Role of progestogens in obstetrics and gynecologyAhmad Saber
The
different progestogens with their overlapping effects on estrogen, androgen, glucocorticoid,
and mineralocorticoid receptors are described in order to allow the clinician to make the most appropriate choice of progestogen.
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 .
Ovulation Stimulation Protocols for IUI - Dr Dhorepatil BharatiBharati Dhorepatil
What are important factors to be considered important
Ovarian reserve
Previous ovarian response
Basic hormone profile
Role of LH
Trigger
Luteal phase support
Pregnancy rate/cycle
Role of progestogens in obstetrics and gynecologyAhmad Saber
The
different progestogens with their overlapping effects on estrogen, androgen, glucocorticoid,
and mineralocorticoid receptors are described in order to allow the clinician to make the most appropriate choice of progestogen.
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 .
Ovulation Stimulation Protocols for IUI - Dr Dhorepatil BharatiBharati Dhorepatil
What are important factors to be considered important
Ovarian reserve
Previous ovarian response
Basic hormone profile
Role of LH
Trigger
Luteal phase support
Pregnancy rate/cycle
treating anemia is a big challenge.oral iron therapy do not adequately treat IDA. IV ferric carboxy maltose (FCM)effectively treats IDA by circumventing the problem compliance of oral iron therapy.
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
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Insulin is synthesized in the β cells of pancreatic islets as a single chain peptide Preproinsulin (110 AA) from which
treating anemia is a big challenge.oral iron therapy do not adequately treat IDA. IV ferric carboxy maltose (FCM)effectively treats IDA by circumventing the problem compliance of oral iron therapy.
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
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Insulin is synthesized in the β cells of pancreatic islets as a single chain peptide Preproinsulin (110 AA) from which
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.
These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Insulin is synthesized in the β cells of pancreatic islets as a single chain peptide Preproinsulin (110 AA) from whic
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.
These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Excess of hyperglycemic hormones (glucagon, ete. ) obesity: ; cause relative insulin deficiency the β cells Tag behind
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
“... good health is more than just exercise and diet. It’s really a point of view
and a mental attitude you have about yourself.”
....Albert Schweitzer
A TRIANGULAR GLAND, WHICH HAS BOTH EXOCRINE AND ENDOCRINE CELLS, LOCATED BEHIND THE STOMACHACINAR CELLS PRODUCE AN ENZYME-RICH JUICE USED FOR DIGESTION (EXOCRINE PRODUCT)PANCREATIC ISLETS (ISLETS OF LANGERHANS) PRODUCE HORMONES INVOLVED IN REGULATING FUEL STORAGE AND USE.
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
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!
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
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
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.
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.
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
2. Dermatologist
Disorder of
Hair Growth,
Acne
Fertility problem
Menstrual
dysfunctionGynecologist
Obesity problem
Risk of DM II
Risk of CVS
disorderInternist
General
practitioner
?
PREVALANCE:
5-10% IN 20-40 YR
FEMALES
2
5. Insulin Receptor
• Insulin receptor (IR)is a
transmembrane receptor encoded
by a single gene (INSR gene;
Chromosome 19), belonging to
the large class of tyrosine kinase
receptors
• It is activated by INSULIN,
Insulin Growth Factor 1 (IGF-I),
and Insulin Growth Factor 2
(IGF-II)
5
6. The main activity of the Insulin Receptors when
bound by an insulin molecule is, inducing glucose
uptake
6
7. Insulin Resistance (IR)
A decrease in insulin-dependent glucose transport at
