This document summarizes Sandro Esteves' presentation on optimizing ART success through individualizing oocyte retrieval targets based on a patient's age and ovarian reserve. It discusses:
1) The decline in blastocyst euploidy rates with increasing female age and the importance of oocyte quantity and quality for ART success.
2) The Poseidon criteria for stratifying "low prognosis" ART patients based on age and expected oocyte yield.
3) A mathematical model developed to estimate the minimum number of oocytes needed to achieve at least one euploid blastocyst based on a patient's age.
4) How individualizing treatment based on this oocyte target number can maximize ART efficiency
Since the first formal description of LPD in 1949 as a possible cause of infertility and recurrent miscarriage by Jones. Innumerable investigations have been undertaken in an effort to verify its existence or to characterize its pathophysiology, diagnosis, and treatment. The consensus of the literature is that LPD does exist and that its cause is multifactorial like abnormal folliculogenesis, inadequate LH surge,inadequate secretion of progesterone by the corpus luteum, aberrant end-organ response by the endometrium.
Since the first formal description of LPD in 1949 as a possible cause of infertility and recurrent miscarriage by Jones. Innumerable investigations have been undertaken in an effort to verify its existence or to characterize its pathophysiology, diagnosis, and treatment. The consensus of the literature is that LPD does exist and that its cause is multifactorial like abnormal folliculogenesis, inadequate LH surge,inadequate secretion of progesterone by the corpus luteum, aberrant end-organ response by the endometrium.
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
Role of adjuvants in poor ovarian responders , undergoing infertility treatment , in terms of Intra uterine inseminations ( IUI ) to In Vitro Fertilization ( IVF )
IUI is a basic but effective form of fertiltiy treatment and can be a viable alternative to the expensive IVF / test tube baby treatment that is normally advised.
This presentation will be very useful for the practising gynecologists, IVF specialists and General practitioners who perform IUI.
Even patients on going through this presentation will be more educated about iui.
Please reach out to me on 9833032120 by whatsapp / Telegram or phone call or email on dalalsj@gmail.com for further details / treatment options.
Significant increase in live birth rate is found when IUI is done with stimulation compared with IUI in natural cycle in women with Unexplained Infertility .
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
Role of adjuvants in poor ovarian responders , undergoing infertility treatment , in terms of Intra uterine inseminations ( IUI ) to In Vitro Fertilization ( IVF )
IUI is a basic but effective form of fertiltiy treatment and can be a viable alternative to the expensive IVF / test tube baby treatment that is normally advised.
This presentation will be very useful for the practising gynecologists, IVF specialists and General practitioners who perform IUI.
Even patients on going through this presentation will be more educated about iui.
Please reach out to me on 9833032120 by whatsapp / Telegram or phone call or email on dalalsj@gmail.com for further details / treatment options.
Significant increase in live birth rate is found when IUI is done with stimulation compared with IUI in natural cycle in women with Unexplained Infertility .
Background: Cervical screening through conventional cervical cytology is most commonly used throughout the world. The Cervical cancer is the second most common cancer worldwide and in developing countries, the leading cause of death. It is one of the most preventable and curable of all cancers.
Objective: To Study the role of Pap smear in detecting neoplastic and non-neoplastic lesions of cervix and to determine the occurrence of various lesions in remote area of Bagalkot.
Methods: This is prospective study of 240 women with age group 20 to 60 years was carried out from May 2015 to June 2016 cytology section of pathology department, S. Nijalingappa Medical College & H.S.K Hospital & Research Centre, Bagalkot, India. Pap smears were prepared, fixed, stained and carefully examined.
Results: In this study, Reactive cellular changes associated with inflammation was the most common with 182 cases (75.8%) followed by Low-grade squamous intraepithelial lesions (SIL) with 11 cases (4.5%), then atypical squamous epithelial cells of undetermined significance 8 cases (3.3%), High-grade squamous intraepithelial lesions with 5 cases (2.1%), Atrophy with 3 cases (1.3%) and Atypical Glandular Cell in 3 cases (1.3%). The average age of women for all the epithelial abnormalities was 40 years.
