Vaginal and intramuscular progesterone are both effective for luteal phase support in IVF, but vaginal administration is preferred. Several studies found comparable pregnancy and live birth rates between vaginal and intramuscular progesterone. Vaginal progesterone increases endometrial tissue levels while intramuscular progesterone results in higher serum levels. However, vaginal administration has better patient compliance and fewer side effects than intramuscular injections.
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.
Evidence for a significant effect in favor of progesterone for luteal phase support. Best result with synthe7c progesterone.
• Evidence that the addi7on of othe substances such as estrogen or hCG doe not improve outcomes.
• Evidence for equivalence of IM and vaginal routes of administra7on. Vaginal route is best tolerated by pa7ents.
• hCG, or hCG plus progesterone, was associated with a higher risk of OHSS. The use of hCG should therefore be avoided.
• Evidence showing a benefit from the addi7on of GnRH agonist to progesterone in luteal phase support
Progesterone for luteal phase support in IVF cyclesHesham Al-Inany
Luteal phase support is essential for IVF cycles. Progesterone has many forms and modalities: which to use? this talk is an attempt to answer this question
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
Evidence for a significant effect in favor of progesterone for luteal phase support. Best result with synthe7c progesterone.
• Evidence that the addi7on of othe substances such as estrogen or hCG doe not improve outcomes.
• Evidence for equivalence of IM and vaginal routes of administra7on. Vaginal route is best tolerated by pa7ents.
• hCG, or hCG plus progesterone, was associated with a higher risk of OHSS. The use of hCG should therefore be avoided.
• Evidence showing a benefit from the addi7on of GnRH agonist to progesterone in luteal phase support
Progesterone for luteal phase support in IVF cyclesHesham Al-Inany
Luteal phase support is essential for IVF cycles. Progesterone has many forms and modalities: which to use? this talk is an attempt to answer this question
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 adjuvants in poor ovarian responders , undergoing infertility treatment , in terms of Intra uterine inseminations ( IUI ) to In Vitro Fertilization ( IVF )
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.
LUTEAL PHASE SUPPORT CHOOSING THE RIGHT PROGESTERONEDr. Girija Wagh
Increasing maternal age, need for assited reproduction also has increased the need for appropriate luteal phase support During the luteal phase of the menstrual cycle, progesterone plays a crucial role in preparing the uterine lining for potential embryo implantation. In assisted reproductive technologies (ART) and fertility treatments, optimizing luteal phase support is essential for successful outcomesAdministering exogenous (external) progesterone during the luteal phase is associated with significantly higher pregnancy rates compared to placebo or no treatmentWomen undergoing ART are appropriate candidates for luteal phase supportchoosing the right progesterone for luteal phase support is critical for optimizing fertility treatments. Collaboration among specialists ensures better outcomes for patients
Describes tThe precise dosage and duration of progesterone administration for luteal support in IVF are still topics of ongoing research, which could potentially lead to suboptimal outcomes such as miscarriage or preterm birth if not correctly managed.The efficacy of progesterone in reducing miscarriage and preterm birth rates in IVF, creating uncertainty about the best approach to luteal phase support.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
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
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.
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
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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.
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
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
3. LUTEAL PHASE SUPPORT IN IVF
“Hormone administration during the
second phase of the stimulation
cycle to support the endometrium
and improve implantation.”
4. LUTEAL PHASE SUPPORT IN IVF
➢ Is LPS of benefit for IVF patients?
➢ What is the best dose and formulations of
drugs for LPS ?
➢ Which Is superior for LPS hCG or
Progesterone?
➢ Which is the best route for administration of
progesterone for LPS ?
➢ Is it beneficial to add estrogen to
progesterone for LPS ?
➢ What are other hormones that can be
used?
➢ For how long should LPS continue after IVF ?
6. LUTEAL PHASE SUPPORT IN IVF
Is LPS of benefit for IVF patients?
✓ Elevated serum estradiol concentration
✓ Suppression of LH by continued down-
regulation by GnRH agonists
✓ hCG injection before OR
✓ Removal of of granulosa cells at OR
✓ Supra physiological E2/P4 in early luteal phase
➢ Abnormal luteal function after COS for IVF
7. LUTEAL PHASE SUPPORT IN IVF
Is LPS of benefit for IVF patients?
LPS was a requirement for optimal outcome
after IVF.
