Update on LETROZOLE Current Guidelines for Ovulation Induction Dr. Sharda Jain Lifecare Centre
Update on LETROZOLE Current Guidelines for Ovulation Induction
LET NOT FORGET
WHY
??
LETROZOLE was withdrawn from
Indian market (2012)
“SAFETY ISSUES”
“Could Be Teratogenic In Human”?
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
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.
Update on LETROZOLE Current Guidelines for Ovulation Induction Dr. Sharda Jain Lifecare Centre
Update on LETROZOLE Current Guidelines for Ovulation Induction
LET NOT FORGET
WHY
??
LETROZOLE was withdrawn from
Indian market (2012)
“SAFETY ISSUES”
“Could Be Teratogenic In Human”?
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
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.
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 .
The method of ovulation induction selected by the clinician should be based upon the underlying cause of anovulation and the efficacy, costs, risks, burden of treatment, and potential complications associated with each method as they apply to the individual woman. In this presentation I have mentioned every points in detail.
Vasundhara Hospital Jaipur is a premier specialty hospital for infertile couples, complete women care, high risk pregnancy management, located in heart of Jaipur.
Click to more info :- https://www.vasundharafertility.com/jaipur
Ovarian reserve refers to the reproductive potential left within a woman's two ovaries based on number and quality of eggs. Diminished ovarian reserve is the loss of normal reproductive potential in the ovaries due to a lower count or quality of the remaining eggs
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 .
The method of ovulation induction selected by the clinician should be based upon the underlying cause of anovulation and the efficacy, costs, risks, burden of treatment, and potential complications associated with each method as they apply to the individual woman. In this presentation I have mentioned every points in detail.
Vasundhara Hospital Jaipur is a premier specialty hospital for infertile couples, complete women care, high risk pregnancy management, located in heart of Jaipur.
Click to more info :- https://www.vasundharafertility.com/jaipur
Ovarian reserve refers to the reproductive potential left within a woman's two ovaries based on number and quality of eggs. Diminished ovarian reserve is the loss of normal reproductive potential in the ovaries due to a lower count or quality of the remaining eggs
PCOD,How are they different ??Difficulties & Solutions made Easy , Dr. Sharda...Lifecare Centre
Tremendous advances and extensive human studies have uncovered the complexity and management of PCOD
Global prevalence -2.2% to 26% Roughly 1 in 15 women worldwide, (Lancet, 2007)
Ovarian Hyperstimulation in Intrauterine InseminationElmar Breitbach
Intrauterine insemination is well established in the treatment of infertility. But which pretreatment leads to the best results? Do we have to trigger ovulation? What about luteal phase support? Whar patients do have the best chances? When do we have to switch to IVF?
Evidence based answers to these questions an a bit of experience based suggestions.
Explore the intricacies of ovulation induction in intrauterine insemination (IUI) with Dr Laxmi Shrikhande's informative slide share presentation. From understanding the hormonal mechanisms to the latest techniques, this presentation offers insights into optimizing fertility through IUI. Whether you're a clinician seeking to enhance patient outcomes or an individual navigating fertility treatments, this resource provides valuable knowledge for your journey towards conception.
Do Women With Polycystic Morphology Without Any Other Features of PCOS Benefi...Alex Swanton
Women with ovaries of polycystic morphology (PCO), without any other features of polycystic ovary syndrome(PCOS), respond similarly to women with PCOS when stimulated with exogenous gonadotrophins, and both groups share various endocrinological disturbances underlying their pathology.
Invited lecture by Dr Sujoy Dasgupta in the Webinar on “PCOS Advocacy” by Endocrinology Committee of FOGSI (Federation of Obstetric and Gynaecological Societies of India), held in September, 2020
medical management of infertility,think before surgery!!!!ShitalSavaliya1
Nowdays infertility is major issues world wide,It covers both male and female infertility causes,investigation and related treatments.it also includes recent options available at infertility centres.
“Inheritance” in images, from Darwin’s “tree of life” to DNA’s iconic crystallography to the epigenetic dynamicsHowever, the script needs to be interpreted and receives meaning only from the interplay with the environment
THE ASSISTED REPRODUCTION TECHNOLOGY REGULATION RULES, 2010
Members of drafting committee11 members
1- Sr Advocate Supreme Court of India
2 – Public Interest Legal Support and Research
3 – Dept of Family Welfare, M of Fam Wel and Research
5 – experts from the field of Reproductive Medicine
Ovarian Drilling Do's & Don'ts - By Dhorepatil BharatiBharati Dhorepatil
Rotterdam Criteria 2003
The Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group
March 2–3, 2007, Thessaloniki, Greece.