the level of target tissues due to defects at both the insulin
receptor and/or postreceptor signaling
7
8. Some Historical Facts
1921
• Relation between Glucose intolerance &
hyperandrogenism by Archard and Thiers
• Bearded diabetic woman
1980
• PCOS & insulin resistance
8
9. Insulin Resistance (IR)
• 50-75 % 0f PCOS
• 1st diagnosed those diagnosed using NIH
• Obese > Lean
• More in young females
– Ample of pancreatic reserve
– Capable to generate a compensatory
hyperinsulinemia
9
10. Insulin Resistance (IR)
• Different from Obesity and DM Type II
• More in skeletal muscle
• Only obese PCOS – hepatic too
• Pancreatic beta cell dysfunction in those with risk of
Type II DM
• Severity of IR related to abdominal obesity even in
females with normal BMI
10
11. Insulin Resistance (IR)
• Upto 35% of PCOS women – Impaired Glucose Tolerance
• 7-10% - Type II DM
• Type II DM 6 fold more likely to have PCOS
• Not in all PCOS
• Rotterdam with normal cycle – metabolically normal
• May be modifying factor rather than causative
11
14. Insulin resistance (IR)
• IR has recently been associated with increased levels of
inflammatory mediators in the blood
• Now considered to be an inflammatory disorder
• Associated with an increased incidence of cardiovascular disease
and atherosclerosis
• Thus, a risk factor for miscarriages in PCOS
14
15. Pathophysiology of IR
• Two distinct pathways
phosphotidyl-inositol 3-kinase (PI-3K)pathway
– metabolic effects
Mitogen activated protien kinase (MAPK
pathway – proliferative actions
• Insulin binding to receptor – conformational changes – tyrosine
phosphorylation of receptor & protien substrate – which binds
and serially activate PI-3K and Akt
• Akt – translocation of glucose transporter 4 (GLUT 4) from
intracellular compartment to plasma membrane – increase
glucose uptake
15
18. Pathophysiology of IR
• PSOC – selective increase in insulin activation of MAPK pathway And resistance in PI-3K pathway
• Defect early in the post-receptor signaling pathway
• Number and affinity of insulin receptors – not decreased
• Constitutive increase in phosphorylation of serine residues & decrease in insulin-stimulated
phosphorylation of tyrosine residues
• Serine phosphorylation of insulin receptor substrate prevents their binding to PI-3K and thereby
inhibits insulin signaling
• Serine phosphorylation can be induced by intracellular metabolites of free fatty acids
18
19. Pregnancy & hyperinsulinemia
• Premature granulosa cells luteinization
• Paracrine dysregulation of growth factor may disrupt
intrafollicular environment
• Alter granulosa cell – oocyte interaction and impair
cytoplasmic and/or nuclear maturation of oocyte
19
20. Diagnosis of IR
ASRM
• 75 gm OGTT
• 0 and 2 hr
• High risk
a. Hyperandrogenism with anovulation
b. Acanthosis Nigricans
c. Obesity – BMI >30kg/m2
Asian >25kg/m2
d. Family history of Type II DM & GDM
20
21. Management of IR
AIMS
• Improved Insulin Resistance
• Decrease Insulin Concentration
• Improve Hyperandrogenism, Metabolic
Alterations and Effects on fertility
21
22. Management of IR
• Lifestyle Modifications (1st choice –
ASRM; Level B)
• Insulin-Sensitising Agents
• by using antiandrogens
22
24. METFORMIN
2007
European Society for Human Reproduction and Embryology
(ESHRE)
&
American Society for Reproductive Medicine
(ASRM)
Issued Guidelines In Thessaloniki
“The use of METFORMIN should be limited to patients with
impaired glucose tolerance and should be interrupted well
before the administration of clomiphene”
Thus restricting the use of metformin to a minority of patients with
PCOS
24
25. METFORMIN
• Biguanide
• Oral hypoglycemic
• Mechanism of action
- not entirely clear
- exerts its action post-insulin receptor
- Increase Glucose uptake by insulin sensitive cells
• Metformin does not induce hyperinsulinemia and
therefore does not cause hypoglycemia (i.e. has no action
on the pancreatic β-cells).
25
26. METFORMIN
ACTIONS
• Reduces Hepatic Gluconeogenesis
• Decrease intestinal absorption of glucose
• Improves Insulin Sensitivity - increase peripheral uptake and
use of glucose by the muscles and liver.