Edwards & Steptoe. (1980) Br J Obstet Gynaecol 1980; 87: 737–56,
long protocol, lead to an endocrinological
disturbance during the luteal phase.
Smitz et al. (1992) Hum Reprod 1992; 7: 1225–9.,
Smitz et al. (2001) Acta Obstet Gynecol Scand 2001;80.
Luteolysis is also initiated prematurely in
antagonist co-treated IVF cycles}
(Albano et al., 1998; Beckers et al., 2002)
9. LUTEAL PHASE SUPPORT IN IVF
Is LPS of benefit for IVF patients?
Meta-analysis of prospective, randomized
studies showed that LPS was clearly beneficial in
establishing a pregnancy after IVF, following
stimulation as part of a long protocol.
Soliman et al. (1994 ) Fertil Steril 1994
Pritts & Atwood, (2002) Hum Reprod. 2002
10. LUTEAL PHASE SUPPORT IN IVF
➢ What is the best dose and formulations of
drugs for LPS ?
11. LUTEAL PHASE SUPPORT IN IVF
➢ What is the best dose and formulations of
drugs for LPS ?
➢ There is much controversies about
➢ Type of drugs,
➢ Formulations,
➢ Doses,
➢ Combinations,
➢ Duration of treatment.
12. LUTEAL PHASE SUPPORT IN IVF
➢ What is the best dose and formulations of
drugs for LPS ?
➢ The ideal LPS needs to be
➢ Simple,
➢ Effective,
➢ Acceptable to patients.
13. LUTEAL PHASE SUPPORT IN IVF
➢ The drugs normally used for LPS are:
➢ Human chorionic gonadotropin (hCG)
➢ Progesterone
➢ Estrogen
➢ GnRH-agonists
14. LUTEAL PHASE SUPPORT IN IVF
hCG versus Progesterone
Human chorionic gonadotrophin (hCG):
Rescue corpus luteum
(Hutchins Williams et al. 1990)
Improves the implantation by increasing
relaxin, integrin & placental ptn.
(Mochtar, 1998)
Increase the risk of OHSS
(van der Linden et al., 2012)
15. LUTEAL PHASE SUPPORT IN IVF
hCG versu Progesterone
Progestagen:
➢ Improves endometrial receptivity
(Kolibianakis & Devroy, 2002)
➢ Promotes local VD and uterine musculature
quiescence by inducing nitric oxide synthesis
in decidua
(Bulletti & de Ziegler, 2005)
➢ Act as immunologic suppressant blocking Th1
and inducing release of Th2 cytokines
(Ng et al. 2002)
➢ ? value as regards miscarriage
(van der Linden et al., 2012)
16. LUTEAL PHASE SUPPORT IN IVF
hCG versus Progesterone
OutcomeComparisonStudy
PR
entirely
comparable
32.0% and 31.7%
micronized vaginal
progesterone (600
mg/day) + oral E
valerate (6 mg/day),
Versus
hCG (2000 IU on days 4, 8
and 12 of the LP
Van Steirteghem et al.
(1988)
Hum Reprod 1988
A prospective, RCT,
91 patients
PR
Comparable
(18.1% vs 17.3%
hCG (n=72), 1500 IU,
Versus
im progesterone (n=49),
25 mg/day
Claman et al. (1992)
Hum Reprod 1992
A prospective RCT
PR
36.7% vs 35.3%,
IR
12% vs 14% y .
OHSS was
higher with hCG
2000 IU hCG (n=38)
Versus
50 mg progesterone i.m.
daily (n=39).
Araujo et al. (1994) J
Assist Reprod Genet
1994
A prospective RCT,
77 patients
17. LUTEAL PHASE SUPPORT IN IVF
hCG versus Progesterone
Artini et al. J (1995) Endocrinol Invest.
Martinez et al., (2000) Gynecol Endocrinol.
Ludwig et al., (2001) Acta Obstet gynecol Scand
Ugur et al., (2001) Fertil Steril
In these studies GnRH-a long protocol was
used luteal support with hCG or intramuscular
or vaginal progesterone was used only during
luteal phase.
There was no difference in CPR, OPR, SAB.
18. LUTEAL PHASE SUPPORT IN IVF
hCG versus Progesterone
OutcomeComparisonStudy
The use of hCG led to
significantly better
implantation (19.0% vs
7.5%) and pregnancy
rates (31.4% vs 14.3%).
Due to the low
bioavailability (already
discussed in by the
authors).