Human Reproduction 2008
Luteal Phase - Clinical Point of View - By Dr Dhorepatil BharatiBharati Dhorepatil
Maintenance of pregnancy
Corpus luteum Progesterone
After ovulation ~ during the early first trimester ~ until placental function established
Removal of the corpus luteum spontaneous pregnancy loss
Ovarian progesterone production implantation & early pregnancy
Role of decreased androgens in the ovarian response to stimulation in older women
Part I: Effects of testosterone (T) on preantral and antral follicles
Part II: How to improve ovarian response ?
Exogenous testosterone
DHEA
Aromatase inhibition (AI)
LH/HCG
Growth hormone (GH) / IGF-I
Indivisualization of Ovulation Induction - Dr Dhorepatil BharatiBharati Dhorepatil
IVF started to develop fast with the aim of maximizing pregnancy rates per cycle
Higher number of oocytes and thus more embryos
Use of unphysiological high doses of gonadotropins
Time consuming protocols
Higher costs
Patient discomfort
Higher risk of OHSS
Very high risk of multiple gestation
MONITORING PITUITARY DOWN-REGULATION
If GnRH Agonist is started in the late luteal phase a menstrual bleeding normally indicates that the estrogen is low and FSH can be started.
Blood tests will clearly confirm down-regulation – ovarian/pituitary hormones.
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
Ovulation Induction - Simplified - Dr Dhorepatil BharatiBharati Dhorepatil
What are factors to be considered
Ovarian reserve
Previous ovarian response
Basic hormone profile
Role of FSH & LH
Trigger
Luteal phase support
Pregnancy rate/cycle
Ovarian reserve tests provide an indirect measure of the cohort of recruitable antral follicles present in the FSH window at the beginning of each menstrual cycle..Functional Ovarian Reserve
Why we need to predict?
Hormone defects may cause severe neurological, metabolic or cardiovascular consequences and lead to the early onset of osteoporosis
Psychological Depression
Low levels of self esteem and Life satisfaction
Sexual Dysfunction
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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.
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
- 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
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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
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.
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
4. PCOS
• Heterogeneous, reproductive-metabolic,pathological disorder
• Primary cause: Ovarian androgen overproduction
• Associated with insulin resistance and obesity
1. Allahabadia GN et al. Polycystic Ovary Syndrome in the Indian
Subcontinent. Semin Reprod Med 2008;26:22–34.
2. Badawy A et al. Treatment options for polycystic ovary syndrome. Inter J
Women’s Health 2011:3 25–35
3. Malik et al. Management of Polycystic Ovary Syndrome in India. Fertility
Science & Research. Jan-Jun 2014; 1(1): 23-4
Major symptoms
• Menstrual disorders
• Hyperandrogenaemia
• Metabolic syndrome
• Infertility
Dr.Bharati Dhorepatil Ferticon2017
4
5. • 31yrs old, married 7yrs, wt 50.5, BMI 23.37
• Semen parameter..80 millions,80% motility
• Hormonal Parameters…FSH 6.82,LH 13.45,TSH
0.64,Prolactin 16ng/ml, Free Testesteron 45.72,
AMH 13ng/ml
• TVS findings…PCOM…with Rt AFC 20 and Lt.25
follicles
• Clinical side.. H/0 irregular cycles.(3 to 4 /yrs)
Acne gr III, Hirsutism FG Score 8
Dr.Bharati Dhorepatil Ferticon2017 5
9. Dr.Bharati Dhorepatil Ferticon2017 9
Two Patterns are seem most commonly…
1.Peripheral Cystic Pattern
2.General Cystic Pattern
2 to 8 mm 8to 10 mm
10. • General cystic pattern is associated with an
ovarian steroidogenesis disorder whereas
• The peripheral cystic pattern is associated
with abnormal gonadotropin secretion
Ultrasound Obstet Gynecol 1998;11:332–336
Dr.Bharati Dhorepatil Ferticon2017 10
11. • Hypersecretion of LH during the follicular phase of the
menstrual cycle in PCOS is associated with hyperplasia
of the ovarian theca and stromal cells.