• Increases uterine vascularization and blood perfusion
• Reduces androgen & LH levels
• Causes weight loss in some patients
26
27. METFORMIN IN PCOS
Increase
•Ovulation
•Pregnancy rates
Reduce
• Fasting Insulin Levels
(more in non-obese)
• Serum Testosterone
Concentration (modest
effect)
No Effect
•Live birth rates (alone or with
CC)
•Rate of miscarriage
•Serum lipid profiles
•Incidence of twin pregnancy
Side Effects
• Gastrointestinal (most
common)
• Lactic Acidosis (rare, but
serious)
27
Cochrane Review 2012. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women
with polycystic ovary syndrome, oligo amenorrhoea and subfertility
28. Thiazolidinediones
Selective ligands of the nuclear transcription factor
Peroxisome Proliferator - Activated Receptor Υ (PPARΥ),
which is expressed most abundantly in adipose tissue, but
is also found in pancreatic beta cells, vascular endothelium
and macrophages
28
29. Thiazolidinediones
Two Mechanisms
Directly - ‘Fatty Acid Steal’ Hypothesis
Promote Fatty Acid Uptake And Storage In Adipose Tissue
↓
Increase Adipose-tissue Mass
↓
Spare Other Insulin Sensitive Tissues And Possibly
Pancreatic Beta Cells
(from the harmful metabolic effects of high concentrations
of free fatty acids)
29
30. Thiazolidinediones
Indirectly
• Increasing the expression of adiponectin
(an adipocytokine with an insulin sensitivity effect)
• Probably by decreasing action of enzymes involved in
androgen synthesis
• Enhances insulin action in the skeletal muscle, liver and
adipose tissue - decrease peripheral insulin resistance
30
Cochrane Review 2012. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with
polycystic ovary syndrome, oligo amenorrhoea and subfertility
32. Thiazolidinediones
• Troglitazone was the first drug of this class to be studied
• Withdrawn from the market in 2000 due to Hepatotoxicity
• Only few recent studies are available using Rosiglitazone
and Pioglitazone.
32
33. Rosiglitazone
• Improve insulin sensitivity
• Improve the ovulation rate
• Decrease androgen levels
• Improve menstrual pattern
• Increases BMI
33
Cochrane Review 2012. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women
with polycystic ovary syndrome, oligo amenorrhoea and subfertility
34. Pioglitazone
• Improved the menstrual pattern
• No effects
a. anthropometric outcomes
b. endocrine outcomes (testosterone,
c. SHBG or metabolic outcomes (fasting insulin)
Cochrane Review 2012. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for
women with polycystic ovary syndrome, oligo amenorrhoea and subfertility
• FDA category C
• Bladder cancer (recent FDA advisory)
34
35. Inositols
• INOSITOLS - family of nine stereoisomers that belong to
the polyols family
• Vitamine B complex Family (Vit.B8)
35
36. Inositols
• Most relevent – Myoinositol (MYO) & D-Chiro Inositol (DCI)
• Both inositols are incorporated intracellularly into inositolphosphoglycans
(IPGs) – second messanger for insulin
• MYO being 99% of inositol
• Its reduction is important in pathogenesis of PCOS
• MYO & DCI – key role in controlling glucose homeostasis
• MYO →DCI by Epimerase
• Epimerase activated by insulin
36
37. Inositols
• MYO –IPGs mediate glucose uptake at cellular level
• DCI-IPGs mediate glycogen synthesis
• Cells with high glucose consumption has high MYO-IPGs
(brain, heart)
• DCI – mainly in glucose storage cells (liver, muscle & fat)
37
38. Inositols
• Myoinositol found naturally in many foods items - fruits, nuts and beans
• Serum concentrations - high during fetal life
- later on falls
(periconceptional periods
polycystic ovarian syndrome)
• An important constituent of the follicular microenvironment
• Play a key role in the nuclear and cytoplasmic oocyte’s development
• Higher concentrations of myoinositol in human follicular fluid provide a
marker of good-quality oocytes
• Unfer et al. Effects of Inositol(s) in Women with PCOS: A Systematic Review of
Randomized Controlled Trials. International Journal of Endocrinology 2016.
38
39. Inositols
• Observation – DCI-IPGs concentration in muscle cells &
DCI in urine of T2DM pt are lower than normal, but DCI is
increased in follicular fluid of insulin-resistant patient
• IR doesn’t effect all the cells of the body
• Infact Ovary never become insulin resistance
39
40. Inositols
Insulin resistance derived hyperinsulinemia
↓
Increase in epimerase conversion activity
↓
Increase DCI concentration into the ovary
↓
Drastic decrease in MYO concentration intracellularly
↓
Altered ovarian function
40
41. MYO:DCI
• Normal woman 100:1
• PCOS 0.2:1
• Physiological 40:1
• Combination – More physiological
Faster normalisation of insulin and glucose
response to OGTT
• Reduce cardiovascular risk of overweight insulin resistance
PCOS pt – by improving lipid profile
41
42. Inositols
• MYO to women undergoing IVF – reduce amount of rFSH
used, improving oocyte and embryo quality as well as
implantation rate
Simi et al. Inositol and In Vitro Fertilization with Embryo Transfer.