Oral, micronized
progesterone (400
mg/day) versus
hCG (1500 IU)
(70 transfers in each
group),
Buvat et al. (1990)
(Fertil Steril 1990
in 171 embryo transfer
cycles.
- It was excluded from
the meta-analysis by
Soliman et al. (1994),
19. LUTEAL PHASE SUPPORT IN IVF
hCG versus Progesterone
➢ There was no difference in CPR, OPR, SAB.
➢ hCG and progesterone have the same efficacy,
but hCG has an increased OHSS risk.
➢ Progesterone should be the first choice for
luteal phase support following ovarian
stimulation in the long protocol.
21. LUTEAL PHASE SUPPORT IN IVF
Progesterone (oral route)
➢ Convenience
➢ Side effects
➢ Sedation
➢ Drowsiness
➢ Only 10% of oral dose circulates as active P4
{first pass effect}
➢ No secretory transformation in patients with
oral micronized progesterone
(Devroey et al.1989; Bourgain et al. 1990)
➢ The clinical efficacy ?
➢ Less effective
➢ More variable
22. LUTEAL PHASE SUPPORT IN IVF
Progesterone (oral route)
➢ After oral administration, progesterone is
broken down into numerous metabolites,
which have a negative effect on the (CNS)
and on the uterus.
➢ The serum levels rose briefly to 1.5 ng/ml, then
fell sharply below 0.5 ng/ml after 6 hours,
compared to 4 and 5 ng/ml for more than 24
hours after vaginal administration.
(Nahoul et al. (1993)
23. LUTEAL PHASE SUPPORT IN IVF
Progesterone (oral route)
OutcomeComparisonStudy
PR 28.8 % vs. 25%.
Ongoing PR 25.96 %
vs. 22.9%
Births per ET 23% vs.
22.2%
Non significant.
More side effects
with oral route
Oral
progesteron
e, 300
mg/day
(N=144)
Vaginal
progestero
ne gel (90
mg/day)
(N=139)
Pouly et al. (1996),
Hum Reprod 1996; 11:
2085–9.
Prospective,
randomized study
The implantation
rate 30.7%
vs.10.7%; p 0.01,
The ongoing
clinical pregnancy
rate 41.1% vs.20%
Not significant.
Oral
Utrogestan
capsules
(200 mg, 4
daily) (n=32)
Vaginal
Utrogestan
capsules
(100 mg,
twice daily)
(n=32)
Friedler et al. (2001)
Acta Obstet Gynecol
Scand, 2001;80
Prospective,
randomized male
factor infertility
24. LUTEAL PHASE SUPPORT IN IVF
Progesterone (oral route)
OutcomeComparisonStudy
The implantation
rate was
significantly better
with intramuscular
progesterone
(40.9% vs 18.1%; p
0.004).
Oral
progesteron
e (600 mg/
day
Intramuscular
progesteron
e (50
mg/day)
Licciardi et al. (1999)
Fertil Steril 1999; 71: 614–
18.
Only 43 patients
randomized,
terminated early for
ethical reasons.
No difference in CPR
and Implantation
rates in the 2 groups.
Oral
progesteron
e
IM
progesteron
e
Akira et al (2008)
Arch Gynecol Obstet
2008 277: 319-324, 40
patients
Clinical pregnancy
rates
(20 versus 25%)
Implantation rates
(9.1 versus 12.7%)
Oral
chlormadin
on acetate
600mg daily
50 mg i.m.
progesteron
e.
Iwase et al (2008)
Arch Gynecol Obstet 2008;
277:319–324.
prospective study 40
patients
25. LUTEAL PHASE SUPPORT IN IVF
Progesterone (oral route)
➢ Conclusions
Oral dydrogesterone is effective drug, well
tolerated and accepted among patients and
can be considered for routine luteal support.
Oral dydrogesterone versus vaginal progesterone
gel in the luteal phase support: randomized
controlled trial
VlatkaTomicab JozoTomica Djurdj ZigmundovacKlaicb MiroKasumC KrunoslavKunaa
European Journal of Obstetrics & Gynecology and Reproductive Biology
Volume 186, March 2015, Pages 49-53
26. LUTEAL PHASE SUPPORT IN IVF
Progesterone (oral route)
➢ Conclusions
Oral dydrogesterone seems to be as effective
as vaginal progesterone for LPS in ART cycles,
and appears to be better tolerated .