• Increased vascularity has been demonstrated by color
Doppler imaging and pulsed Doppler spectral analysis
within the ovary probably because of Elevated LH
levels may be responsible for increased stromal
vascularization by influencing neoangiogenesis,
catecholaminergic stimulation and leukocyte and
cytokine activation
Dr.Bharati Dhorepatil Ferticon2017 11
15. Why Abnormal Response of polycystic ovary to COS?
Extremely difficult to find GT threshold
Recruitable pool of follicles is increased
Stromal hyperplasia contributes to larger than normal amounts
of androgens to the follicular microenvironment
Granulosa cell aromatase activity is normally decreased
however, it is readily stimulated by exogenous FSH
Follicular response initially slow, but explosive at later stages
of stimulation
Dr.Bharati Dhorepatil Ferticon2017 15
16. Could we elaborate ovulation induction
protocols in PCOS ?
What is your first line of treatment ?
16
17. The management of anovulatory infertility in women with PCOS: an
analysis of the evidence to support the development of global WHO
guidance.
• Management includes lifestyle changes, bariatric surgery,
pharmacotherapy (including clomiphene citrate (CC),
aromatase inhibitors, metformin and gonadotropins), as
well as laparoscopic surgery.
• CC should be first-line pharmacotherapy for ovulation induction and
letrozole can also be used as first-line therapy.
• Metformin alone has limited benefits in improving live birth rates.
• Gonadotropins and laparoscopic surgery can be used as second-line
treatment. There is no clear evidence for efficacy of acupuncture or
herbal mixtures in women with PCOS.
failed.
Dr.Bharati Dhorepatil Ferticon2017 17
18. • Can we individualize CC or letrozole or
gonadotrophins depend on E2 levels Low &
high…
• Low E2..Responds well with CC or
Gonadotrophins
• High E2 ..responds well with letrozole
Dr.Bharati Dhorepatil Ferticon2017 18
19. FSH 2.5
E2 55
LH 7
AMH 4
AFC 15..P P
FSH 6.5
E2 25
LH 10
AMH 3.5
AFC 15..C P
FSH 2.5
E2 45
LH 2
AMH 10
AFC 25..C P
FSH 4.1
E2 75
LH 7
AMH 7.5
AFC 18..P P
19
20. What modifications of Clomiphene
protocols can be done to improve
outcomes?
Or
Would you shift to aromatse inhibitor as a
first line option or only after CC faliure?
20
21. Luteal phase clomiphene citrate for ovulation
induction in women with PCOS.
• Patients in Group 1 received 100 mg of CC daily for 5 days starting on day 5 of
menses, and patients in Group 2 received 100 mg of CC daily for 5 days starting the
next day after finishing medroxyprogesterone acetate (MPA) (before withdrawal
bleeding).
RESULTS:
• The total number of follicles and the number of follicles ≥14 mm during stimulation
were significantly greater in Group 2. The endometrial thickness at the time of
(hCG) administration was significantly greater in Group 2 as compared to Group 1.
Pregnancy occurred in 10.3 % in Group 2 and in 8.7 % in Group 1.
CONCLUSION:
Luteal phase administration of CC in patients with PCOS leads to increased follicular
growth and endometrial thickness, which might result in a higher pregnancy rate.
Kosar O1 Arch Gynecol Obstet. 2014 Oct
Dr.Bharati Dhorepatil Ferticon2017 21
22. Clomiphene citrate 'stair-step' protocol vs. traditional protocol in
patients with PCOS: a RCT
• In the stair-step protocol,patients were treated with CC 50 mg/day for 5 days and
then in nonresponsive patients, the dosage was increased to 100 mg/day for
5 days in the same cycle. Patients who failed with 50 mg/day CC in the previous
cycle were stimulated with 100 mg/day CC and were the control group.
• Ovulation and pregnancy rates were similar between the stair-step and the
control group (43.3 vs. 33.3 %, respectively) (16.7 vs. 10 %, respectively). The
duration of treatment was significantly shorter in stair-step compared to
traditional protocol (20.5 ± 2.0 vs. 48.6 ± 2.4 days, respectively). Uterine side
effects were evaluated with endometrial thickness and uterine artery Doppler
ultrasound; no significant differences were observed.
CONCLUSIONS:
• The stair-step protocol has a significantly shorter treatment period without any
detrimental effect on the ovulation and pregnancy rates.
