This document summarizes a presentation on the future of male infertility treatment. It discusses how sperm biomarkers, stem cells, and other emerging technologies may improve diagnosis and management. Specifically, it describes how sperm DNA and protein profiling could help identify healthy sperm for infertility treatment. It also reviews research showing stem cell-derived gametes in mice can generate offspring, suggesting a potential future option for men with no sperm production.
Sperm DNA Fragmentation (Oxidative stress, DNA damage and apoptosis, Test, Techniques, Relation to other semen parameters, Relationship to leucocytes, Relation to ICSI outcomes, Clinical applications, significance and limitations)
Iran march 2011
ABRASCT:
SPERM RETRIEVAL TECHNIQUES FOR THE AZOOSPERMIC MALE
Sandro C. Esteves, MD, PhD
Spermatozoa can be retrieved from either the epididymis or the testis, depending on the type of azoospermia, using different surgical methods such as PESA, MESA, TESA, TESE and micro-TESE.
In obstructive azoospermia (OA), sperm production is normal and gametes can be easily retrieved from the epididymis or the testicle in most cases, irrespective of the technique. PESA or TESA are simple and efficient methods for retrieving epididymal or testicular spermatozoa in men with OA. According to our data on OA, the etiology of the obstruction and the use of fresh or frozen-thawed epididymal/testicular sperm do not seem to affect ICSI outcomes in terms of fertilization, pregnancy, or miscarriage rates.
In cases of nonobstructive azoospermia (NOA), the efficiency of TESA for retrieving spermatozoa is lower than TESE, except in the favorable cases of men with previous successful TESA or testicular histopathology showing hypospermatogenesis. The use of microsurgery during TESE may improve the efficacy of sperm extraction with significantly less tissue removed, which ultimately facilitates sperm processing. Testicular histology results, if available, may be useful to predict the chances to retrieve sperm in men with NOA. Our data demonstrate that micro-TESE performs better than conventional TESE or TESA in cases of maturation arrest and Sertoli cell-only histological patterns, where tubules containing active focus of spermatogenesis can be positively identified using microsurgery. Testicular spermatozoa can be obtained even in the worst case scenario except in the cases of Y chromosome infertility with complete AZFa and/or AZFbmicrodeletions.
In both OA and NOA, sperm retrieval technique itself seems to have no impact on ICSI success rates. The main goal of PESA/TESA/TESE sperm processing is the recovery of a clean sample containing motile sperm. Such specimens are more fragile, and often compromised in motility, as compared to the ones obtained from ejaculates. Laboratory techniques should be carried out with great caution not to jeopardize the sperm fertilizing potential. Surgically-retrieved spermatozoa can be intentionally cryopreserved for future use. Spare left-over specimens that would be discharged after ICSI can also be cryostored. Different strategies can be developed according to each group’s results. If freezing of surgically-retrieved specimens provides results similar to those with the use of fresh sperm, then the use of freezing specimens would be preferable. If not, fresh specimens are preferable.
The reproductive potential of infertile men undergoing ART is related to the type of azoospermia. According to our data, the chances of retrieving spermatozoa (odds ratio [OR] = 43.0; 95% confidence interval [CI]: 10.3-179.5) and of achieving a live birth by ICSI (OR=1.86; 95% CI:l 1.03-2.89) were significantly increased in couples whose male partner had obstructive rather than non-obstructive azoospermia. Children conceived using sperm retrieved from men with OA and NOA should be followed-up because it is still unclear if there is an increased risk of birth defects when ICSI is carried out with non-ejaculated sperm.
References
Esteves SC, Glina S. Recovery of spermatogenesis after microsurgical subinguinal varicocele repair in azoospermic men based on testicular histology. IntBraz J Urol. 2005; 31:541-8.
Verza S Jr, Esteves SC. Sperm defect severity rather than sperm source is associated with lower fertilization rates after intracytoplasmic sperm injection. IntBraz J Urol. 2008,34:49-56.
Esteves SC, Verza S, Prudencio C, Seol B. Sperm retrieval rates (SRR) in nonobstructive azoospermia (NOA) are related to testicular histopathology results but not to the etiology of azoospermia. FertilSteril. 2010; 94(Suppl.):S132.