27. LUTEAL PHASE SUPPORT IN IVF
Progesterone (oral route)
luteal phase support should be given
via the intramuscular or vaginal
routes.
28. LUTEAL PHASE SUPPORT IN IVF
Progesterone (IM route)
P4 in oil base
Effective
Reliable and consistent plasma levels of P4
Rapidly absorbed in 2-8 hours
P4 levels are maintained for 72 hours
29. LUTEAL PHASE SUPPORT IN IVF
Progesterone (IM route)
➢ Weak compliance:
➢ Painful injections (long, thick needles)
➢ Inflammatory reactions
➢ Rash
➢ Needs to be administered by nurse
➢ Occasional sterile abscess
➢ Occasional allergic reaction (oil vehicle)
➢ Acute eosinophilic pneumonia associated with
IM administration of progesterone as luteal
phase support after IVF: 5 case reports
Bouckaert et al. Human Reproduction 2004
30. LUTEAL PHASE SUPPORT IN IVF
Progesterone (Vaginal route)
➢ Target organ delivery
➢ High concentration in uterus and endometrium
➢ First uterine pass effect
➢ Good patient compliance:
➢ Minimal systemic side effects
➢ Self administered
➢ Gel or capsules are equally effective
(Daya & Grundy, 2004)
31. LUTEAL PHASE SUPPORT IN IVF
Progesterone (Rectal route)
➢ Rectal application resulted in serum
concentration during the first 8 h twice as high as
other forms.
(Chakmakijan & Zachariah, 1987)
➢ Good patient compliance
➢ No adequate studies
32. LUTEAL PHASE SUPPORT IN IVF
Progesterone (SC route)
➢ A new water-soluble progesterone
➢ Implantation rate, PR, LBR and early miscarriage
rate for Prolutex were similar to those for Crinone.
➢ The adverse event profiles were similar and
Prolutex was safe and well tolerated.
34. LUTEAL PHASE SUPPORT IN IVF
Progesterone (Vaginal versus IM routes)
IM progesterone is associated with the highest serum levels.
Vaginal progesterone increases endometrial tissue levels.
35. LUTEAL PHASE SUPPORT IN IVF
Progesterone (Vaginal versus IM routes)
OutcomeComparisonStudy
The ongoing CPR
comparably high, with
31% in the Crinone A
8% group vs. 22%
Vaginal
Crinone
A8% twice
daily
IM
progeste
rone 100
mg daily
Gibbons et al. Fertil
Steril 1998; 69: 96–101.
Higher pregnancies
(%) 45.7% vs. 30.6 %
Clinical pregnancies
(%) 34.3 % vs. 19.1 %
Ongoing pregnancies
28.9% vs. 11.0 %
Live births 22.1% vs.
8.0%
Vginal
progester
one gel,
90 mg
(N=52)
IM
progeste
rone50
mg
(N=52)
Abate et al. (1999)
Clin Exp Obstet Gynecol 1999;
16: 203–6.
A prospective, double-
blind, randomized,
tubal factor infertility
36. LUTEAL PHASE SUPPORT IN IVF
Progesterone (Vaginal versus IM routes)
➢ .
OutcomeComparisonStudy
The LBR per ET 50% vs.
53.5% Comparable
Majority preferred
vaginal progesterone;
(easier, (69.2%), less
painful (76.9%) and
less time-consuming
(61.5%).
Vaginal Progesterone
Versus
IM Progesterone
Damario et al.(1999)
Fertil steril
1999;72:830-6
The group given vaginal
progesterone had
previously significantly
more IVF attempts and
had longer stimulation.
The ongoing clinical
pregnancies was
similar between
groups – 34.9% VS.
32%
Vaginal progesterone
(Crinone 8%; 90 mg)
(N=100) Versus
IM progesterone, 50 mg
(N=106)
Chantilis et al. (1999)
Fertil Steril 1999
Prospective study with
a historical control
group
Pregnancy rates of
25.7% (19/74) VS.
29.5% (18/61)
Comparable
Vaginal Crinone A 8%
(N=61)
Versus
50-100 mg IM progesterone
(N=74)
Bieber et al. (1998)
Fertil Steril 1998; 70 (Suppl
1) Retrospective study
37. LUTEAL PHASE SUPPORT IN IVF
Progesterone (Vaginal versus IM routes)
In a metanalysis on 5 studies
Artini et al. 1995,
Perino et al. 1997,
Abate et al. 1999,
Anserini et al. 2001,
Guesa et al. 20001)
➢ OPR and SAB were not different.