Conclusion: This study will increase awareness of the Pap test and cervical cancer, thereby paving a way for the prevention of cervical cancer.
Key-words- Pap smear, Cervical cancer, The Bethesda System, Squamous intraepithelial lesions (SIL)
Fetal growth restriction (FGR), formerly called intrauterine growth restriction (IUGR), refers to a condition in which an unborn baby is smaller than it should be because it is not growing at a normal rate inside the womb.
Mild FGR usually doesn't cause long-term problems. In fact, most babies who have it catch up in height and weight by age 2. But severe FGR can seriously harm a baby before and after birth. The extent of the problems depends on the cause and how severe the growth restriction is. It also depends on what point in the pregnancy it starts.
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
Similar to Oocyte number, female and male age, and ART outcomes (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?
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
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 - 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
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
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
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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.
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.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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
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
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
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.
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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
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...
Oocyte number, female and male age, and ART outcomes
1. Sandro C. Esteves
ANDROFERT & University of Campinas (UNICAMP),
Campinas, BRAZIL
Aarhus University, DENMARK
Oocyte number and
success in ART –
The “ART Calculator”
2. Esteves, 2
Sandro Esteves, MD., PhD.
• Medical and Scientific Director, ANDROFERT, Campinas, BRAZIL
• Collaborating Professor, Department of Surgery, University of Campinas
(UNICAMP), BRAZIL
• Research Collaborator, American Center for Reproductive Medicine, Cleveland
Clinic, USA
• Research Collaborator, Genetic Unit, Universidad Autónoma de Madrid, SPAIN
• Honorary Professor of Reproductive Endocrinology, Faculty of Health, Aarhus
University, DENMARK
Declare receipt of honoraria for lectures from Merck, Besins, Gedeon
Richter, and Lilly
Affiliation & Disclosure
3. 1. Importance of oocyte number and female age in
ART success
2. Estimation of individualized oocyte number for
modelling patient-oriented strategies as a
means to increase ART efficiency
Lecture Outline
Esteves, 3
4. Modified from Smith et al. JAMA 2015
156,947 UK women
(257,398 IVF cycles;
cumulative LBR using
fresh and frozen ET)
With increased women’s age in ART programs,
we should maximize reproductive outcomes and shorten TTLB
Esteves, 4
5. Quality Dimensions
1. Effectiveness (Technical aspects to deliver the best outcome)
2. Safety (risks, adverse effects, lab quality, etc.)
3. Patient centeredness (patient values and preferences)
Success in ART
The bottom line
• Evaluate properly
• Give a fair estimate of outcome
• Develop a time-limited treatment plan
Dancet et al. Hum Reprod 2011; Mainz. Int J Qual Health Care 2003
Esteves, 5
6. AMH and AFC predict ovarian response but not LBR
AMH~AFC>FSH>Age
Predictors of Poor
Response
Predictors of Excessive
Response
Accuracy for Non-Pregnancy
Prediction ~ 50-55%
Modified from Broer et al. Fertil Steril 2009 Modified from Broer et al. Fertil Steril 2009Modified from Broer et al. Hum Reprod Update 2011