Esteves SC, Verza S, Prudencio C, Seol B. Success of percutaneous sperm retrieval and i
lecture delivered by Dr Sujoy Dasgupta in a Webinar organized by the Infertility Committee of FOGSI (Federation of Obstetric and Gynaecological Societies of India) and BOGS (Bengal Obstetric and Gynaecological Societiy), held in February, 2021
Sperm DNA Fragmentation (Oxidative stress, DNA damage and apoptosis, Test, Techniques, Relation to other semen parameters, Relationship to leucocytes, Relation to ICSI outcomes, Clinical applications, significance and limitations)
Iran march 2011
ABRASCT:
SPERM RETRIEVAL TECHNIQUES FOR THE AZOOSPERMIC MALE
Sandro C. Esteves, MD, PhD
Spermatozoa can be retrieved from either the epididymis or the testis, depending on the type of azoospermia, using different surgical methods such as PESA, MESA, TESA, TESE and micro-TESE.
In obstructive azoospermia (OA), sperm production is normal and gametes can be easily retrieved from the epididymis or the testicle in most cases, irrespective of the technique. PESA or TESA are simple and efficient methods for retrieving epididymal or testicular spermatozoa in men with OA. According to our data on OA, the etiology of the obstruction and the use of fresh or frozen-thawed epididymal/testicular sperm do not seem to affect ICSI outcomes in terms of fertilization, pregnancy, or miscarriage rates.
In cases of nonobstructive azoospermia (NOA), the efficiency of TESA for retrieving spermatozoa is lower than TESE, except in the favorable cases of men with previous successful TESA or testicular histopathology showing hypospermatogenesis. The use of microsurgery during TESE may improve the efficacy of sperm extraction with significantly less tissue removed, which ultimately facilitates sperm processing. Testicular histology results, if available, may be useful to predict the chances to retrieve sperm in men with NOA. Our data demonstrate that micro-TESE performs better than conventional TESE or TESA in cases of maturation arrest and Sertoli cell-only histological patterns, where tubules containing active focus of spermatogenesis can be positively identified using microsurgery. Testicular spermatozoa can be obtained even in the worst case scenario except in the cases of Y chromosome infertility with complete AZFa and/or AZFbmicrodeletions.
In both OA and NOA, sperm retrieval technique itself seems to have no impact on ICSI success rates. The main goal of PESA/TESA/TESE sperm processing is the recovery of a clean sample containing motile sperm. Such specimens are more fragile, and often compromised in motility, as compared to the ones obtained from ejaculates. Laboratory techniques should be carried out with great caution not to jeopardize the sperm fertilizing potential. Surgically-retrieved spermatozoa can be intentionally cryopreserved for future use. Spare left-over specimens that would be discharged after ICSI can also be cryostored. Different strategies can be developed according to each group’s results. If freezing of surgically-retrieved specimens provides results similar to those with the use of fresh sperm, then the use of freezing specimens would be preferable. If not, fresh specimens are preferable.
The reproductive potential of infertile men undergoing ART is related to the type of azoospermia. According to our data, the chances of retrieving spermatozoa (odds ratio [OR] = 43.0; 95% confidence interval [CI]: 10.3-179.5) and of achieving a live birth by ICSI (OR=1.86; 95% CI:l 1.03-2.89) were significantly increased in couples whose male partner had obstructive rather than non-obstructive azoospermia. Children conceived using sperm retrieved from men with OA and NOA should be followed-up because it is still unclear if there is an increased risk of birth defects when ICSI is carried out with non-ejaculated sperm.
References
Esteves SC, Glina S. Recovery of spermatogenesis after microsurgical subinguinal varicocele repair in azoospermic men based on testicular histology. IntBraz J Urol. 2005; 31:541-8.
Verza S Jr, Esteves SC. Sperm defect severity rather than sperm source is associated with lower fertilization rates after intracytoplasmic sperm injection. IntBraz J Urol. 2008,34:49-56.
Esteves SC, Verza S, Prudencio C, Seol B. Sperm retrieval rates (SRR) in nonobstructive azoospermia (NOA) are related to testicular histopathology results but not to the etiology of azoospermia. FertilSteril. 2010; 94(Suppl.):S132.
Esteves SC, Verza S, Prudencio C, Seol B. Success of percutaneous sperm retrieval and i
lecture delivered by Dr Sujoy Dasgupta in a Webinar organized by the Infertility Committee of FOGSI (Federation of Obstetric and Gynaecological Societies of India) and BOGS (Bengal Obstetric and Gynaecological Societiy), held in February, 2021
Every day, there is something new that may or may not have an impact on our daily practice. In this talk , we want to highlight some of these new developments
Clinical management of men with nonobstructive azoospermia - Steps Before Spe...Sandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Lecture 3: Steps Before Sperm Retrieval in Nonobstructive Azoospermia
American Urological Association (AUA) Lecture given at the American Society of Andrology (ASA) 40th annual conference, April 18 – 21, 2015 in Salt Lake City, Utah.