Pritts & Atwood, Hum Reprod. 2002
38. LUTEAL PHASE SUPPORT IN IVF
Is it beneficial to add estrogen to
progesterone for LPS ?
39. LUTEAL PHASE SUPPORT IN IVF
Is it beneficial to add estrogen for LPS ?
OutcomeComparisonStudy
The pregnancy
rates recorded in
both groups were
identical – 29%
No estrogen Versus
supplementation with
6 mg estradiol valerate
with 600 mg vaginal
progesterone daily.
Smitz et al. (1993)
Hum Reprod (1993) 8:40–45
Prospective Randomized
extensive study, 378
patients.
Pregnancy rates
per ET (28.0%
vs.26.5%
Birth rates per P
(78.6% vs. 76.1%
2 mg estradiol valerate
daily or no
supplementation after
with 50 mg
progesterone im. daily.
Lewin et al. (1994)
Fertil Steril 1994; 62: 121–5.
Prospective randomized
study, 100 consecutive
patients
? Better
Implantation rate
with estrogen
supplementation
Addition of estrogen to
a standard
progesterone LPS vs.
no estrogen
Pritts & Atwood (2002)
Human Reproduction, 2002;17,
2287-2299.
A meta-analysis of the
randomized trials
40. LUTEAL PHASE SUPPORT IN IVF
Is it beneficial to add estrogen for LPS ?
OutcomeComparisonStudy
Significantly higher PR
E2 supplementation (PR
32.8 versus 23.1%). The
best pregnancy results
were with high dose E2
supplementation (PR
51.3%).
evaluated the effect
of different E2
supplementation
doses (0, 2, or 6 mg)
in agonist cycles (n =
231). compared with
no E2 substitution
Lukaszuk et al. (2005)
Fertil Steril (2005) 83:1372–
1376
Prospective
randomized study
Highest pregnancy rate
was achieved in group
C (45.56%), Addition of
6 mg E(2) valerate to P
support may encumber
the sharp decline in
luteal E(2) level.
On embryo transfer
day, only P (group A,
n = 90), P along with 6
mg E(2) valerate
either orally (group B,
n = 90), or vaginally
(group C, n = 90) for
luteal support.
Elgindy et al., Fertil
Steril, Fertil Steril
(2010) 1;93(7):2182-8.
41. LUTEAL PHASE SUPPORT IN IVF
Is it beneficial to add estrogen for LPS ?
Ludwig & Diedrich (2001)
Acta Obstetricia et Gynecologica Scandinavica
Controversy surrounds the benefits
derived from supplementation of
estrogen for luteal support.
Supplementary administration of
estradiol for luteal phase support
appears unnecessary, although the
data are inconsistent.
Further studies would undoubtedly be
worthwhile to more thoroughly
investigate this approach.
.
42. LUTEAL PHASE SUPPORT IN IVF
Is it beneficial to add estrogen for LPS ?
Kolibianakis et al. (2008) Hum Reprod
Four RCTs (n=587 patients)
CONCLUSIONS:
The currently available evidence
suggests that the addition of estrogen
to progesterone for luteal phase
support does not increase the
probability of pregnancy in IVF.
43. LUTEAL PHASE SUPPORT IN IVF
Is it beneficial to add estrogen for LPS ?
Gelbaya et al. (2008) Fertil Steril. 2008
Ten RCTs used Progesterone alone or
combined with estradiol valerate for LPS
The addition of E(2) to P for LPS has no
beneficial effect on pregnancy rates.
The data in the literature are limited and
heterogeneous.
A large multicenter, properly designed RCT
is needed to further clarify the role of luteal
E(2) supplementation in IVF
44. LUTEAL PHASE SUPPORT IN IVF
Is it beneficial to add estrogen for LPS ?
van der Linden et al. (2011)
Cochrane Database Syst Rev
Overall, the addition of other substances
such as estrogen or hCG did not seem to
improve outcomes
Huang et al., Fertil Steril. 2015
The best available evidence suggests that
E(2) addition during the luteal phase does
not improve IVF/ICSI outcomes through oral
medication, even with different daily doses.
Furthermore, RCTs that study other
administration routes are needed.