Accuracy ~0.82 Accuracy ~0.78
Esteves, 6
7. Female age and number of oocytes can predict LBR
Modified from McLernon et al. BMJ 2016
Modified from Sunkara et al. Hum Reprod 2011
Modified from De Geyter et al. Swiss Med Wkly 2015
Esteves, 7
9. Low prognosis groups
Young Older
Adequate
ovarian
reserve
Poor
ovarian
reserve
Courtesy of Chloe Xilinas, EXCEMED
Poseidon Group. Fertil Steril 2016; Humaidan et al. F1000Research 2016
2
2
Esteves, 9
10. Prevalence of low prognosis patients according
to POSEIDON criteria
5% 30%
10% 55%
47%
Poseidon
1-4
53%
Non Poseidon
N=432 – YEAR 2017
Source: ANDROFERT
Esteves, 10
11. Modified from Drakopoulos et al. Hum Reprod 2016
Low Prognosis Owing to Decreased Number of Oocytes
and thus lower CLBR
Poseidon Patients
Age-adjusted CLBR strongly influenced by oocyte number
* Age adjusted (OR: 0.9; 95% Cl: 0.9-1.01)
21.7%
39.7%
50.5%
61.5%p=0.002
p=0.02
p=0.01
Esteves, 11
12. Group 1
Young & Suboptimal/Low
Oocyte Number
Group 2
Old & Suboptimal/Low
Oocyte Number
Group 3
Young & Expected Low
Oocyte Number
Group 4
Old & Expected Low
Oocyte Number
High
embryo
aneuploidy
risk
Low
embryo
aneuploidy
risk
Few embryos generated
Reduced Cumulative Live Birth Rate
Poseidon
Patients
Esteves, 12
13. Esteves et al., ESHRE 2018; P-394
The older the women the lower the probability of euploid
embryos, thus increasing the risk of NO transferable embryos
Euploidy probability vs Female age
Cycles with no transferable embryos
Courtesy of Chloe Xilinas, EXCEMED
Courtesy of Ubaldi & Rienzi. Genera
Jan 2012 – Dec 2013
Esteves, 13
14. Estimation of Age-dependent Decrease in Blastocyst
Euploidy by Next Generation Sequencing - Development of
a Novel Prediction Model
Quadratic model on age significant (Prob>ChiSquare=0.028);
derived model was log[p(t)/(1−p(t))]=7.575-0.21⋅age-0.011⋅(age-38.41)2,
where p(t) is the probability of a blastocyst being euploid for age (t) in years.
Term Estimate Std Error Wald
ChiSquare
Prob >
ChiSquare
Lower
95%
Upper
95%
Intercept
7.5746663 1.028021 54.290324 <.0001* 5.5597808 9.5895518
age
-0.212288 0.026273 65.284544 <.0001* -0.263783 -0.160793
(age-
38.4082)*(age-
38.4082)
-0.01059 0.004834 4.7979866 0.0285* -0.020066 -0.001114
Esteves, Carvalho, Martinhago, Melo, Bento, Humaidan & Alviggi. Panminerva Medica 2018 ahead of print
Esteves, 14
15. Euploidy probability vs Female age
Measure
Training Validation
Number of rows
1,036 260
Sum of
Frequencies 1,036 260
-LogLikelihood
588.50165 139.70103
Number of
Parameters 3 3
BIC
1197.6537 295.89356
AICc
1183.028 285.50206
Generalized
RSquare 0.1162863 0.1893375
Validation by randomly splitting 80% of the data
for training and 20% for testing
Esteves, Carvalho, Martinhago, Melo, Bento, Humaidan & Alviggi. Panminerva Medica 2018 ahead of print
Esteves, 15
16. Esteves et al., ESHRE 2018; O-007
Progressive decline* in blastocyst euploidy
probability as a function of female age
Analysis of 1,220 trophectoderm biopsies from 436 patients undergoing
ICSI and PGT-A with NGS
1.2 1.9 2.6 3.4 4.4
5.5
6.7
8.2
9.8
11.6
13.6
15.7
17.9
20.2
22.4
24.5
26.6
Geometric mean of the yearly variation: 13.6%
*The % decrease in blastocyst euploidy
probability from year (t) to year (t+1) was
defined as the ratio p(t+1)/p(t) x 100
Esteves, 16
17. Number of oocytes needed to maximize live births should be
individualized
Female age is a critical factor to
be taken into account
Patient-oriented strategies can
be used to achieve the
individualized oocyte number
Esteves, 17
18. Introduced an Intermediate Marker of Success in ART:
the Ability to Retrieve the Number of Oocytes Needed to Obtain
at Least One Euploid Blastocyst for Transfer in Each Patient
Poseidon Group. Fertil Steril 2016; Humaidan et al. F1000Research 2016
What is new in POSEIDON?