Clinical management of men with nonobstructive azoospermia - Role of IVF Labo...Sandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Lecture 5: Role of IVF Laboratory in Nonobstructive Azoospermia
Clinical management of men with nonobstructive azoospermia - Sperm Retrieval ...Sandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Lecture 4: Sperm Retrieval Methods in Nonobstructive Azoospermia
Clinical management of men with nonobstructive azoospermia - Azoospermia Diff...Sandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Lecture 1: Azoospermia Differential Diagnosis
Clinical management of men with nonobstructive azoospermia - Chances of Harve...Sandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Lecture 2: Chances of Harvesting Sperm in Nonobstructive Azoospermia
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.
Similar to Management of Male Infertility - What the future holds (20)
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?
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
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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
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!
Management of Male Infertility - What the future holds
1. Reproductive Andrology Surgery Workshop II
Reproductive Medicine Unit - Jahra Hospital - Kuwait 2014
Management of Male
Infertility
What the future holds
Sandro Esteves, MD., PhD.
Medical & Scientific Director, ANDROFERT
Campinas, Brazil
2. Learning objectives
At the completion of this presentation,
participants will have an overview of:
• Sperm biomarkers as diagnostic and treatment
tools
• Prospects of male fertility preservation
• Stem cells as new agents for the treatment of
male infertility
ANDROFERT
androfert.com.br
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 2
2014 December
3.
4. Irvin S, et al 1996, Auger J et al, 1995, Irvine DS 1994, Jørgensen N et al 2001,
Jørgensen N et al 2002, Swan SH 2003, Feki NC et al, 2009
ANDROFERT
androfert.com.br
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 5
2014 December
5. Male reproductive relatively simple
anatomy hides an overwhelmingly
complex system
ANDROFERT
androfert.com.br
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 6
2014 December
6. Spermatogenesis Process
ANDROFERT
androfert.com.br
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 7
2014 December
7. Genetic and
epigenetic-regulated
process
~2,000 genes, but only
30 in the Y
chromosome
Hamada et al 2012
ANDROFERT
androfert.com.br
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 8
2014 December
8. Extremely specialized cell type
ANDROFERT
androfert.com.br
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 9
2014 December
9. Unexplained infertility affects up
to 40% of infertile men
1 in 100 men have no
sperm in ejaculate
(azoospermia)
Up to 50%
aspermatogenic
(absolute sterility)
ANDROFERT
androfert.com.br
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 10
2014 December
10. Limitations of current management
Conventional
semen analysis
Conventional
surgeries
Empirical
medical
treatments
ART overuse
ANDROFERT
androfert.com.br
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 11
2014 December
11. Recent Advancements
Sperm Function
Testing
Microsurgery
Genetic
diagnosis
ANDROFERT
androfert.com.br
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 12
2014 December
YCMD
molec
ular
diagno
sis by
PCR
12.
13. The Era of Biomarkers
Genomics
Transcriptomics
Proteomics
Metabolomics
ANDROFERT
androfert.com.br
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 14
2014 December
14. Researchers first to determine entire
genetic sequence of individual sperm
We can look at a
particular individual,
make some calls about
what they would likely
contribute genetically to
an embryo and perhaps
even diagnose or detect
potential problems, and
identify healthy sperm
for use in IVF
ANDROFERT
androfert.com.br
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 15
2014 December
15. DNA Micro-array Technology
Normalcy of Sperm
Chromatin Content
• Glass or silicon slides
where thousands of
features are arrayed
• Gene expression is
measured hybridization
process
• Microarrays are read using
laser-based fluorescence
scanners
• Determine which genes are
active and at what levels
• Compare with controls, etc.
ANDROFERT
androfert.com.br
ANDROFERT
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2014 December
16. ANDROFERT
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2014 December
17. Potential Clinical Applications of
Sperm Molecular Genetic
Fingerprinting
• Infertility diagnosis
• Assessment of
treatment outcome
(medical, surgical)
• ART outcome (IUI,
IVF, ICSI)
• Sperm selection
techniques
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2014 December
18. ANDROFERT
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Seminal Fluid Molecular Genetic
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Fingerprinting
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2014 December
19. ANDROFERT
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S ESTEVES, 20
2014 December
20. Proteins are also critical to
understanding disease
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2014 December
21. Proteomics
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2014 December
Mass Spectroscopy
Raman Spectroscopy
Nuclear Magnetic
Resonance
22. ANDROFERT
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ANDROFERT
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2014 December
23. Sperm & Seminal Plasma Proteomic
Profiles
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S ESTEVES, 24
2014 December
25. Change in proteomic profiling in seminal
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plasma of adult men before and after
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varicocelectomy
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2014 December
Camargo M et al. Hum. Reprod. 2013;28:33-46
26.