45. LUTEAL PHASE SUPPORT IN IVF
GnRHa in midluteal phase
GnRH receptor is expressed in the human
preimplantation embryos, endometrium,
corpus luteum
GnRHa has been shown to stimulate
trophoblast production of hCG
Studies:
Increased LBR
(Kyrou et al., 2008)
GnRHa Vs no tt GnRHa is beneficial
(Glujovsky et al., 2010)
Effective
(van der Linden et al., 2012)
46. LUTEAL PHASE SUPPORT IN IVF
GnRHa in midluteal phase
Martins et al., Ultrasound Obstet Gynecol. 2015
Metanalysis of 10 studies examining 3,056
women
There is evidence that adding GnRH
agonist during luteal phase improves
ongoing pregnancy.
However, this evidence is of very low quality
and there is no evidence about adverse
perinatal outcomes and congenital
malformations.
We therefore believe that including this
intervention on clinical practice would be
still premature
48. LUTEAL PHASE SUPPORT IN IVF
For how long should LPS continue after IVF ?
➢ The date of initiation and discontinuation of
supplemented hormones are not adequately
studied in the literature.
➢ Optimal progesterone supplementation
should begin on the day of oocyte retrieval or
1 day later – before embryo transfer on day 2.
➢ The luteo-placental shift, does not take place
until about the 8th–10th week of pregnancy.
49. LUTEAL PHASE SUPPORT IN IVF
For how long should LPS continue after IVF ?
OutcomeComparisonStudy
Biochemical
pregnancy: 23% vs
18%
Ectopic pregnancy: 5
vs. 7 Abortion 11.5% vs
15%
Delivery rate. 63% vs.
64%
All similar.
200 pregnant women received
progesterone (control group)
and 200 pregnant women
received none (study group)
For three weeks after a positive
hCG test,
Schmidt et al.
(2001)
Fertil Steril (2001)
75:337–341
Delivery rate.
118 (78.7%) versus 126
(82.4%)
Not significant.
(n = 150) withdrew vaginal
progesterone from the day of
positive hCG
Versus (n = 153) continued
vaginal progesterone for 3
weeks of pregnancy
Nyboe et al.
(2002)
Hum Reprod (2002)
17:357–361
Similar on going PR
and bleeding
episodes in the two
groups.
Randomized 257 pregnant
patients after ICSI into either to
stop LPS on the day of US or to
continue for 3 weeks.
Aboulghar et al.
2008,
Human Reprod. 2008;
23:857-862
50. LUTEAL PHASE SUPPORT IN IVF
For how long should LPS continue after IVF ?
➢ The data provided from these studies did not
support traditional duration of LPS.
52. LUTEAL PHASE SUPPORT IN IVF
CONCLUSION
➢ Is LPS of benefit for IVF patients?
➢ What is the best dose and formulations of
drugs for LPS ?
➢ Which Is superior for LPS hCG or
Progesterone?
➢ Which is the best route for administration of
progesterone for LPS ?
➢ Is it beneficial to add estrogen to
progesterone for LPS ?
➢ What are other hormones that can be
used?
➢ For how long should LPS continue after IVF ?
54. LUTEAL PHASE SUPPORT IN IVF
CONCLUSION
What is the best dose and formulations of drugs
for LPS ?
➢ Progesterone is first choice for LPS.
➢ I.M. and vaginal progesterone are equally
effective, but most patients will prefer vaginal
progesterone administration.
➢ Oral progesterone is clearly inferior to i.m. or
vaginal
55. LUTEAL PHASE SUPPORT IN IVF
CONCLUSION
What is the best dose and formulations of drugs
for LPS ?
➢ The optimal dose of progesterone has not
been studied in a scientific way in the
literature.
➢ No evidence to support co-tt to progesterone
including aspirin, heparin, viagra….apart from
midluteal phase GnRHa which seems
promising but needs further evaluation.
56. LUTEAL PHASE SUPPORT IN IVF
CONCLUSION
Is it beneficial to add estrogen to progesterone
for LPS ?
The administration of estrogen for LPS is
probably not beneficial,
Although a definitive conclusion can not be
drawn due to the controversial nature of the
data available.
57. LUTEAL PHASE SUPPORT IN IVF
CONCLUSION
For how long should LPS continue after IVF ?
➢ Progesterone supplementation should begin
on the day of oocyte retrieval or 1 day later –
before embryo transfer on day 2.
➢ Recent data available does not support the
extension of LPS to 8-10 weeks gestation.