Introduced the Concept of ‘Low Prognosis’ in ART
Combined Oocyte Quality and Quantity for Identification
and Stratification of the ’Low Prognosis’ Patient
Included ’Hypo-responders’ as a Distinct Category
of ’Low Prognosis’ Patients
Introduced an Intermediate Marker of Success in ART:
the Ability to Retrieve the Number of Oocytes Needed to Obtain
at Least One Euploid Blastocyst for Transfer in Each Patient
Esteves, 18
19. Courtesy of Ubaldi & Rienzi (GENERA; Jan 2012-Dez 2013)
Source: ANDROFERT; Jan 2015-Sept 2016 (PGT-A by NGS)
Live birth (%)
Availability of euploid embryos maximizes IVF efficiency by
offsetting the negative effect of age on implantation and
pregnancy
Esteves, 19
20. http://www.members.groupposeidon.com/Calculator
Estimation can be done by means of a mathematical function
taking into account relevant predictive factors
Input variables
• Maturation rate
• 2PN Fertilization rate
• Cleavage or Blastulation rate
• Euploidy rate per age group
Adjusted according to maternal
and paternal age, sperm source,
sperm and oocyte status,
and type of embryo transfer
(fresh; FET)
Output variable
Y (N oocytes)
Function
Y = f(X)
Esteves, 20
21. There are two ways to do that…
the HARD WAY the EASY WAYand
Esteves, 21
26. The most optimal treatment strategy is planned with the
mindset to achieve the POSEIDON marker of success
GnRH analogue regimen
Gonadotropin dose and drug type
Trigger strategy
Adjuvant therapy
Combined strategies (AccuVit; Duostim, etc.)
Personalized use of laboratory technology
Personalized luteal phase support
Esteves, 26
27. Agonist or Antagonist +
rFSH alone or rFSH + LH
Agonist or Antagonist + rFSH + LH
GnRH Antagonist + Low dose rFSH (100-175 IU) GnRH Antagonist + rFSH + LH
Poseidon
G1 Poseidon
G2 Poseidon
G3 Poseidon
G4
Non
Poseidon
patients
Andersen et al. (eds.) Research Topic Frontiers in Endocrinology. In preparation
It is important to use the right FSH starting dose and adapt it during
the cycles to optimize the number of oocytes retrieved and at the
same time minimize risks such as OHSS and cycle cancellation
Esteves, 27
28. Esteves, Yarali, Ubaildi et al. Validation of ART Calculator Consortium;
Unpublished data
No detrimental effects on embryo ploidy in patients
who retrieve more oocytes
Response Number Euploid Blastocysts
Distribution Binomial
Estimation Method Logistic Regression
Validation Method Validation Column
Probability Model Link Logit
Generalized Regression for number
Euploid Blastocysts Model Launch
Lasso [x] Adaptive
Term Estimate Std Error
Wald
ChiSquare
Prob >
ChiSquare
Lower
95%
Upper
95%
Intercept 6.2769104 0.6256681 100.64771 <0.0001* 5.0506235 7.5031972
Age Female -0.182507 0.152275 143.64894 <0.0001* -0.212352 -0.152662
Number
Blastocysts
0.0302516 0.0189943 2.536584 0.1112 -0.006977 0.0674797
Parameter Estimates for Original Predictors
3,108 Trophectoderm Biopsies
1,109 patients
Euploidy probability vs. number
of blastocysts by age group
Esteves, 28
29. Higher ovarian response than that achieved with mild/natural
ovarian stimulation does not increase risk of embryo aneuploidy
Term Estimate Std Error
Wald
ChiSquare
Prob >
ChiSquare
Lower
95%
Upper
95%
Intercept 3.8117137 1.5331832 6.1809102 0.0129* 0.8067298 6.8166876
Age Female -0.22129 0.019748 125.56789 <0.001* -0.259996 -0.182585
typeOSGrou
ped[Convent
ional-Other]
0.065727 0.33909 0.0375714 0.8463 -0.598877 0.7303311
