicocele Ascorbic acid (Vit. C)
Testing for - tocopherol (Vit. E)
Genital Infection Glutathione
Leukocytes in Semen N-acetyl-cysteine
Smoking
Carnitine
Medication Coenzyme Q10
Drug abuse Lycopene
Picnogenol
Systemic diseases Pentoxifylline
Pollution Selenium
Shao-Fu-Zhu-Yu-Tang
Radiation Astaxanthin
Lepidium meyenii
-linolenic acid and lignans
Folic acid
22
Zinc
Esteves
23. Oral Antioxidants in Male
Our formula Infertility
Vitamin C 500mg
Vitamin E 400 mg
Folic acid 2 mg
Zinc 25 mg
Selenium 26 mcg
How long: minimum 2 months
From initiation of sperm production to ejaculation
Old concept ~80 days
New concept
Misell LM et al. J Urol. 2006
~60 days
23
Esteves & Agarwal. Novel concepts in male infertility. Int Braz J Urol 2011; 37 (1): 5-15
Esteves
24. Oral Antioxidant Therapy
for Male Infertility
1. Oxidative stress impairs sperm
function and is a risk factor for male
infertility and miscarriage (GR-A) .
2. Current evidence suggest that OA
supplementation for subfertile males
improve the chances for pregnancy
and live birth for couples undergoing
ART (GR-A).
3. Well-designed studies are needed to determine
the best candidates for AO therapy and which
formulation and dosages yield better results.
24
Esteves
29. Aromatase Inhibitors for
Infertile Obese Men
Serum Levels of Total
Testosterone and Estradiol
Normal > 10
T/E2 Ratio
𝟑𝟓𝟎 𝒏𝒈/𝒅𝑳
e.g.: 4.9 =
𝟔𝟐 𝒑𝒈/𝒎𝑳
T/E2 <10
Aromatase Hyperactivity
Anastrozole 1 mg
q1d 60-90 days
Zumoff et al. Reversal of the hypogonadotropic hypogonadism of obese men by administration of
29 the aromatase inhibitor testolactone. Metabolism 2003; 52: 1126. Raman & Schlegel Aromatase
inhibitors for male infertility. J Urol 2002; 167: 624.
Esteves
30. Aromatase Inhibitors for
Obesity-related Male Infertility
Anastrazole (1mg q1d for 3-6 months)
18
15.6 15.6
16
14 P <0.05
12
10
8
5.9 5.5
6
4 2.9 3.5
2
0
T/E ratio Ejaculate volume Sperm Count
(mL) (million/mL)
Pre-treatment Post-treatment
30 Raman JD, Schlegel PN. Aromatase inhibitors for male infertility. J Urol. 2002;167:624-9
Esteves
31. Aromatase Inhibitors for Obesity-
related Male Infertility
1. Obesity is a risk factor for male
infertility (GR-B).
2. Peripheral androgen aromatization is
enhanced in men with elevated BMI.
Obese men show increased plasma
estradiol and low testosterone levels
(GR-B).
3. Lowering estradiol levels, by administration of AI, increases
LH and FSH levels by pituitary modulation, and increase
testosterone levels (GR-A).
4. AI may stimulate sperm production (GR-C); effects upon
31
fertility are still to be determined.
Esteves