Deveci CD Arch Gynecol Obstet.2015 Jan
Dr.Bharati Dhorepatil Ferticon2017
22
23. Case
• 31yrs old, married 7yrs, wt 50.5, BMI 23.37
• Semen parameter..80 millions,80%
• Hormonal Parameters…FSH 6.82,LH 13.45,TSH 0.64,Prolactin
16ng/ml, Free Testesteron 45.72, AMH 13
• USG findings…PCOM.with 20 and 25 follicles on either side
• Clinical side.. H/0 irregular cycles.(3 to 4 /yrs)
Acne gr III, Hirsutism FG Score 8
• Undergone Laparoscopy,Hyestroscopy,Ov.Drilling
• Treatment H/O…she has been received 16 cycles of various
drug regimes like CC,CC+HMG,HMG,FSH with no follicular
growth
• Past h/o of treatment 5yrs back with some oral medication
good response?
Dr.Bharati Dhorepatil Ferticon2017 23
24. • Do you face any group of patients difficulty in
using letrozole?
Dr.Bharati Dhorepatil Ferticon2017 24
25. Estradiol Levels..
• Estradiol levels donot correspond with
maturity of the follicle on the day of HCG….
Lower S.E2 levels
• Thin pts..where levels of E2 already low..
D8-10..leads breakthrough bleeding..
Our unpublished data of 50 pts with BMI 19.5,in
CC resistance group
Dr.Bharati Dhorepatil Ferticon2017 25
27. There is a lot of controversy on the role of Insulin
sensitizers in PCOS patients. Do you still use
metformin ?
27
28. Lifestyle modification should be the first-line treatment.
• Current evidence - metformin cannot be recommended as first-line
pharmacological treatment for anovulatory infertile women with PCOS.
• Clomiphene citrate still represents the gold standard first line theraphy
• Metformin does not improve the efficacy of clomiphene citrate as a first-step
treatment for ovulation induction in anovulatory infertile women with PCOS.
• Available evidence is insufficient to recommend metformin as a primary treatment
in non-obese PCOS subgroup.
• Metformin plus clomiphene citrate could be considered an effective option in
patients with CCR-PCOS.
• More attempts with metformin plus clomiphene citrate are warranted when there
is limited access to gonadotrophins.
RBM online 2016
28
29. In patients with CCR-PCOS undergoing ovulation induction with
gonadotrophins, the addition of metformin increases the rates of clinical
pregnancy and live birth and reduces the cancellation rate.
In patients with PCOS undergoing assisted reproduction technniques,
metformin co-treatment reduces the OHSS risk and increases the pregnancy
rate.
No evidence exists of reduced spontaneous abortion risk in women with PCOS
who have undergone pre-gestational metformin tretment.
No evidence exists of increased risk of major anomalies in women with PCOS
undergoing metformin treamtent during the first trimester.
Adequately powered RCT are needed to evaluate the efficacy of metformin
treatment in different PCOS phenotypes.
RBM online 2016
29
30. There is a lot of discussion on myoinositol
nowdays. What is your experience with the
drug ?
30
31. Clinical evidences with Myoinositol in PCOS
Free & Serum
Testosterone
Myoinositol
IR
Insulin
Sensitivity
Provides Good
quality
Oocytes
Improve
glucose
utilization
Restores
Menstruation &
Normal Ovulation
Improves
pregnancy rates
31
32. Inositol's and other nutraceuticals' synergistic actions counteract
insulin resistance in polycystic ovarian syndrome and metabolic
syndrome: state-of-the-art and future perspectives.
• MI and DCI have been classified as insulin-sensitizers and seem to
adequately counteract several InsR-related metabolic alterations with a
safe nutraceutical profile.
•
• Supplementation with MI and/or DCI complement each other in their
metabolic actions and act in synergy with other insulin sensitizing drugs
and/or nutraceuticals.
• Considering the possible bias due to different methodologies across
published studies, we conclude that there is a need for further studies on
larger cohorts and with greater statistical power.
Paul C, et al, Gynecol Endocrinol. 2016 Jun
Dr.Bharati Dhorepatil Ferticon2017 32
33. Ovulation induction with myo-inositol alone and in combination
with clomiphene citrate in PCOS patients with insulin resistance.
50 anovulatory PCOS patients with insulin resistance. All of them received myo-
inositol during 3 cycles. If patients remained anovulatory or no pregnancy was
achieved, combination of myo-inositol and clomiphene citrate was used in the
next 3 cycles.