27. Sperm,
spermatids
Embryos
Oocytes
Ovarian tissue
?Male germ cells
?Testicular
tissue
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S ESTEVES, 28
2014 December
28. ANDROFERT
androfert.com.br
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 29
2014 December
29. ANDROFERT
androfert.com.br
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 30
2014 December
30. ANDROFERT
androfert.com.br
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2014 December
31. Spermatogonial stem cell
preservation and transplantation
• Boys facing gonadotropic treatment
• Klinefelter syndrome patients
Cryopreservation before SSC loss
• Extraction: testicular biopsy
• Freezing : slow-freezing and storage of testicular
tissue or cell suspension in LN
• Cryoprotectant: DMSO
• Grafting: ectopic or homotopic (mouse)
• When to graft: unknown
• Fertilizing capacity in humans: unknown
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32.
33. Nonobstructive azoospermia
irreversible condition
Congenital
Testicular dysgenesis/cryptorchidism
Genetic abnormalities (Klinefelter syndrome, Yq microdeletions, etc.)
Acquired
Testicular torsion; Trauma
Post-inflammatory (eg. Mumps orchitis)
Exogenous factors (eg. Cytotoxic drugs, irradiation)
Testicular cancer
Systemic diseases (eg. Liver cirrhosis, renal failure)
Idiopathic (Unknown etiology)
Esteves et al. Clinics 2011; 66: 691-700
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2014 December
34. Current method for identification of sperm
production sites in nonobstructive
azoospermia
Esteves et al Int Braz J Urol 2013; 37: 570-83; Deruyver et al Andrology 2014; 2: 20-4
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2014 December
35. Morphometric Evaluation of
Seminiferous Tubules
Median
25%-75%
5%-95%
Raw Data
yes No
Presence of Sperm
420
400
380
360
340
320
300
280
260
240
220
200
180
160
Max. Tubule Diameter
Verza Jr S, Esteves SC. Fertil Steril 2012; 98: S242
N=54; Tubule Diameter: KW-H (1;54) = 25.2; P<0.001
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S ESTEVES, 36
2014 December
36. Novel methods for identification of sperm
production sites in men with nonobstructive
azoospermia
Multi-photon microscopy
(ex vivo; human model)
Confocal fluorescence
microscopy
(in vivo; murine model)
Full-field optical coherence
tomography
(ex vivo; rat model)
Najari et al, J Urol 2012; Smith et al J Urol 2012; Ramasamy et al., J Pathol Inform 2012
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2014 December
37. No residual sperm production in
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up to 50% of men with NOA
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2014 December
38. In mice, transplanted stem cell-derived
male gametes resulted in
proper spermatogenesis
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2014 December
39. In mice, derived gametes generate
viable offspring
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2014 December
Aponte et al, Clinics 2013
40. Biotechnological advancements in the
treatment of aspermatogenic men
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41. Conclusions
proteomic biomarkers could
add to work-up and clinical
treatment strategies
• Advances in immature germ cells
cryopreservation/transplantation will expand
fertility options for oncological boys
• Biotechnological approaches for generating
male gametes last frontier to be accomplished
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• Novel genomic and
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42. Why we should do all that …
Courtesy of E.N. & T.A.S. with permission
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Editor's Notes
50-80 million people worldwide
It has been estimated that 2,000 genes are essential for spermatogenesis, from which only 30 genes are present in Y chromosome and most of the remaining genes are on the autosomal chromosomes.
The researchers also identified 25 to 36 new single nucleotide mutations in each sperm cell that were not present in the subject's diploid genome. Such random mutations are another way to generate genetic variation, but if they occur at particular points in the genome they can have deleterious effects.
Various conditions that include genetic and congenital abnormalities, post-infectious, exposure to gonadotoxins, medications, varicocele, trauma, endocrine disorders, and idiopathic may cause NOA
Stem cell-derived male gametes. Several growth factors and cytokines are used for in vitro differentiation of pluripotent cells into male gametes/SSC-like cells. The transplantation of stem cell-derived SSC-like cells in sterile mice results in proper spermatogenesis.
Pluripotent stem cells open new perspectives in the treatment of patients with azoospermia. Although the use of ESCs is connected with many ethical concerns, there are no ethical issues regarding the use of iPSCs. Moreover, ESCs are genetically unrelated to the patients, while it may be possible to get offspring with their own genetics by using iPSCs in derivation of functional male gametes.