International Journal of Endocrinology. 2017
• MYO supplementation to PCOS women – restore
Spontaneous ovulation and menstrual cycles
Increase progesterone level in luteal phase
Decrease total and free testosterone
42
43. Inositols
• DCI administration is associated with improvement in IR after 8
weeks of treatment
• Recovering ovulatory function
• Reducing androgen levels & plasma TG level
• Increase SHBG level
• However, Recent Studies Outlined That Use Of DCI Seems To
Be Detrimental To The Quality Of Oocytes And Ovarian
Response To FSH Stimulation, In Non Obese Non PCOS
Women
43
44. D-chiro-inositol
• Did not improve ovulation rate the inadequate number of
studies
• Did not have any effects on BMI, waist-hip ratio or blood
pressure.
• Did not have any effects on- testosterone
SHBG
fasting glucose
fasting insulin
lipids profile
44
45. ASRM/ESHRE
Metformin in anovulatory PCOS
• No benefit in fertility or live birth rates
• Use not recommended (level A)
• No effect on miscarriage risk when given before pregnancy
• No effect on decreasing pregnancy complication or fetal wieght
45
Consensus aspects of on women,s health aspects of PCOS: the Amsterdam ESHRE/ASRM - sponsored 3rd PCOS
consensus workshop group 2012
46. RCOG
2008
Metformin alone / with CC – no benefit in
ovulation induction in PCOS
Metformin therapy for the management of infertility in women with Polycstic Ovary
Syndrome. Scientific paper no. 13. 2008
46
47. COCHRANE 2012
• Insulin-sensitising drugs - metformin, rosiglitazone,
pioglitazone and D-chiro-inositol
• Either alone or in combination with drugs to induce
ovulation (for example clomiphene citrate)
• Does not increase the chance of having a live birth
• Cochrane Review 2012. Insulin-sensitising drugs (metformin, rosiglitazone,
pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo
amenorrhoea and subfertility
47
48. COCHRANE 2014
• Metformin before or dering IVF
• Increase Clinical Pregnancy Rate and decrease OHSS
• Doesn’t increase Live Birth Rate
48
49. Clinical practice guidelines
endocrine society
2013
Recommendation
• Metformin - For PCOS Plus T2DM And IGT - who fail life
style modification
• 2nd line for Menstual Irregularity for those who can’t
tolerate Hormonal Contraceptives
• Adjuvant for prevention of OHSS in females with PCOS
undergoing IVF
49
50. Clinical practice guidelines
endocrine society
2013
• Against the use of metformin
1st line treatment of –
Cutaneous manifestion
Prevention of pregnancy complication
Treatment of obesity
Hirsutism
• Against insulin sensitizers
Inositols – due to lack of benefits
Thiozolidinedione – safety concern
50
51. INDIAN PCOS SOCIETY
2015
• Metformin is not recommended as first-line therapy for the management of
menstrual irregularity (Grade A, EL 4)
• Due to limited evidence on use of metformin in adolescents without
established glucose intolerance- recommends against its use in adolescents
with PCOS
• Lifestyle modification is better than metformin in improving
hyperandrogenism, obesity and signs of IR
• Therefore, recommends lifestyle modification as first-line therapy followed by
metformin in adolescents and children
• Metformin should be initiated in children only after a wait-period of two years
post-menarche
• PCOS Guideline 2015. Management of Polycystic Ovary Syndrome in India.
51
52. INDIAN PCOS SOCIETY
2015
• In women with PCOS, it is recommended not to use
metformin therapy only during pregnancy until specific
evidence on beneficial effects is demonstrated (Grade B,
EL 3)
• Due to insufficient evidence, alternative (acupuncture)
and complementary therapeutic options (e.g. myoinositol,
omega-3 fatty acids) are not recommended for the
management of hyperandrogenism (Grade B, EL 4)
• PCOS Guideline 2015. Management of Polycystic Ovary Syndrome in India.
52
53. N ACETYL CYSTEINE
• Acetylated variant of amino acid L-Cystiene
• Commonly used safe mucolytic drug
• Increases the cellular levels of antioxidant and reduces
glutathione at higher doses.
• Convert proinsulin to insulin
• Therefore, NAC has a potential to improve insulin receptor
activity in human erythrocytes and improve insulin secretion
in response to glucose
• Thakker et al. N-Acetylcysteine for Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized
Controlled Clinical Trials. Obstetrics and Gynecology International. 2015
53
54. N ACETYL CYSTEINE
• Significant improvement in pregnancy and ovulation rate
in the studies with short-term outcomes compared to
placebo
• Limitations of existing studies such as poor quality, less
studies assessing live-birth rates
• Well-designed randomized-controlled trials should
conducted
54