Response Number Euploid Blastocysts
Distribution Binomial
Estimation Method Adaptive Lasso
Validation Method Validation Column
Probability Model Link Logit
Adaptive Lasso with Validation Column Model Summary
Parameter Estimates for Original Predictors
1,632 Trophectoderm Biopsies by NGS
631 patients
Euploidy probability vs Female Age, by OS Type
Esteves, Yarali, Ubaildi, et al. Validation of ART Calculator Consortium;
Unpublished data
Esteves, 29
30. Administration of an inappropriately low gonadotrophin dose
may lead to the growth of a low number of follicles resulting
in an ‘iatrogenic’ poor or suboptimal response
• Type of Gonadotropin
• FSH Dose
• Add LH
Courtesy of Chloe Xilinas, EXCEMED
Esteves, 30
31. Unpublished data; Source: ANDROFERT
Current Practice – Flexibility of iCOS
Rec-hFSH
Starting Dose Distribution (%)
% cycles with
Dose Adaptation after Sd5
53.4%
Esteves, 31
32. Current Practice – Flexibility of iCOS
% cycles
by Trigger Method
% cycles
with LH Activity Supplementation
12%
Dual trigger
43%
GnRH analog
45%
hCG
57%
Rec-LHc
43%
No-LH
Unpublished data; Source: ANDROFERT
Esteves, 32
33. Target number of oocytes difficult to achieve by a single OS cycle
http://www.members.groupposeidon.com/Calculator
Courtesy of Chloe Xilimas, EXCEMED
Esteves, 33
34. Haahr, Esteves & Humaidan. Reprod Biol Endocrinol 2018
Management of Poseidon poor prognosis patients
<AFC <5 and/or AMH <1.2 ng/ml
Group 3, young (AGE <35) Group 4, old (AGE ³35)
Poor reserve - good quality Poor reserve - poor quality
Reason for poor response:
• Poor ovarian reserve
• Asynchronous development
(Genetic polymorphism of FSH-R; LH-R; V-LH-β)
iCOS Treatment:
• Long GnRHa protocol
• GnRH antagonist (E2, OCP)
• DuoStim ?
• Stimulation with 300 IU/d rFSH
• Androgens ?
Embryo Transfer strategy:
• Fresh transfer
• Oocyte/embryo accumulation and FET
Measure of success:
In average, a total of 4-5 oocytes are needed
to obtain one euploid embryo
Reason for poor response:
• Poor ovarian reserve
• Asynchronous development
• High Aneuploidy rate
(Genetic polymorphism of FSH-R; LH-R; V-LH-β)
iCOS Treatment:
• Long GnRHa protocol
• GnRH antagonist (E2, OCP)
• DuoStim
• Stimulation with 300 IU/d rFSH
• Androgens ?
Embryo Transfer strategy:
• Fresh transfer
• Oocyte/embryo accumulation, PGS?
and FET (Oocyte donation)
Measure of success:
In average, a total of 12 oocytes are needed
to obtain one euploid embryo
Esteves, 34
35. Modified from Ubaldi et al. Fertil Steril 2016
Dual stimulation
Courtesy of Chloe Xilinas, EXCEMED
rFSH or rFSH+LH rFSH or rFSH+LH
Esteves, 35
39. Review Criteria
An extensive search of studies examining the influence of paternal age on
ART outcomes was performed using PubMed and MEDLINE. The start date
for the search was January 2008, and the end date was March 2018.
The overall strategy for study identification and data extraction was based on
the following keywords: “paternal age”, “male age factor”, “masculine age
factor”, “male ageing”, “paternal ageing”, “reproductive techniques”,
“assisted”, “ICSI”, “in vitro fertilization” “sperm injections”, “intracytoplasmic”,
“IVF”, with the filters “humans” and “English language.” Data that were solely
published in conference or meeting proceedings, websites or books were not
included. Citations dated outside the search dates were only included if
provided conceptual content.