RESULTS:
After myo-inositol treatment, ovulation was present in 61.7% and 38.3% were
resistant. Of the ovulatory women, 37.9% became pregnant. Of the 18 myo-
inositol resistant patients after clomiphene treatment, 13 (72.2%) ovulated. Of
the 13 ovulatory women, 6 (42.6%) became pregnant.
CONCLUSION:
Myo-inositol treatment ameliorates insulin resistance
and body weight, and improves ovarian activity in PCOS
patients.
Kamenov Z Gynecol Endocrinol. 2015 Feb
Dr.Bharati Dhorepatil Ferticon2017 33
34. When giving Gonadotropins for COS :
Which Gonadotropin do you use ? Does the type
make a difference
34
35. Can we predict Starting Dose for the stimulation
in IUI or IVF cycle
AGE & AMH,FSH
AGE & AFC,FSH
35
36. Individualization of OI according to AMH
• Starting Dose
• Maintanence Dose
• Trigger
Dr.Bharati Dhorepatil Ferticon2017 36
37. Which Gonadotrophin to use?
HMG / FSH / Rec FSH
FSHHMG when combining with CC
FSHHMG in standard ovulatory IUI /COH
HMG in Hypogonadotrophic hypogonadism
HMG in patients with high FSH
FSH in patients with high LH (PCOS)
37
38. Comparison between stimulation with highly purified hMG
or recombinant FSH in patients undergoing IVF with GnRH
antagonist protocol.
• Retrospective study : N= 508 cycles
• 320 rFSH , 188 – hp/hmg
• rFSH – had more mature oocytes, more embryoes with
lower dose of Gn
• In subgroup analysis – young pts in rFSH group had better
cyvle outcomes
Conclusion – In antagonist protocol, different gonadotropin
products are equally effective. The choice of one or the
other should depend on the availability, convenience of
use, and cost.
Shavit T, et al, Gynecol Endocrinol. 2016 Mar
Dr.Bharati Dhorepatil Ferticon2017 38
39. When giving Gonadotropins for COS :
What protocol do you use ?
What is your opinion on using
Clomiphene in IVF cycles?
40. Gonadotrophin Induction
• CC+HMG/FSH
• HMG/FSH
– Standard regime
– Step-up regime
– Chronic low dose step up regime
– Step down regime
• GnRh antagonist+HMG/FSH
40
41. At what stage would you abort or
convert an IUI cycle into IVF cycle ?
3,4 ,5 or more mature follicles?
41
42. Is it necessary to wait for menses
before starting ovarian
stimulation?
42
43. ORPI= AMH (ng/ml) x AFC (2-9 m) and the result was divided by the age
(years) of the patient
ORPI Values Oocyte No expected Protocol
< 0.2 < 3 GnrH Antagonist, Short
GnrHa, CC + Gnrha long
> 0.2 < 0.5 4 - 5 Gnrh antagonist, short
Gnrh, Long Gnrha
0.5 < 0.9 6 – 14 Long Gnrha, Gnrh
Antagonist
0.9 >15 Gnrh Antagonist
Ovarian response prediction index (ORPI) implications for
individualised COS.
Oliveira, et al, reprod biol endocrinol 2012.
43
44. Gonadotrophin-releasing hormone antagonists for assisted
reproductive technology.
• There is moderate quality evidence that the use of GnRH
antagonist compared with long-course GnRH agonist protocols is
associated with a substantial reduction in OHSS without reducing
the likelihood of achieving live birth.
Al-Inany HG, et al, Cochrane Database Syst Rev. 2016 Apr
Dr.Bharati Dhorepatil Ferticon2017 44
46. Effect of GnRH antagonists on CPR with gonadotropins in IUI
No significant improvement in clinical pregnancy rates
when GnRH antagonists were used during COH + IUI
cycles, despite a significant increase in the number of
follicles > 16 mm on the HCG trigger day.
Ramazan Dansuk, et al, Singapore Med J. 2015 Jun
46
47. How do you monitor these cycles ?
Hormones / Usg Scan / Doppler
47
48. Monitoring starts..
• D7,D8,D9…any day could be a start in IUI cycle if
IVF D5
• Growth pattern to be followed..Day X 2mm
appro.
• Alternate day monitoring is advisable if required
changed according to the need
• Sustained growth…is must
In healthy follicles, genes direct
cytodifferentiation, proliferation, and follicular fluid
formation.
48Dr.Bharati Dhorepatil Ferticon2017
49. What to achieve before ovulation?
49Dr.Bharati Dhorepatil Ferticon2017
50. • The large increase in LH inhibits androgen
production, and as a result estradiol
concentrations decrease drastically from the
preovulatory peak.
• Granulosa cells become 'luteinized', and
consequently a small preovulatory rise in
progesterone occurs within one hour of the LH
surge completion
50Dr.Bharati Dhorepatil Ferticon2017
51. Hormonal Cycles:
LH, FSH, Estradiol,
Progesterone, Inhibin
A & B
europe.obgyn.net/nederland/mp/o
vergang/images/overgang14x.gif
After a248.e.akamai.net/.../pubs/mmanual_home/ illus/i232_1.gif
Dr.Bharati Dhorepatil Ferticon2017 51
52. 52
•Assesment of the follicular maturity and endo receptivity
and the time of HCG Is one of the Key factors for the
success of all ART procedures
•Vascular changes are the reflection of the biochemical
changes.
•3D power doppler gives not only qualitative but also
quantitaive idea of the global vasularity
Dr.Bharati Dhorepatil Ferticon2017
53. When to give HCG..
• Triple line Endo >7mm,follicle >17mm
• Perifollicular and subendometrial Hallo…oedema
• Cumulus presence..30-40%
• Follicular volume..0.6 to 1.5ml
• Flow Indices…PSV: >10,RI:<0.5
• Perifollicular Vasularity..3/4th
• Sub Endo vasularity..minimum 5 spiral vessels
reaching to zone 4,ant & post,RI<0.6
• Endo peristalsis 3to5/ min
• Uterine A..on dominent sidePI:<3.2
53Dr.Bharati Dhorepatil Ferticon2017
54. Timeline of ovulation
• Case A..Day 11…DF..18mm,..endo..8mm,triple
line
• but RI<0.48,PSV 6-7,poor flow
Timeline…Wait…HCG next Day or when
parameters improves as PSV low
54
56. Laparoscopic drilling by diathermy or laser for ovulation
induction in anovulatory PCOS
25 RCT’s
Noevidence of a significant difference in rates of
a) clinical pregnancy,
b) live birth or
c) miscarriage in women with clomiphene-resistant PCOS
undergoing LOD compared to other medical treatments.
The reduction in multiple pregnancy rates in women undergoing LOD
makes this option attractive.
However, there are ongoing concerns about the long-term effects of
LOD on ovarian function.
Farquhar C, Cochrane Database Syst Rev.2012 Jun
56
57. Drilling: medical indications and surgical
technique.
• Laparoscopic drilling is indicated for patients with polycystic ovary
syndrome with ovulatory resistance to the use of clomiphene
citrate, body mass index less than 30 kg/m2 and preoperative
luteinizing hormone above 10 IU/L & AMH >6 to <10
• The preferred surgical technique should be the realization of 5 to
10 perforations on the surface of each ovary bilaterally using
monopolar energy.
• Hueb CK, et al, Rev Assoc Med Bras (1992). 2015 Nov-Dec
Dr.Bharati Dhorepatil Ferticon2017 57
58. What about the risks of COS – multiple
pregnancy and OHSS. What precautions
do you take ?
58
59. Strategies to prevent OHSS
Identify high responders.
Titration of COS.
Monitor the ovarian response carefully.
If more than 5 follicles - abort cycle or convert to
IVF.
Use GnRH agonists as trigger.
Use of antagonists, Cabergoline, HES
Do not use HCG for luteal support
59
60. OHSS prevention.
The recent implementation of four new modalities:
• the GnRH antagonist protocol,
• GnRH agonist (GnRHa) triggering of ovulation,
• blastocyst transfer and
• embryo/oocyte vitrification,
• renders feasible the elimination of OHSS in connection with ovarian
hyperstimulation for IVF treatment.
Papanikolaou EG , Reprod Biol Endocrinol.2011 Nov
Dr.Bharati Dhorepatil Ferticon2017 60
61. • Conversations are pleasant,
Discussions are interesting,
Debates are productive……
• In any event, conversation, discussion, and
debate are positive.
• They can ignite people's passion, their
creativity, and bring their best ideas to the
table…..
• Thank You all for Active participation
Dr.Bharati Dhorepatil Ferticon2017 61