ESTEVES, 39CLÍNICA DE ANDROLOGIA E LABORATÓRIO DE REPRODUÇÃO HUMANA
CENTRO DE REFERÊNCIA PARA REPRODUÇÃO MASCULINA ESTEVES, 39
40. Study Country Number Main findings Age cutoff
Frattarelli
2008
USA 1023
Decline in semen volume and total motile sperm
number
45
Bellver 2008 Spain 2698
Negative association between age and semen volume,
sperm concentration, and total progressive motility
NR
Girsh, 2008 Israel 484 Male age higher in non-pregnant group; Conventional
semen parameters lower in men aged >50
50
Ferreira, 2010 Brazil 1024 No effect of age on sperm concentration and motility NR
Duran 2010 USA 408
Semen volume, sperm motility and fertilization rates
inversely correlated with age
NR
Nijs, 2011 Belgium 278
No correlation between male age and sperm
concentration, progressive motility, and DFI
NR
Varshini, 2011 India 504 DFI increased in men older than 40 years 40
Stone, 2013 USA 5081
Total sperm numbers fall by ~2% per year, morphology
by ~0.8% per year, and total sperm motility by ~2%
35
Alshahrani,
2014
USA 472
No significant differences in conventional semen
parameters. Higher DFI in men >40y
40
Beguería, 2014 Spain 4887
Semen volume and %motile sperm decreased with a
mean reduction of 0.22 ml and 1.2% every 5 years
NR
Kaarouch,
2018
Morocco 204
No effect on conventional semen parameters; Higher
DFI and sperm aneuploidy in older men
40
Paternal age X semen parameters
Bertoncelli Tanaka et al. Panminerva Med. 2018 Jul 18. [Epub ahead of print]
41. Author Country
Number
(cycles)
Method
Egg donation
model
Fertilization Embryo
development
Pregnancy
Miscarriage/
stillbirth
Live birth Age cutoff
Gu, 2012 China 103 IVF Yes No effect NR No effect No effect No effect NA
Robertshaw, 2014 USA 237 IVF Yes NR NR NR
Increase in pregnancy loss
with aging
26% lower odds of LB with each 5-
year increase in age
NR
Wu, 2015 China 9991 IVF No No effect No effect
Lower in men >36y than
<32 y (women 30-34y)
No effect No effect 36
Girsh, 2008 Israel 484 ICSI Yes No effect Decreased Decreased NR NR 40-50
Ferreira, 2010 Brazil 1024 ICSI No NR No effect
Decreased by 5% for
each year of age in
oligozoospermia
No effect NR NR
Tsai, 2013 Taiwan 184 ICSI No No effect No effect No effect No effect No effect NA
Ramasamy, 2014 USA 1046 ICSI No NR NR Decreased NR NR 50
Beguería, 2014 Spain 4887 ICSI Yes No effect No effect No effect No effect No effect NA
Frattarelli, 2008 USA 1023 IVF and ICSI No No effect
Reduced blastocyst
formation
No effect Increased miscarriage Decreased 55
Bellver, 2008 Spain 2698 IVF and ICSI Yes No effect No effect No effect No effect NR NA
Campos, 2008 Spain 915 IVF and ICSI Yes No effect No effect Decreased No effect NR 39
Luna, 2009 USA 672 IVF and ICSI Yes Decreased
Reduced blastocyst
formation
No effect No effect NR 40* and 60‡
Duran, 2010 USA 519 IVF and ICSI Yes Decreased No effect No effect No effect No effect 50
Ghuman, 2016 UK 7104 IVF and ICSI No NR NR No effect No effect NR NA
Meijerink, 2016 Netherlands 7051 IVF and ICSI No No effect No effect No effect NR NR NA
McPherson, 2017 Australia 2215 IVF and ICSI No No effect NR See LBR NR
10% lower pregnancy and LBR in
women aged 35 years with
partners >40 years than women
aged 35 years with partners <30
years
40
Tiegs, 2017 USA 573 IVF and ICSI Yes Decreased No effect No effect No effect No effect 45
Chapuis, 2017 France 2491 IVF and ICSI No No effect
Reduced blastocyst
formation
Decreased in ICSI but
not with IVF
No effect — 50
Park, 2017 Korea 452 ICSI No No effect No effect Decreased NR Decreased 46
Kaarouch, 2018 Morocco 83 IVF No Decreased Decreased Decreased Increased NR 40
Bertoncelli Tanaka et al. Panminerva Med. 2018 Jul 18. [Epub ahead of print]
Paternal age X IVF outcomes
ESTEVES, 41
42. ESTEVES, 42
ESTEVES, 42
CLÍNICA DE ANDROLOGIA E LABORATÓRIO DE REPRODUÇÃO HUMANA
CENTRO DE REFERÊNCIA PARA REPRODUÇÃO MASCULINA
43. ESTEVES, 43
Esteves, Yarali, Ubaldi et al; ART Calculator Validation Consortium, Unpublished
data
Paternal age and
blastocyst genetic status
1070
patients
TB + NGS
CLÍNICA DE ANDROLOGIA E LABORATÓRIO DE REPRODUÇÃO HUMANA
CENTRO DE REFERÊNCIA PARA REPRODUÇÃO MASCULINA ESTEVES, 43
44. Age
CLÍNICA DE ANDROLOGIA E LABORATÓRIO DE REPRODUÇÃO HUMANA
CENTRO DE REFERÊNCIA PARA REPRODUÇÃO MASCULINA ESTEVES, 44
Cho, Esteves, Agarwal. Curr Opin Obstet Gynecol 2016
Finding the link
45. Aitken, Reproduction 2014; 147:S1-S11
Mechanism of oxidative-induced sperm DNA damage
OGG1: 8-oxi guanine glicosylase
CLÍNICA DE ANDROLOGIA E LABORATÓRIO DE REPRODUÇÃO HUMANA
CENTRO DE REFERÊNCIA PARA REPRODUÇÃO MASCULINA ESTEVES, 45
Activity of OGG1 decreases with advanced paternal
age, thus resulting in 8-oxi guanine accumulation
46. Sperm chromatin repair mechanisms
CLÍNICA DE ANDROLOGIA E LABORATÓRIO DE REPRODUÇÃO HUMANA
CENTRO DE REFERÊNCIA PARA REPRODUÇÃO MASCULINA ESTEVES, 46
Champroux et al. Basic and Clin Androl 2016; 26:17
OGG1 is deficient
in oocytes;
8OHdG carried to
embryos by
fertilizing sperm
8OHdG highly
mutagenic (G-T
transversion)
47. proband schizophrenic Kong et al. Nature 2012; 488:471
proband a parent of an autistic case
♦ proband autistic
An exponential model estimates
paternal mutations doubling every
16.5 years
Paternal age and germline mutations
CLÍNICA DE ANDROLOGIA E LABORATÓRIO DE REPRODUÇÃO HUMANA
CENTRO DE REFERÊNCIA PARA REPRODUÇÃO MASCULINA ESTEVES, 47
48. Guanine
particularly
vulnerable
Oxidative stress causes harm to DNA
No.oxidizedregions
Chromosome size
Imunoprecipitação 8OHdG
chrX
chrY
chr15
CLÍNICA DE ANDROLOGIA E LABORATÓRIO DE REPRODUÇÃO HUMANA
CENTRO DE REFERÊNCIA PARA REPRODUÇÃO MASCULINA ESTEVES, 48
49. Impact of paternal age on
neurodevelopmental status of naturally
conceived offspring
Autism
Bipolar disease/schizophrenia
Marfan syndrome
Paternal age (yrs)
Oddsratio
Bipolar disease
Frans et al. Arch Gen
Psychiatry 2008;
65:1034
Paternal age (yrs)
Oddsratio
Autism
Reichenberg et al. Arch
Gen Psychiatry 2006;
63:1026
CLÍNICA DE ANDROLOGIA E LABORATÓRIO DE REPRODUÇÃO HUMANA
CENTRO DE REFERÊNCIA PARA REPRODUÇÃO MASCULINA ESTEVES, 49
50. POSEIDON–based
Stratification
FSH Starting Dose
Gonadotropin Dose
Adaptation
Flexible OS
(eg. LH, Duostim,
trigger)
Maximize oocyte yield
to achieve estimated
N oocytes for at least
1 euploid embryo
(ART Calculator)
Reduced
Time to Live Birth
Conclusions
Esteves, 50